Click on the type of cancer you would like to know more about.
The reader of this guide may feel very, very confused and challenged with this information. It obviously is different from the 'sound bites' that are often published on PSA screening. Unfortunately, while sound bites and simple rules are appealing, in this case they're simply wrong and can provide misleading information. It has been our experience, however, that providing this information in a balanced fashion can help a man make an individualized decision. It has been rewarding to us to watch as men use this information to make a decision that 'feels right'. For example, we have seen two men with precisely the same PSA and with similar prostate cancer risks, examine the complex choices, weighing the reasons to have a biopsy with the reasons why not to have a biopsy. These two men with very similar risks then come to completely opposite decisions: one man chooses to have a biopsy and the other chooses to repeat his PSA in a year and to defer a decision until then. Both men take into account intangible issues that the physician cannot know. For some men, sexual function may be an important priority; for others, it may not. One man for whom prostate cancer is a special concern (perhaps his golf partner passed away from the disease) may decide to have a biopsy. There may be other issues that a man simply cannot put his finger on. Regardless, it is a very personal decision for which the medical literature cannot give a single recommendation.
For some men, reading up on screening, prostate cancer and its treatment, in combination with using the PCPT Prostate Cancer Risk Calculator may be all that is required to make an informed decision. For other men, the complexity of the decision may be overwhelming. For anyone who is struggling with how to interpret his PSA or whether to consider a prostate biopsy, serious consideration should be given to making an consultation appointment with a subject matter expert, a person who understands prostate cancer, screening, screening tests, prostate cancer treatment, and informed decision making. National Cancer Institute-designated Cancer Centers can often provide guidance on whom to see. Members of the Society of Urologic Oncology are experts in this field. The members of the Multidisciplinary Genitourinary Cancer Clinic here at UT Health Science Center in San Antonio are also subject matter experts, having led many of the breakthroughs in this field. Here at UTHSCSA, we have been using the Risk Calculator since its inception and are among the leadership in not only helping patients and physicians understand its use but in making the calculator better. For an appointment with members of the Clinic (Drs. Ian Thompson, Dipen Parekh, Sunil Sudarshan, or Jamey Sarvis), a phone call to 210-450-9600 is all that is necessary.
We here at UTHSCSA feel that all patients are individuals and, when it comes to prostate cancer early detection, when so many factors are involved in the decision-making, no two men will reach the same conclusion. We believe that an individualized approach to screening is mandatory.
A discussion of the current state of the science regarding finasteride, dutasteride, and prostate cancer prevention. This discussion is provided for patients by Ian Thompson, MD, Director of the Cancer Therapy and Research Center, Professor of Urology, UT Health Science Center San Antonio. The opinions stated are those of Dr. Thompson and do not constitute those of the CTRC, UTHSCSA, UT System, nor the National Cancer Institute. Effective date of this information: July 3, 2011.
How can I prevent prostate cancer? This is an important question. Let's think first about the statistics.
So, a primary concern for a US man should be how to avoid getting prostate cancer in the first place. Why should this be of concern? While treatment is exceptionally effective in controlling the cancer if it's found, these treatments do have side effects including problems with erections, urinary problems including obstruction and leakage (urinary incontinence), as well as bowel complications. In a few men, more significant complications can occur.
For most men, never having prostate cancer in the first place, is far better than regular testing, biopsies, facing a diagnosis, treating the disease, and taking care of the side effects of treatment as well as a lifetime concern about cancer recurrence. As a result, most men are interested in exploring possible ways to prevent prostate cancer.
The list of possible preventive strategies for prostate cancer is extremely lengthy. Most of these preventive strategies come from studies of men with and without prostate cancer, looking for hints to what might have kept the men without cancer from developing this disease. Unfortunately, most people don't understand that these types of studies only give doctors hints, not evidence that the strategy works. In fact, using these types of studies, sometimes the hints not only didn't pan out when tested but actually increased the risk of cancer. A tragic example of this was the observation made for years that people who smoked but ate more Vitamin A in their diet had a lower risk of lung cancer. For years, recommendations were made for smokers to increase their Vitamin A to reduce their cancer risk. When this strategy was actually tested by the National Cancer Institute in an enormous study of smokers, half who received Vitamin A and half received an inactive pill, the smokers who took Vitamin A had a higher risk of lung cancer. Fortunately, this study was done and now doctors tell their patients who smoke not to take Vitamin A. In the case of vitamins and supplements for prostate cancer, the National Cancer Institute sponsored a study of more than 35,000 men to determine if the two most promising substances, vitamin E and selenium, could reduce a man's risk of prostate cancer. The final result was that neither reduced prostate cancer risk and that there was a slight increase in prostate cancer risk with vitamin E.
As a result, the reader of this should be aware that while there are many hints as to strategies that might reduce a man's risk of prostate cancer, at this time there is only one strategy that has been proven to reduce a man's risk of getting prostate cancer. This proof came from the 18,882-man Prostate Cancer Prevention Trial, a study sponsored by the National Cancer Institute. The PCPT began in 1993, testing the targeted drug finasteride (Proscar) which had recently been approved by the US Food and Drug Administration for the treatment of prostate enlargement symptoms. The drug targets an enzyme present in the scalp and in the prostate, reducing male hormone levels in these two locations. (In the scalp, the effect is to increase hair growth; finasteride is sold for this purpose as Propecia.)
The PCPT enrolled cancer-free men and followed them for 7 years. Half took finasteride, half took an inactive agent. The men were followed annually with PSA tests and prostate examinations (physician examination of the prostate, known also as a digital rectal examination or DRE). If either were abnormal during these yearly checks, a prostate biopsy was recommended. For men without prostate cancer after 7 years of participation, a biopsy was recommended.
Fifteen months prior to the anticipated closure of the study, the independent monitoring board of the study recommended closure due to overwhelming evidence that finasteride reduced a man's risk of prostate cancer. The reduction in risk was 24.8% for men who took the drug. At that time, to provide the study's results as quickly as possible, the results as they were known at that time were published. The result at that time included not just the significant reduction in risk of cancer but also the increase in risk of a much less common but more aggressive tumor in the group of men who took finasteride. An accompanying editorial with the article in New England Journal of Medicine, written by Dr. Peter Scardino of Memorial Sloan Kettering Cancer Center, took most of the enthusiasm away from the use of this medication to reduce the risk of prostate cancer because of the possibility that the drug may have increased the risk of more aggressive cancers.
That was the way things stood in 2003.
Since that time, the study's leadership and scientists continued to examine the study's results. A series of unexpected findings were encountered. In chronological order, they were:
The most recent two analyses from the study's scientists were published electronically concurrently with a keynote address by Dr. Ian Thompson at the Annual Meeting of the American Urological Association on May 18, 2008 in Orlando, Florida. The two studies answered the two lingering questions about the results of the PCPT. A group of scientists from across the United States including statisticians from the Fred Hutchinson Cancer Research Center calculated that actual impact of finasteride on cancer risk as well as the impact on aggressive cancer risk. These final results were: (a) A 30 percent reduction in the risk of prostate cancer and, even more importantly, (b) a 28 percent reduction in the risk of aggressive prostate cancer. Several other independent groups have analyzed the PCPT data and found similar results.
It is important to understand that the definition of aggressive cancer in the PCPT was Gleason 7-10 cancers. (The Gleason scoring system is the one used to determine a cancer's aggressiveness.) The higher the Gleason score, the more aggressive the tumor. The majority of Gleason 7-10 tumors are Gleason 7. In the most recent study of its kind (the vitamin E and selenium study), Gleason 2-6 tumors were about 63%, Gleason 7 was about 30%, and Gleason 8-10 was about 7% of all tumors. The PCPT showed very clearly that these most common cancers, the Gleason 2-6 tumors, were significantly less in men taking finasteride. Using the PCPT definition of aggressive cancers, cancers that are almost always treated with surgery or radiation in the U.S., as was noted above, when we account for the improved detection of these tumors, there was about a 28% reduction. The group of tumors for which we cannot be certain, the Gleason 8-10 tumors, may have been increased. Unfortunately, because these are so uncommon, the accuracy of this observation is uncertain: were they increased because they develop or grow faster in men receiving finasteride or were they simply more easily found due to improved PSA testing and better biopsy? The answer is not known nor can it be known: the PCPT was not designed to answer this question for this very small group of men with prostate cancer.
The second analysis asked the question as to whether the cancers that were prevented in the PCPT were cancers that posed men a risk of spread and complications of cancer. (Some had argued that the tumors detected in the PCPT because the PSA levels were lower than in many previous studies, were small and unimportant.) What actually turned out was that about 75% of the cancers met the Johns Hopkins' criteria of 'significance'. This is roughly the same rate of significant cancers as had been published in series of men undergoing surgery for prostate cancer. The bottom line: the cancers that finasteride prevents are the cancers for which most cancer surgeons recommend aggressive, radical treatment.
More recently, a 'sister' medication to finasteride – dutasteride (or Avodart) – was tested for its ability to reduce a man's risk of prostate cancer. In this study, known as REDUCE, dutasteride was administered to men with an elevated PSA and a greater risk of prostate cancer. The final results of the study were quite similar to the PCPT – a 22% reduction in risk of prostate cancer. Unlike PCPT, in the Gleason 7-10 tumors, there appeared to be no increase in risk. Again, looking at the much smaller group of men with Gleason 8-10 tumors, at the 4-year mark, there was an increase in this particular group of tumors.
With these findings, the American Urological Association and the American Society of Clinical Oncology, the two professional medical organizations that treat this disease, have recommended that men who are undergoing regular testing for prostate cancer be informed that finasteride is available for prevention of prostate cancer. They also recommend that men be informed of the risks and benefits.
At the time the PCPT was completed, finasteride was a generic medication and no plan was made to take this medication to the FDA for an 'indication' for prostate cancer prevention. At the present time, many companies make this medication. On the other hand, when REDUCE was completed, dutasteride (as Avodart) was made by one company and this company did request for an indication for prostate cancer prevention to the FDA. As this request was being compiled, the FDA requested that Merck & Co, the original makers of finasteride, provide information during the same hearing in early December 2010.
At this hearing, REDUCE information regarding dutasteride was presented by the company and their physicians while finasteride information was presented by the group of scientists and physicians sponsored by the National Cancer Institute on behalf of the Southwest Oncology Group. At that time, Merck & Co did not seek an indication for prostate cancer prevention from the FDA. The FDA panel reached the conclusion that neither medication should be labeled for this purpose out of concern for the risk of high grade disease. Subsequently, the FDA reached the conclusion that the label, which already included the high-grade cancer observation and which did not have any information on the significantly reduced prostate cancer risk, should have an augmented piece of information regarding the risk of high-grade cancer.
The scientific group from SWOG, representing the National Cancer Institute's Cooperative Group that had conducted the PCPT, was disappointed by these results and many in the US medical community were surprised. Further studies are ongoing to explore the effectiveness of both of these agents.
It is Dr. Thompson's opinion that patients should be made aware of the following information. (Note that this is Dr. Thompson's view and does not represent the view of the CTRC, the University of Texas Health Science Center at San Antonio, the National Cancer Institute, nor SWOG.)
1. A man in the US has a 16% risk of prostate cancer in his lifetime. If he is having PSA testing, that risk is probably at least 25% or 1 in 4.
2. If diagnosed with prostate cancer, a man has a 90% or greater likelihood of being treated with surgery (risk of impotence and incontinence), radiation (risk of impotence, urinary obstruction, bowel problems, and risk of other cancers induced by radiation), or hormonal therapy (risk of impotence, loss of sexual drive, osteoporosis, no energy, diabetes, and heart disease).
3. A five alpha reductase inhibitor (specifically, in this case, finasteride) will reduce a man's risk of prostate cancer by at least 25%. The true risk reduction is more likely to be about 30% as the medication helps to detect cancer, overall.
4. Finasteride reduces a man's risk of prostate enlargement problems. These problems can result in difficulty emptying the bladder, frequent urination, inability to urinate, and surgery for prostate enlargement.
5. Finasteride improves PSA testing, prostate examination by the physician, and prostate biopsy for detection of prostate cancer. It likely reduces the number of unnecessary biopsies (biopsies in men who do not have cancer).
6. Finasteride improves detection of aggressive cancers. These cancers are often missed during routine testing either because the PSA is not 'elevated', the prostate examination is normal, or the prostate biopsy misses the aggressive cancer.
7. Finasteride is associated with a risk of sexual problems including reduction in volume of ejaculate, decreased sex drive, and problems with erections. Should any of these problems occur, they generally disappear by stopping the medication.
8. Finasteride increases a man's risk of breast swelling or pain by about 1-2%.
9. Finasteride may increase a man's risk of the most aggressive cancers which constitute about 6-7% of all prostate cancers. This may be due to the medication causing these cancers to develop or grow or due to an improved detection of these cancers. This is a two-sided issue. On one hand, there is the potential that a small number of aggressive cancers are caused by finasteride. On the other hand, the medication will help to detect existing aggressive cancers that are missed if a man is not taking finasteride. This is a real issue as many as a third of men with cancer who are undergoing regular PSA testing have their cancers detected after the cancer has already spread beyond the prostate.
Dr. Thompson's conclusions are that a man should be given the opportunity to make up his own mind whether to use finasteride to reduce his risk of prostate cancer. There is some additional guidance that can be helpful. For some men, their risk of prostate cancer is so low that finasteride will have a low likelihood of preventing prostate cancer. A man, for example, whose PSA is below 1.0 ng/mL has a low risk of prostate cancer over the next 10 years – for him, finasteride will be less beneficial than a man, for example, with a PSA of 2.5 ng/mL. Also, a man who has problems from prostate enlargement (getting up at night to urinate, frequent urination, slow stream) would be more likely to benefit from finasteride as he would get both the reduction in prostate cancer risk as well as improvement in urinary symptoms as well as reduction in risk of complications from prostate enlargement.
Q: What are the side effects of finasteride if I use it for cancer prevention?
A: In general, there are two kinds of side effects of finasteride. One may be a side effect that is undesirable, the other may be desirable.
Undesirable side effects are generally of two types. The first is a 1-2% risk of swelling or tenderness of the breasts. The second side effect is related to sexual function. During the course of the study, there were more men who decided to stop, permanently or temporarily, their medication if they were taking finasteride. On the other hand, when experts examined the sexual function questionnaires that men completed during the study, they did find a slight increase in the rate of problems with sexual function (erections or sexual drive), the magnitude of the impact was clinically insignificant.
The desirable side effects of finasteride had been predicted when the study started. Because the drug was used extensively for treatment of prostate enlargement, the PCPT confirmed the benefit for prostate-related conditions. Urinary problems related to the prostate were reduced (these problems generally include a slow stream, urinary frequency, urgency, and getting up at night to urinate) as were surgical procedures for prostate enlargement. Inflammation of the prostate was reduced, the risk of the sudden inability to urinate due to prostate enlargement was reduced, and urinary tract infections were also less common with finasteride.
In the 18,882 men in the study, there appeared to be no other side effects (such as cancer, heart disease, or other important medical conditions) with finasteride.
Q: Who should consider taking finasteride for prostate cancer prevention?
A: Because the PCPT was the first study to include a biopsy in all men, regardless of their PSA level, study investigators were able to develop a tool to help predict the likelihood that cancer was present based on several risk factors (age, race/ethnicity, PSA, DRE findings, family history, and any history of a previous prostate biopsy). (This tool is available at the Department of Urology web site at UTHSCSA: http://deb.uthscsa.edu/URORiskCalc/Pages/uroriskcalc.jsp). The PCPT scientists then used this tool to examine how a man’s risk for prostate cancer affected the degree of benefit from finasteride. Interestingly, regardless of baseline risk of prostate cancer, all men seem to achieve about the same 25-30% benefit from finasteride. For example, a 55 year old man with no family history of prostate cancer and with a PSA of 0.5 ng/mL has about the same 25% reduction in risk of prostate cancer as the 70 year old man with a PSA of 2.5 ng/mL. While both men achieve the same percent benefit, the number of men like the 55 year old who would have to take finasteride to prevent one case of prostate cancer would be more (about 45 or so) than the number of men like the 75 year old (about 14) who would have to take finasteride to prevent one case of prostate cancer. It’s actually quite similar to other prevention strategies. A careful driver probably has a lower likelihood of benefitting from wearing a seatbelt than a risk-taking, aggressive driver. Similarly, a young marathon runner with an elevated cholesterol has a lower risk of a heart attack than a sedentary, overweight person with an elevated cholesterol. For both these groups, they may choose to wear seatbelts or alter their diet or take medications to lower their cholesterol. It must be emphasized, however, that it would appear from the design of the PCPT, that the conclusion of a reduction in prostate cancer risk might only be seen in men who have chosen to have regular PSA screening. It is unknown how finasteride may affect the risk of prostate cancer in a man who does not undergo regular screening.
Q: Finasteride is not approved [the proper term is actually ‘registered’] by the Food and Drug Administration for prostate cancer prevention. Can my doctor prescribe it for me?
A: Finasteride is registered with the FDA for the treatment of symptoms related to prostatic enlargement. If a patient has those symptoms he may be given finasteride by his physician. If a man desires the drug only for prevention, his physician can still prescribe the medication. Whether or not the prescription drug coverage of the patient will pay for the drug would depend on the insurance.
Q: I’ve noticed that there is another drug like finasteride available as well. Will it have the same preventive effect as finasteride?
A: The other drug like finasteride is called dutasteride and is currently marketed as Avodart. It, like finasteride, is used for prostate enlargement symptoms. Whether it would have the same effect as finasteride is not known. Dutasteride is currently being tested in a smaller study than the PCPT to determine if it as well has a preventive effect. That study is testing whether dutasteride, given to men with a PSA of 2.5 or greater and who have had a prostate biopsy that is negative for cancer, will reduce the risk of cancer on two subsequent biopsies, one 2 years later and one 4 years later. The results of that trial should be available in mid-2009.
Q: I don’t like prescription drugs and prefer ‘natural’ alternatives for prostate cancer prevention. Are there any of these approaches that are proven?
A: Unfortunately, no. There are many, many supplements and dietary products for which preliminary evidence suggests a possible preventive effect. None of these are proven. Two of these – selenium and vitamin E – are currently being tested in a very large, National Cancer Institute-sponsored study. The list of other supplements and agents that has been linked with prostate cancer prevention is almost endless. Unfortunately, none of these have been tested. As a result, if a man takes such a supplement, like all other unproven medical strategies, we simply don’t know whether it will work.
It is also important to understand that with unproven strategies for prostate cancer prevention, there are three questions that need to be addressed:
Many people will claim that supplements and natural products simply cannot do these things. Evidence from prior experience suggests otherwise. With regards to cancer, the Vitamin A story (an actual increase in lung cancer with Vitamin A) is a sad example. With regards to other disease, recent studies finding an increased risk of congestive heart failure in patients with heart disease who received Vitamin E is an example. Finally, the experience with a prostate cancer drug – PC SPES – that was associated with an increase
Q: Who sponsored the Prostate Cancer Prevention Trial? Was it a drug company study?
A: No. The Division of Cancer Prevention of the National Cancer Institute sponsored the PCPT. The study was administered by the Southwest Oncology Group, a large collaboration of community and academic health centers across the U.S. The company that originally developed finasteride, Merck & Co, provided the pills to the Southwest Oncology Group and National Cancer Institute for the study.
Q: If I am interested in a consultation regarding prostate cancer prevention to determine what steps I could personally take to reduce my risk of cancer, who should I see?
A: Prostate cancer is a very complex disease; this, in combination with the complexity of cancer prevention would suggest that a patient interested in prostate cancer prevention should see a subject matter expert in the field. National Cancer Institute-designated Cancer Centers are a good place to seek a person with such an expertise. Members of the Society of Urologic Oncology are also a good source of information. For those individuals who would like to see Dr. Thompson who coordinated the Prostate Cancer Prevention Trial, appointments can be made directly with his offices. (210-450-1300) Other individuals on the faculty at UTHSCSA who are Urologic Oncologists who specialize in this area include Dr. Sunil Sudarshan as well as Dr. Dipen Parekh.
Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, Lieber MM, Cespedes RD, Atkins JN, Lippman SM, Carlin SM, Ryan A, Szczepanek CM, Crowley JJ, Coltman CA Jr. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003 Jul 17;349(3):215-24.
This is the landmark first publication of the results of the Prostate Cancer Prevention Trial in 2003. The study’s initial analysis showed a remarkable 24.8% reduction in prostate cancer risk with finasteride.
Thompson IM, Lucia MS, Redman MW, Darke A, La Rosa FG, Parnes HL, Lippman SM, Coltman CA. Finasteride decreases the risk of prostatic intraepithelial neoplasia. J Urol. 2007 Jul;178(1):107-9;
This analysis of the results of the Prostate Cancer Prevention Trial showed that finasteride reduced the risk of the development of high grade prostatic intraepithelial neoplasia, a pathologic condition of the prostate that is thought to be pre-malignant (it may turn into cancer over time). There was a significant reduction in the risk of this condition with finasteride.
Thompson IM, Tangen CM, Goodman PJ, Lucia MS, Parnes HL, Lippman SM, Coltman CA Jr. Finasteride improves the sensitivity of digital rectal examination for prostate cancer detection. J Urol. 2007 May;177(5):1749-52.
This analysis of the results of the Prostate Cancer Prevention Trial showed that finasteride improved a physician’s ability to detect prostate cancer when examining the prostate with a digital rectal examination. Remarkably, while improving the ability to detect cancer, it did not increase the risk of an unnecessary biopsy.
Lucia MS, Epstein JI, Goodman PJ, Darke AK, Reuter VE, Civantos F, Tangen CM, Parnes HL, Lippman SM, La Rosa FG, Kattan MW, Crawford ED, Ford LG, Coltman CA Jr, Thompson IM. Finasteride and high-grade prostate cancer in the Prostate Cancer Prevention Trial. J Natl Cancer Inst. 2007 Sep 19;99(18):1375-83.
This analysis, by a panel of some of the most skilled pathologists in the US, found that finasteride did not hamper a pathologist’s ability to analyze prostate biopsies but that it improved the ability to detect aggressive prostate cancer by biopsy. Presumably, this improved detection was due to the drug’s reduction of prostate volume, improving the ability of biopsy to properly sample the prostate.
Moinpour CM, Darke AK, Donaldson GW, Thompson IM Jr, Langley C, Ankerst DP, Patrick DL, Ware JE Jr, Ganz PA, Shumaker SA, Lippman SM, Coltman CA Jr. Longitudinal analysis of sexual function reported by men in the Prostate Cancer Prevention Trial. J Natl Cancer Inst. 2007 Jul 4;99(13):1025-35.
This analysis by a group of Quality of Life experts found that the impact of finasteride on sexual function was clinically insignificant. This was the first long-term analysis of the results on this drug on sexual function and included the largest number of men treated with this drug to date.
Thompson IM, Chi C, Ankerst DP, Goodman PJ, Tangen CM, Lippman SM, Lucia MS, Parnes HL, Coltman CA Jr. Effect of finasteride on the sensitivity of PSA for detecting prostate cancer. J Natl Cancer Inst. 2006 Aug 16;98(16):1128-33.
This analysis found that finasteride not only improved the ability of PSA to indicate the presence of prostate cancer but that finasteride improved the ability of PSA to indicate the presence of aggressive prostate cancer. Because aggressive prostate cancer can be found at lower levels of PSA and because it is generally acknowledged that aggressive prostate cancer is the type of cancer that needs to be found if screening is performed, this analysis suggests that finasteride may actually improve on the outcomes of prostate cancer screening (in addition to the overall reduction in risk of cancer).
Lippman SM, Goodman PJ, Klein EA, Parnes HL, Thompson IM Jr, Kristal AR, Santella RM, Probstfield JL, Moinpour CM, Albanes D, Taylor PR, Minasian LM, Hoque A, Thomas SM, Crowley JJ, Gaziano JM, Stanford JL, Cook ED, Fleshner NE, Lieber MM, Walther PJ, Khuri FR, Karp DD, Schwartz GG, Ford LG, Coltman CA Jr. Designing the Selenium and Vitamin E Cancer Prevention Trial (SELECT). J Natl Cancer Inst. 2005 Jan 19;97(2):94-102.
This is the most recent summary of the ongoing National Cancer Institute-sponsored prevention study that includes more than 35,000 men, testing both Vitamin E and Selenium to determine if these agents can reduce a man’s risk of prostate cancer.
Christopher J. Logothetis and Paul F. Schellhammer Cancer Prev Res 2008 1: 151-152.
This editorial, written by two of the world’s foremost physician experts in prostate cancer (Dr. Logothetis runs the prostate cancer program at MD Anderson Cancer Center and Dr. Schellhammer, an internationally respected Urologic Oncologist and Past-President of the American Urological Association) puts the results of the Prostate Cancer Prevention Trial into perspective, suggesting that physicians should seriously consider offering finasteride to their patients in order to reduce their risk of developing prostate cancer.
Finasteride Does Not Increase the Risk of High-Grade Prostate Cancer: A Bias-Adjusted Modeling Approach
Mary W. Redman, Catherine M. Tangen, Phyllis J. Goodman, M. Scott Lucia, Charles A. Coltman Jr., and Ian M. Thompson Cancer Prev Res 2008 1: 174-181.
This analysis of the Prostate Cancer Prevention Trial by a group of statisticians at the Fred Hutchinson Cancer Research Center in Seattle, Washington found that the actual reduction in risk of prostate cancer with finasteride was about 30% - for both all cancers as well as for aggressive cancer as well.
Pathologic Characteristics of Cancers Detected in the Prostate Cancer Prevention Trial: Implications for Prostate Cancer Detection and Chemoprevention
M. Scott Lucia, Amy K. Darke, Phyllis J. Goodman, Francisco G. La Rosa, Howard L. Parnes, Leslie G. Ford, Charles A. Coltman Jr., and Ian M. Thompson Cancer Prev Res 2008 1: 167-173.
This analysis of the Prostate Cancer Prevention Trial, led by the primary pathologist of the study, analyzing about 1600 individuals diagnosed with prostate cancer in the study, found that the types of cancers that were prevented by finasteride were essentially the same as those that are having surgery or radiation today.
Estimating Rates of True High-Grade Disease in the Prostate Cancer Prevention Trial
Paul Pinsky, Howard Parnes, and Leslie Ford Cancer Prev Res 2008 1: 182-186.
This independent analysis of the results of the Prostate Cancer Prevention Trial found that finasteride reduces not only the risk of prostate cancer overall but also the risk of aggressive cancers.
Radical prostatectomy, performed through a small incision just below the belly button, is called a radical retropubic prostatectomy. This procedure has dramatically changed since its first performance in the 1950’s. The procedure also differs significantly from one individual to another. What is described on this web page is the current experience of Dr. Ian Thompson, the Director of the Multidisciplinary GU Oncology Clinic at the CTRC of the UTHSCSA. The procedure is performed in essentially the same manner by Drs. Sunil Sudarshan, Dipen Parekh, and Jamey Sarvis.
Members of the GU CTRC Urology Clinic perform this procedure at Santa Rosa Northwest Hospital and at University Hospital. Several hundred radical prostatectomies are performed annually by UTHSCSA Urology physicians. About half to two-thirds are with this approach.What should a man expect with this procedure?
The hospital stay with a UTHSCSA radical retropubic prostatectomy is generally about 24 hours. Preparations for the procedure are extensive but are primarily focused on ensuring that the man and his family is well-informed and that this specific procedure is the best treatment for this individual man. A consultation with one of the UTHSCSA urology physicians includes a complete medical history, and examination, and then careful focus on the options regarding treatment. Treatment options for every man with clinically localized prostate cancer include active surveillance, radiation therapy, brachytherapy (radioactive seeds), and surgery. Careful counseling helps for men to decide which treatment is right for them.
The other preparation before the procedure involves laboratory testing which generally includes blood and urine testing, a chest x-ray as well as an EKG. For some men, other physicians will be consulted with the goal to ensure that the procedure is performed safely and with the lowest possible risk of complications.
Check in to the hospital is on the day of the procedure, generally about 2 hours before it is scheduled to begin. At that time, final checks of lab testing, changing into hospital clothing, and any last minute questions are answered. In the Operating Room, the procedure is generally performed with a general anesthesia (go to sleep) by the anesthesiologist. The incision for the procedure averages about 3 inches long (in some, it can be as short as 2 inches; if a man is significantly overweight, it can be 4 or 5 inches long). We have found it fascinating that many web sites state that the incision is about half the length of the abdomen; at least in our hands, we haven’t seen this type of incision for quite a while. The illustration below shows what the incision looks like.
For most men, the procedure involves only removing the prostate but if the tumor is an aggressive tumor, it may also include removal of the pelvic lymph nodes. These nodes can be the first spot of spread of prostate cancer and it is important to help decide on any subsequent treatment to know if tumor is present. For most men, however, the risk of lymph node involvement is so low that removing the lymph nodes is not necessary.
The procedure itself requires about 2 hours. Afterwards, the 3 inch skin incision is closed with a technique used often by plastic surgeons so that the stitches are all on the inside. As a result, no additional visits are required to have the stitches removed. A small drain tube is left overnight to allow any fluid present to escape. A catheter is also left in the bladder for about 7 days.
After about 1-2 hours in the Recovery Room, our patient goes to his room. Later that day, he will be up in a chair and then walking. Depending on his appetite, he may begin with water and juices that evening. By morning, he is usually having breakfast. It is our goal for our patients to be on their way home by between 10AM and 2PM of the day after surgery.
If our patients are from San Antonio, they are home the next day. As many of our patients come to our doctors from outside San Antonio (and often from outside Texas and from other countries), depending on the distance they have traveled, we often suggest that they stay in San Antonio for at least one additional night. We have a list of hotels that are close by which we can provide. Our physicians are available 24 hours afterwards so if there are any questions or problems, they are immediately available – by phone or in person.
At home for the week prior to the catheter removal, we encourage activity, primarily walking. Common sense is a good source of advice: start slowly and gradually increase activity. The reason we focus so much on getting back to being active is that it does many helpful things:
In general, after 7 or 8 days, we have our patients return to our clinic for a voiding trial. At that time, we fill the bladder with sterile water, and remove the catheter. This demonstrates that the man does indeed void well. During that very first urination after the prostate is removed, it also gives the man the opportunity to practice his Kegel’s exercises. As the urine is passing, midway, he can contract the muscle to ‘shut off’ the urinary stream. These are the exercises we recommend after surgery (and before surgery) to help speed the return of urinary control.
At that same visit, your physician will review the patient’s pathology report. In many men with locally-confined prostate cancer, we will recommend regular followup visits only. Some men, however, will have evidence of prostate cancer outside the prostate at the time of surgery. This finding does not indicate that the tumor isn’t cured – it simply means that there may be a higher risk of recurrence over the years to come. If present, we will discuss opportunities to reduce that risk including radiation therapy. Dr. Ian Thompson led the National Cancer Institute’s study that tested this treatment (beginning in 1987); this form of treatment was proven to dramatically reduce a man’s risk of cancer recurrence.
After a man returns home following surgery, we have some general recommendations.
Probably the most important factor in urinary control after a radical prostatectomy is the skill of the surgeon. It is important to do a good job of preserving the normal urethra, reconstructing the bladder neck, and joining the urethra back to the bladder. Nonetheless, immediately after surgery, there can be some initial urinary leakage. It is our goal to ensure that this urinary control comes back as quickly and as completely as possible.
Who is at a higher risk of urinary leakage afterwards? Individuals who are at higher risk include men who already had bladder problems to begin with. Individuals with nerve-related diseases like Parkinson’s disease or multiple sclerosis may have a bigger problem with return of urinary control. Men who are more overweight commonly seek their urinary control come back more slowly. Younger men note that their urinary control comes back more quickly than older men. For the vast majority of men, however, urinary control returns acceptably after surgery. In fact, it is extremely rare that additional treatments in our hands are needed for problems with urinary control. In fact, we (and others) have noticed that many men find that their urination is significantly better after surgery because the prostate (which previously caused them problems in emptying the bladder), has been removed. We are interested, however in speeding up urinary control.
What can be done to speed up the return of urinary control? The best thing that a man can do to hasten the return of normal urination is to work on his Kegel’s exercises. A Kegel’s exercise is simply the contraction of the muscle that helps to control urination. It can be thought of as the muscle that you would use if you suddenly had to stop mid-stream while you were urinating. The very best way to get the urinary control back the fastest is to learn how to do the exercises before the operation and to practice doing them. We generally recommend that you practice three times a day. Each time when you contract the muscle, do so for a count of 5, then relax. Repeat the exercise 10-15 times. After surgery, patients should resume the exercises after the catheter is removed and continue until urination is back to normal. The contraction of this muscle is very helpful if a man thinks he is going to sneeze, cough, or plans to stand up or lift something heavy; doing so reduces the risk of leaking a few drops of urine at that time.
Urinary function tends to return relatively quickly after surgery. While sexual function (normal erections) may return within a week or so after surgery, this is less common. For reasons that are not completely clear, the quality of erections after surgery appear to improve over time afterwards. We have seen patients whose erections continue to improve as many as 2 years after surgery.
It is important, however, for your physicians to do everything possible to help those erections return and to help them return as soon as possible after surgery. The best way to do so is to do a good nerve-sparing operation. It is for this reason that we specialize in this procedure at the UT Health Science Center’s CTRC. Our physicians have been actively doing these nerve-sparing operations on a regular basis using all of the different prostatectomy approaches for many years. (We do nerve-sparing robotic prostatectomies, retropubic prostatectomies, and perineal prostatectomies.) This is a meticulous technique that requires considerable experience.
With the advent of medications like Viagra, Levitra, and Cialis (these are called phosphodiesterase type 5 inhibitors or PDE5 inhibitors), Urologic Oncologists now have ways to do an even better job with return of sexual function after surgery. For some men, these medications are used after surgery to improve the quality of erections. (These medications do not ‘cause’ an erection; they facilitate an erection if a man is sexually stimulated.) We have as well used these medications in a manner similar to the way we use Kegel’s exercises to hasten the return of urinary function. Although the studies are incomplete in the medical literature, there is some evidence that beginning these medications on a regular basis after surgery speeds up the return of sexual function. As a result, for the man who is interested in speeding up the return of sexual function, we will generally begin these medications shortly after the operation, continuing them until the sexual function has return in a satisfactory manner. (Of interest, some men will choose to remain on these medications after surgery as they note that the quality of their erections, while acceptable without the medications, are simply better on a low dose of the medication.)
Going Home After Radical Retropubic Prostatectomy at UT Health Science Center at San Antonio
If you have had your radical retropubic prostatectomy at the UT Health Science Center at San Antonio, you have had the procedure performed by experts with this specific technique. (We have other experts with perineal prostatectomy as well as robotic prostatectomy. We have found with several decades of collective experience with these techniques that there is no one best treatment for prostate cancer and as a result, we can provide a range of treatments for our patients.) If you read on other Internet sites about recovery after radical prostatectomy, you may find different instructions than you will find here. This is simply because of the experience of our physicians at our institution.
Before we go any further, please understand that individual patients will have individual considerations. The descriptions here are for the majority of men who have had a radical retropubic prostatectomy. Specific considerations in some men may lead to differences in recommendations. If you are not certain, please be sure to call our 24-hour services to ask one of our physicians. You will also receive verbal and written instructions on discharge. This document is meant to provide general ideas about what it is like to go home after having your procedure performed by one of our surgeons.
For the majority of our patients, we will send them home the day after their surgery. In general, our patients will go home either after breakfast or after lunch. As a result, the stay in the hospital is approximately 24 hours.
At the time of discharge, you will receive written instructions regarding your followup visit at the clinic. In general, your followup visit for when the catheter is to be removed will be about 7-10 days after your operation. If you did not receive an appointment at the time of discharge or for some reason lost the paper with the date and time, please call us at 210-450-9600. We will be happy to verify it for you.
When you go home, you will have a small bandage on your incision. The stitches will usually all be on the inside so you can immediately take a shower; if you have staples on your incision, the nurse will review with you how to bathe with these. Soap and water is just fine for keeping clean.
You will also have a catheter in the bladder. It will be connected to a small drainage bag that you can wear on your leg. That bag generally holds 3-4 hours of urine, about as much as your bladder holds. There is a small valve at the bottom of it – simply twist the valve to empty the bag and then replace the lever back into position to shut off the valve. Unfortunately, this small bag doesn’t hold enough urine to last for the entire evening while you sleep so we will provide for you a larger bag that should hold 8-10 hours worth of urine. Connecting and disconnecting the bags is quite simple. The nurse will show you how before you go home. They do not screw together but simply pull to pull them apart and push them back together. This connection is generally quite stable so you do not need to push it too tight. You should also be provided with an elastic strap that goes on your leg to attach to the catheter. This keeps it from moving around too much and is primarily there for your convenience. You may also have some paper tape strips across the incision. If you do, they will usually fall off within a week or two. If they’re still there 2 weeks after the surgery, just pull them off yourself.
When you go home, we prefer that you do not drive until your catheter is removed. There is really no specific medical reason why you cannot drive (unless you are taking strong pain medications) but the catheter can serve as a distraction (like if you were talking on a cell phone) so it is safest if you don’t drive until the catheter’s been removed. In general, we tell our patients that they may return to driving after the catheter is removed. You might consider waiting a day or two after the catheter is removed to again keep from being ‘surprised’ as your urinary control is returning.
In terms of physical activity, we encourage walking when you go home. Walking keeps the blood in the legs circulating, helps you get up and become more active, reduces the risk of constipation and, as our patients have told us, generally just makes you feel better. We prefer that at least every hour or so, please get up and walk around. Going up and down stairs is OK but, just like everything, common sense prevails: if you are not certain what you can and cannot do, please call us and ask. Strenuous activity including lifting anything more than about 20 pounds should not be performed for 4 weeks after the surgery. At that time, we encourage gradual return to physical activity rather than trying to immediately go back to a 100% exercise level. It is our expectation, however, that our patients will return to all of the activities they were doing before the operation.
During the time that the catheter is in place, men often will notice that after they walk a distance, the urine may turn reddish tinged. (It takes only a drop of blood to turn a quart of water bright red.) If this happens, just sit down and drink fluids. The color should return to a clear or light yellow soon afterwards. Also, when you sit down to have a bowel movement, you may notice some rusty-colored fluid coming around the catheter. Don’t worry, this can happen and is of no specific concern.
At the time of discharge, we provide strong pain medications to our patients. Nevertheless, we have found that using our special techniques, most of our patients do not need these strong medications but can do just fine with one or two Advil (or other nonsteroidal anti-inflammatory medication) every 6 or 8 hours. The reason we prefer these types of medications is that, unlike the strong pain medications like Vicodin; Advil and other non-steroidal anti-inflammatory medications do not cause constipation. Another trick is to fill a sandwich baggie with ice or use a bag of frozen peas and just put them directly on the incision; this often helps any discomfort you have in that area.
We do encourage a diet full of fiber at the time of discharge. Constipation can be avoided by this, by increasing physical activity, drinking plenty of fluids such as water, as well as taking a stool softener we will provide for you.
When you return to have the catheter removed, we will generally fill the bladder and remove the catheter. At this time, our patients will have the first opportunity to contract the sphincter muscle to learn to better control the urine. We encourage learning to contract the muscle to develop the ability to stop and start urine flow. Once you have developed a good ability to stop and start the urine with the sphincter muscle, we encourage doing these exercises (called Kegel’s exercises) about three times daily. You should contract the muscle (in the same way you used to stop the urination) for a count of about 5-10 seconds, and then relax. Ten or fifteen repetitions are adequate. Do this three times daily. Patients will note that as they develop this muscle, they learn to contract the muscle just before an event that may cause urine leakage. Such events could be a sneeze or cough. They may also include standing up from a sitting position or lifting something heavy. After a while, the leakage generally disappears on its own but working on these exercises can help speed the return of urinary control.
The final aspect of returning to normal activity after surgery will be a discussion with your physician about sexual ‘rehabilitation’. There is growing evidence that the use of medications like Cialis, Levitra, or Viagra after surgery may speed up the return of erections. Generally, at the time of the visit when the catheter is removed, your physician will discuss with you the opportunity to use these medications on a scheduled basis with the goal to speed up the return of erections.
As with everything we discuss here in Urology, all aspects of cancer care and care of the Urology patient are individualized. If one of our patients has a problem or a question, we encourage a telephone call to us. The Urology Clinic at the MARC can be reached at 210-450-9600.
Our approach to prostate cancer prevention, detection, staging and treatment is highlighted by our multidisciplinary approach tailored towards an individual patient. Our focus is in delivering the state of the art care to all patients with prostate cancer while minimizing treatment related side effects. Our clinical expertise is complemented by a dedicated team of clinical and laboratory researchers who ensure the ready applicability and availability of the advancements made in the field of research to our patients in a safe and expedited manner.
The surgeon begins the robotic radical prostatectomy by making one incision (one centimeter, or less than half an inch, in length) around the navel in order to insert a thin, lighted tube with a telescopic camera on its tip (called a laparoscope) into the body. A harmless gas is introduced into the abdomen to create a space large enough to perform the surgery. Three or four small keyhole incisions are then made through which the robotic ports and instruments operate. The surgical DaVinci Robot is then attached to the ports. The operation is performed with specialized surgical instruments inserted, and the prostate (and, if necessary, lymph nodes and surrounding tissue) is removed. The surgeon has a complete control of the instruments with his fingers and foot pedals. Unlike conventional laparoscopic surgery, robotic surgery enables a surgeon with 3 –D vision, 12 times optical magnification and several degrees of motion that potentially translates into superior outcomes for the patients. The average time to perform a Robotic Radical Prostatectomy in our center is around 1.5- 2 hours.
Although it is not always possible due to the size and location of the cancer, one of the primary goals of radical prostatectomy is to be "nerve-sparing." This means that the surgeon preserves the web of tiny nerves that control erection and keeps them intact. This extremely delicate and precise technique is made possible with the laparoscopic approach because of the quality of the visualization of the surgical field, due to the magnification of the surgical area and reduced bleeding.
Some of the advantages of Robotic radical prostatectomy are:
Q : Why choose a surgeon from UTHSCSA ?
A : All the surgeons who perform Robotic surgery as well as Open surgery for Prostate as well as other urologic cancers at the UTHSCSA are Urologic Oncologists by training. The robotic surgeons at UTHSCSA have completed fellowships at Society of Urologic Oncology accredited institutions who are facile at Robotic as well as Open surgeries. Our have an established track record of achieving superior oncologic and quality of life outcomes in our patients who undergo surgery. It is important for some patients to select a physician who is not simply a technician but has the training and environment to serve as a comprehensive oncologic expert in the management of their disease. This may affect the choice of treatment itself, whether combination therapies should be included, and the opportunities to participate in advanced clinical trials, many of which are available from the National Cancer Institute through the CTRC, a National Cancer Institute-designated Cancer Center.
Q: Am I a Candidate for Robotic Prostate Surgery?
A : Almost all men who are candidates for the traditional, "open" radical prostatectomy are also candidates for a Robotic radical prostatectomy. The only exceptions are patients who have had extensive prior pelvic surgery or those who are not medically fit to undergo surgery.
Q: When does my catheter come out?
A: In most cases the catheter will come out 4-7 days after surgery at your first post-operative appointment.
Q: When may I return to work?
A: Most of our patients are able to return to work within 1 to 2 weeks, and nearly all activity can be resumed by 4 weeks. Men with jobs that require heavy lifting will need to be on light duties for 4-6 weeks.
Q: When will I know about the Pathology results?
A: Your surgeon will review the final pathology report with you at your first follow-up appointment which is typically 4-7 days after your surgery.
Q: When will my erections come back?
A: The return of erections depends on your age, your preoperative sexual performance status, your cancer and a good nerve sparing surgical procedure.Men are able to have return of sexual function starting from after a few days to upto 2 years after surgery. You will be extensively counselled and helped every step along the way by our experts even before surgery.
Q :When will I regain full urinary control ?
A : Most patients will have minimal dribbling of urination right after the catheter is removed, especially on performing strenuous activity. However, majority of patients regain complete urinary control within a few days to weeks. Performance of exercises to strengthen the pelvic floor muscles generally help in achieving early return to continence.
Prostate cancer is a very common disease. Studies of men without clinical evidence of prostate cancer and who died, often of accident or injury, have found that many men have prostate cancer and simply didn’t know it. Surprisingly, a man’s risk of prostate cancer being present somewhere in his prostate is approximately his age, minus 10, as a percent. As such, a 60 year old man has about a 50-50 chance of having some amount of prostate cancer within his prostate gland. On the other hand, for several decades, a man’s lifetime risk of dying of prostate cancer has been about 3-4%. As a result, it can easily be seen that most prostate cancers will never cause a problem during a man’s life. In general, it is felt that the cancers that are most likely to cause problems are those that are large and those which are aggressive in appearance when examined under a microscope.
Although ‘only’ 3% of men will die from prostate cancer, the actual number of men who die from the disease remains unacceptably high. For the past 3 decades, about 30,000 men each year have died from this cancer. As a result, physicians and the US government have sought to seek ways to reduce the number of men who die from the disease.
A major problem with prostate cancer is the fact that it almost never causes symptoms until it has spread; a man may have an early or even a very late prostate cancer and not know it until spread has occurred. Unfortunately, once spread of prostate cancer has occurred, although treatments are available that slow the cancer down, it is usually not curable.
As a result of this problem, since the turn of the 20th Century, physicians have recommended early detection as a way to find the cancer early, treat it, and prevent problems or death from the disease. Between the early 1900’s and about 1985, the only test that physicians had to detect prostate cancer was what is called the Digital Rectal Examination or DRE. This test is performed when a physician inserts a gloved finger into the patient’s rectum and feels the prostate, seeking any firm areas (called ‘nodules’) that might indicate the presence of cancer. This test, however, is imperfect. While some cancers can be found early in this fashion, Dr. Ian Thompson and colleagues in the early 1980’s found in a study of over 2,000 men that about two thirds of cancers found by this examination had already spread beyond the prostate. Clearly, a better test was needed.
The test the revolutionized prostate cancer detection was Prostate Specific Antigen or PSA. Although the protein that the test measures was first discovered in 1970, it wasn’t until the mid-1980’s that the potential for screening using this test was understood. The test measures PSA, a protein made by the prostate, in the blood. Early on, what level of the test that would be used to determine when the test was ‘abnormal’ was hotly debated. Some suggested a level of 2.5, others suggested a level as high as 10. Ultimately, the level that was selected was 4.0, measured in nanograms per milliliter or ng/mL.
In the late 1980’s, several large screening studies were published in the medical literature using PSA and a 4.0 ng/mL normal/abnormal cutoff. In these studies, men with a PSA level above 4.0 ng/mL were recommended to have a biopsy and men with a PSA below 4.0 ng/mL were told they were OK and no biopsy was performed.
Let’s pause just for a moment and discuss prostate biopsy. This procedure is about a 5-10 minute, office procedure. In general, prior to the procedure, the patient takes an antibiotic and refrains from taking any aspirin or other blood thinners for several days in advance. (You should check with your physician regarding the specific instructions that he or she uses.) Usually, the biopsy is performed with an ultrasound probe in the rectum. Using the ultrasound pictures as a guide, the physician first numbs the rectal wall and prostate using the same technique as a dentist uses, and then, again using the ultrasound pictures as a guide, an instrument with a needle that removes a small core of tissue from the prostate is employed. Usually, between 10-12 individual cores are removed. The potential risks of the procedure include bleeding and infection – stopping blood thinners prior to the biopsy and taking antibiotics reduces the risk of these complications.
Back now to screening in the 1980’s; after screening series were first reported, physicians began to learn more about PSA. The zone of 4 to 10 ng/mL generally was associated with about a 25% chance that prostate cancer would be found and levels about 10 ng/mL had rates above 50% for cancer detection. Although the higher the PSA level, the greater the likelihood that cancer would be found, the test was still treated as ‘normal’ (PSA less than 4) or ‘abnormal’ (PSA above 4). Screening recommendations began to proliferate; generally, if PSA was above 4 ng/mL or if the DRE examination was abnormal, a biopsy was recommended.
As screening began, several threads of discussion developed. These included:
Between about 1985 and 2004, the PSA test and prostate cancer screening really didn’t change very much. Some experts examined how lowering the cutoff level of PSA might change detection. They found, for example, that if a biopsy was performed for a PSA level between 2.5 and 4.0 ng/mL, between 20-25% of men were found to have prostate cancer. Some, as a result, recommended lowering the cutoff level of PSA to a value of 2.5 ng/mL. Others recommended using different PSA levels for men of different ages. For example, a lower PSA value was recommended to prompt a biopsy for a man between 50-60 years of age (to try to find prostate cancers earlier in these men with longer life expectancies) while using higher levels in older men who might have a lower risk from a slow-growing cancer.
What changed? In 2003, the results of the Prostate Cancer Prevention Trial were published. In this study (see prostate cancer prevention for a more detailed explanation), of the 18,882 men who enrolled, after 7 years of participation, all men, regardless of PSA level, were requested to have a prostate biopsy. The relationship between PSA and the risk of prostate cancer for all levels of PSA could now be understood. In 2004, Dr. Ian Thompson and colleagues published the initial examination of these results: among men with a PSA level between 0 and 4.0 ng/mL, 15% had prostate cancer. Even more concerning, of the cancers detected, 15% were aggressive tumors. This observation was extremely important as only about 8% of men in the US have a PSA value above 4.0ng/mL; the majority of men have values below 4.0 ng/mL.
This 2004 publication was the first insight into how prostate cancer screening might have ‘missed the mark’; if 15% of men with a PSA below 4 ng/mL have prostate cancer and if this is 92% of the US population have a PSA below 4 ng/mL, this means that there are far more prostate cancers in men with a PSA below 4 ng/mL than there are in men with higher PSA values.
Let’s again pause for a moment. Obviously, if prostate cancer can then exist at any level of PSA, should we stop doing PSA tests and just biopsy everyone? This question was on the lips of many physicians in 2004. Clearly, this was not a good approach. It took additional studies from the Prostate Cancer Prevention Trial and its 18,882 subjects to better understand how to use PSA. Let’s again pause for a moment. If we’re thinking about screening for heart disease and we have a blood test for cholesterol, how should we use it? If we use a cutoff level of cholesterol of 200 (as an example), let’s think about two individuals who walk into the physician’s office. One is a man who is obese, doesn’t exercise, has high blood pressure despite taking medications for it, has a family history of heart disease, smokes, and is 66 years old. This man’s cholesterol is 199. The other patient is a woman who is thin, runs marathons, is a nonsmoker, has a normal blood pressure, no family history of heart disease, and is 45 years old. This woman’s cholesterol is 201. Which of these two people has the greatest risk of heart disease right now? The answer is obvious – the man. Why? Because the other risk factors (smoking, weight, no exercise, family history, gender, age, etc) are all important in the risk of heart disease. (For the individual who is interested in this, you might want to look at the web site that helps to calculate this. It’s located at: http://hp2010.nhlbihin.net/atpiii/calculator.asp?usertype=prof)
Now, let’s go back to prostate cancer screening. Imagine two men: both have a normal prostate examination but one has a PSA of 3.9 ng/mL and the other has a PSA of 4.1 ng/mL. Who gets a biopsy? In the era before 2004-2006, it was only the man with a PSA of 4.1 ng/mL. The other man was told to come back next year. Let’s now assume that the man with a PSA of 3.9 ng/mL is 70, is African American, had a father with prostate cancer, and never had a biopsy before. On the other hand, the man whose PSA is 4.1 ng/mL is 55, is Caucasian, has no family history of prostate cancer, and had a biopsy last year that was negative.
So, how to work this out? The answer came again from the Prostate Cancer Prevention Trial.
In 2006, Dr. Thompson and a group of investigators led by a member of the UTHSCSA faculty, Dr. Donna Ankerst, examined how physicians could combine these known risk factors into a comprehensive, individualized estimate of risk of prostate cancer. This study resulted in the development of the Prostate Cancer Risk Calculator. (The calculator can be found at the Department of Urology web site at the UT Health Science Center here in San Antonio: http://deb.uthscsa.edu/URORiskCalc/Pages/uroriskcalc.jsp) The calculator allows a physician to determine the risk that prostate cancer would be found if a biopsy is performed and uses a combination of 6 risk factors in the calculation. The risk factors that are incorporated include:
An important aspect of the calculator is that it not only estimates the risk of prostate cancer but also estimates the risk of aggressive prostate cancer. (The term ‘aggressive’ means here a prostate cancer that grows and spreads more quickly and has a higher risk of causing death. The particular way that this is determined is by an examination of the cancer under the microscope. Specifically, it refers to Gleason 7, 8, 9, or 10 cancers.) Because many prostate cancers that are found at the time of biopsy are slow growing, it may be that the risk of finding an aggressive cancer may be more important to a patient and his physician than the risk of cancer overall.
This calculator revolutionized the way prostate cancer screening with PSA is conducted. At physicians offices across the world, the calculator can be found pre-loaded on office computers. At highly respected cancer centers and medical centers across the world, the calculator can be found on the PSA report itself. In addition to providing a highly-individualized report, it helped the prostate cancer community of researchers and practitioners understand some very important concepts. These include (and are based on medical publications that have resulted):
Obviously, this doesn’t make sense. (When we show this to our patients and teach this to other doctors, they immediately ‘get it’.) Ultimately, the patient himself, in association with the counsel of his physician, makes the decision whether to have a biopsy. However, given that the risk of cancer and of aggressive cancer is lower in the first man (with the abnormal DRE), after becoming fully informed about screening, he might just decide to have a repeat examination in 6-12 months.
Since the results of the PCPT became available as well as the analyses that were published afterwards including the prostate cancer risk calculator, prostate cancer screening has been completely changed. It’s also been made more complicated. Imagine the ‘old days’: “If your PSA is above 4.0 ng/mL or if your prostate examination (DRE) is abnormal, you should have a biopsy.” That recommendation, although simple for both the patient and physician, was, in retrospect, naïve and simply incorrect. It is now necessary to incorporate a group of risk factors into a discussion as to whether a biopsy is appropriate or not.
At the UT Health Science Center, for a man with a PSA result, we will routinely use the PCPT Prostate Cancer Risk Calculator to estimate his risk of both cancer and his risk of aggressive cancer. Before we do so, we explain to our patients that every man over the age of 55, regardless of his PSA, has a risk of prostate cancer. The three things we find to be important are his risk of cancer, his risk of aggressive cancer, and his concern about his cancer risk balanced against his concern about biopsy, potential diagnosis of cancer, and the risks of prostate cancer treatment.
Related to the first two risks, we often will begin by looking at a very low risk individual and calculating his risk of cancer and of aggressive cancer. An example might be a 55 year old Caucasian man with no family history of prostate cancer, a normal DRE, and a PSA of 0.5 ng/mL. His risk of cancer is 8.4% and his risk of aggressive cancer is 0.4%. Very few physicians or patients would recommend a biopsy in this man but it helps to understand that in his case, cancer may still be present; it’s just unlikely. It’s especially important to understand that in these low-risk men, the kind of cancer that may be present is often the slower-growing kind that often takes years or decades to develop or cause problems.
Another useful reference point for a patient (or a physician) who is not accustomed to using the risk calculator (and who oftentimes remembers the old days where the decision was so much easier: PSA above 4.0 ng/ml, you need a biopsy) is to recall that the rationale for recommending a biopsy for a PSA above 4.0 ng/mL was that there was a 25% risk of finding prostate cancer. Although we are not generally enthusiastic of using a single ‘cutpoint’ for a biopsy recommendation, it is helpful to compare the person’s risk with that 25% value.
We do feel that is very important to emphasize the aggressive prostate cancer risk estimate. Aggressive prostate cancers (Gleason scores of 7-10) constitute about a third of all prostate cancers but are the cause of two-thirds of the deaths from prostate cancer. These tumors tend to develop and spread much more quickly and, if a man or his physician’s emphasis is to find the tumor early and treat it successfully, it is these tumors for which early diagnosis may be more important. As a result, it could be that there are men for whom the aggressive cancer risk may be the deciding factor. For example, a man whose risk of cancer is 35% but whose risk of aggressive cancer is only 3% may decide not to have a biopsy while a man whose risk of cancer is 30% but whose risk of aggressive cancer is 15% might decide to have a biopsy.
Often left off from the discussion of prostate cancer screening is a discussion of what happens if prostate cancer is found. For most men who are screened with PSA and in whom a biopsy finds cancer, it will be found that the cancer is confined to the prostate. If the cancer is confined to the prostate, the national consensus is that a minimum of four treatment options should be offered to the patient: surgery (radical prostatectomy), radiation therapy with external beam, radiation therapy with implanted radioactive seeds, and active surveillance. (Other treatments are not excluded from this list; the list comprises the most commonly-used treatments in the US.) These treatments are explained in detail on our web site and also at other web sites including the American Cancer Society and American Urological Association web sites. None of these treatments has been proven to be dramatically superior to the other in high quality clinical trials. (Indeed, the only two treatments that have been compared head-to-head were surgery and surveillance. In this comparison, however, surveillance wasn’t in the form usually used in the US but was more of a hands-off followup with very little regard to treatment if the cancer began to spread. The study’s conclusions can be interpreted in two manners: on one hand, the risk of death from prostate cancer was significantly less with surgery than with surveillance; on the other, to prevent one death from prostate cancer, it was necessary for 20 men to undergo surgery.)
Experts in informed medical decision-making emphasize that prior to a decision to be screened or to have a prostate biopsy, that a man should understand not only the what if’s related to treatment but the potential side effects and complications from the treatments. For the two forms of radiation, the primary side effects include bowel irritation from the radiation (blood in the stool, more frequent bowel movements), urinary problems (including irritability of the bladder including urinary frequency, urgency, and bleeding as well as swelling of the prostate with difficulty emptying the bladder), as well as problems with sexual function (diminished quality or loss of erections). For surgery, the two primary risks include problems with sexual function (diminished quality or loss of erections) and urinary leakage. For patients who choose to watch their tumors and treat the tumor if there is a sign of growth (known as active surveillance), while there are no immediate problems, anxiety over the cancer diagnosis can be a problem. Additionally, the regular checkups, blood tests, and periodic prostate biopsies (to determine if the tumor is growing or becoming more aggressive) have their own risks (bleeding, infection) as well as can heighten the degree of anxiety, related in part to the potential risk of cancer growth and spread while the tumor is being watched.
Metformin is widely used anti-diabetic medicine. It can also act as an anti-cancer agent by activation of AMP-activated protein kinase (AMPK) pathway and subsequent inhibition of mTOR that blocks the cancer cell growth and proliferation. It may also lessen the symptoms of metabolic syndrome caused by androgen deprivation therapy. In this Phase II study patients with advanced prostate cancer will be randomly selected to receive castration only or castration plus metformin as first line treatment.
For veterans only; Patients will take Nexrutine® (an oral dietary supplement) prior to and during radiation treatment for prostate cancer or prior to surgery for prostate cancer. The purpose of the study is to see whether taking Nexrutine® will cause the PSA (Prostate Specific Antigen) to decline.
These references may be helpful for individuals who would like to read more about individualized decision-making in early detection of prostate cancer.
Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL, Minasian LM, Ford LG, Lippman SM, Crawford ED, Crowley JJ, Coltman CA Jr. Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. N Engl J Med. 2004 May 27;350(22):2239-46.
This is the landmark study that showed that there is a risk of prostate cancer for men with a PSA less than 4.0 ng/mL and that PSA shouldn’t be thought of as ‘normal’ or ‘abnormal’ but as related to the risk of prostate cancer: the higher the PSA, the higher the risk.
Thompson IM, Ankerst DP, Chi C, Goodman PJ, Tangen CM, Lucia MS, Feng Z, Parnes HL, Coltman CA Jr. Assessing prostate cancer risk: results from the Prostate Cancer Prevention Trial. J Natl Cancer Inst. 2006 Apr 19;98(8):529-34.
This is the study that developed the Prostate Cancer Risk Calculator using over 5,000 men from the Prostate Cancer Prevention Trial. The calculator uses age, PSA, rectal examination findings, race/ethnicity, family history, and prostate biopsy history to determine the risk of cancer and the risk of high grade cancer if a biopsy is performed.
Parekh DJ, Ankerst DP, Troyer D, Srivastava S, Thompson IM. Biomarkers for prostate cancer detection. J Urol. 2007 Dec;178(6):2252-9.
This is a nice review by Dr. Parekh of the UT Health Science Center faculty of the most promising new tests for prostate cancer detection today. The SABOR program at the Health Science Center is one of the National Cancer Institute’s cutting edge discovery programs.
Reed A, Ankerst DP, Pollock BH, Thompson IM, Parekh DJ. Current age and race adjusted prostate specific antigen threshold values delay diagnosis of high grade prostate cancer. J Urol. 2007 Nov;178(5):1929-32;
This study was the first to identify problems in the use of PSA when the physician uses different levels of PSA for different ages. These ‘age adjusted’ values may actually increase the likelihood of diagnosis of unimportant small tumors in young men while missing potentially lethal tumors in older men.