Prostate cancer is one of the most researched diseases and yet in remains one of the most controversial in regards to diagnosis, prognosis and treatment. In the following paper we will explore what is know about each of these areas. As we do it, these will become apparent that the guide lines concerning the approaches to prostate cancer are less scientific than most doctors are willing to admit. At the same time, it is essential that patients have a clear understanding of these controversies since they need to make decisions that may have consequences that affect both the quality and the length of their lives.
The one thing that no disagreement about is that prostate cancer is a major health concern and can be devastating to those who are afflicted with it. It is estimated that 200,000 men are diagnosed with prostate cancer every year and that about 38,000 can be expected to die of the disease. While these are alarming numbers by any standard looking at the full picture will offer some additional perspective.
During his lifetime, a man of age 80 has a 70% chance of having prostate cancer and a man of 50 has a 42% chance of harboring cancer in the prostate gland. This information is derived from autopsy reports and reveals that the incidence of hystological prostate cancer is much higher than the number diagnosed with clinical disease while alive. This means that most prostate cancers will never be clinically evident or life threatening.
Although the exact cause of prostate cancer is not known, it seems that most has a strong environmental component. One of the promoting factors of prostate cancer is testosterone. Testosterone seems to be an essential element in the promotion of prostate cancer since men who are castrated or have pituitary gland deficiencies are not known to develop prostate cancer. One argument against the role of testosterone in prostate cancer is that the disease is rarely found in younger men who have high levels of testosterone as compared to older men in whom the disease is most common. It thus seems that it is the total life times exposure to testosterone and not necessarily the absolute level at any one in a man’s life that is the critical factor.
The difference in the incidence of clinically relevant prostate cancer in different populations also speaks to an environmental cause of prostate cancer (very few cases are thought to have a genetic basis). For example, even though the incidence of clinically evident prostate cancer is much lower in Japan than it is in the United States, the percentage of prostate cancers found on autopsy is the same in both countries. When Japanese families migrate to the United States, the 1st and 2nd generations are found to have the same amount of clinically evident prostate cancer as the endogenous population. This suggest that it is not the presence of cancerous cells in the prostate gland that is of primary importance but rather environmental factors that stimulate these cells that is critical in the evolution of potentially lethal prostate cancer.
Some of the environmental factors that influence the progression of prostate cancer from the latent to the life threatening variety have been identified. A causal relationship has been demonstrated between prostate cancer and alcohol. An analysis of a double blind placebo controlled trial demonstrated that selenium may reduce both the development and mortality of prostate cancer. Another study indicated that vitamin E may have a positive affect in reducing the incidence of prostate cancer. This study showed that men who took 50IU of vitamin E/day had 32% fewer diagnosis of prostate cancer and 42% fewer deaths from prostate cancer compared to men who did not take vitamin E.
The study was highly significant containing almost 30,000 people. It is important to note that all subjects in the study were smokers but the results are likely to be applicable for non-smokers as well. It is also note worthy that the dose of vitamin E used was 3 times greater than the RDA (the dose that the government recommends.) Other vitamins, minerals and dietary factors have also been implicated in the prevention of prostate cancer. In summary it seems that the existence of cancer in the prostate gland is very common and that its presence does not mean the cancer will spread or become clinically significant in any way. In order for prostate cancer to grow, there must be factors in the diet or environment that promote growth of the cancerous cells.
Since prostate cancer is so common in the general population, the question of screening is very important. Currently the recommended modes for screening include digital examination of the prostate (DRE) and measurement of prostatic pacific antigen (PSA) in the blood. Although many more cases are being diagnosed because of advances in detecting PSA levels, studies have not demonstrated that screening and early detection of prostate cancer results in reduced deaths from the disease. The PSA has become a very popular screening test and because of it, we are diagnosing many more cases of prostate cancer than before the test was available.
The general assumption of using the test is that if we can detect the cancer at an early stage, it would be more curable. It is true that some statistics show that people are living longer today than they were before PSA testing became widely available but this is not because of prostatectomies. In fact, a study done in Sweden showed that long term survival increased after the wide spread use of PSA testing in spite of the fact that watchful waiting or palliative hormonal therapy were the most common treatments both before and after the advent of PSA testing. What this most likely indicates is that many of the prostate cancers being diagnosed with PSA would have never developed and become life threatening in the first place.
Once prostate cancer is diagnosed, the decision on what to do about it can be daunting. The dilemma arises in the fact that it is very difficult to predict which cancers will be progressive and life threatening which will remain dormant and never presented a problem to the patient. Several methods have been used in an attempt to determine which cases are most likely to be progressive. The Gleason scale is one tool used to estimate how aggressive a cancer may be. Studies show that the less differentiated a cancer is the more aggressive its behavior. A Gleason score is assigned by assigning a number of 1-5 to each of two biopsy samples that are most prevalently involved with cancer. A score of one is given if the cancer is well differentiated and a score of 5 is given to the least differentiated cancer cells. Thus, the lowest Gleasons score would be 2 having the least aggressive pathology and the highest score would be 10 having the most aggressive. Even with these guidelines in predicting the behavior of prostate cancer, the benefit of treating or even diagnosing a particular cancer can not be proven at this time.
With all this uncertainty, the decision on whether to treat a patient diagnosed with prostate cancer can be a very difficult one. The level of evidence in effectiveness of treating prostate cancer varies with the extent of disease at the time of diagnosis. It is generally assumed that when the cancer is discovered at an early stage (stage T1-T2) when the cancer has not penetrated the prostatic capsule, the situation is most treatable with cure as the goal. The treatment of choice is most often the prostatectomy (removal of the prostate gland). Not all studies however, demonstrated a clear advantage in the treatment of early stage prostate cancer. One study showed that at 10 years, survival of men diagnosed with prostate cancer who were only given palliative treatment at the time symptoms developed, lived as long as men of similar age in the general population.Another study also showed that watchful waiting (observation with no treatment), prostatectomy, or radiation all gave similar survival times. It would seem that the early treatment of prostate cancer with surgery or radiation has not been demonstrated to increase the life expectancy of the men who choose this treatment.
Is there better evidence to the effectiveness of treatments with more advanced disease? If surgery and radiation has not been shown to be effective in treating early stage prostate cancer it will not be effective when treating later stage disease.
The current recommendations are that immediate treatment is indicated since its results in better overall survival and fewer complications from prostate cancer. The evidence to support this position comes from a 1997 article in the British Journal of Urology. The actual results although statistically significant show only minimal increase in overall survival. The group that received treatment had a 7% more people alive at the end of the study. Of 467 people in the deferred group 328 were living compared to361 of 467 in the immediate treatment group. Not a dramatic difference at all. The results were even less clear for the subgroup that had no distant metastasis.
If the potential for surgery, radiation and hormonal treatment to increase survival is not impressive we would at least hope that the side effects from these treatments would be minimal and not negatively affect quality of life. Unfortunately, this is not the case.
Any surgery poses a risk. The risk of removing the prostate range from death to urinary incontinence and impotence. A national review of 10,600 cases demonstrates that the death rate from surgery is 2% and damage to the heart is 8%. In addition, 6% of men will require the use of urinary pads because of incontinence and a higher percentage will have urinary dribbling. As many as 60% of men may be impotent after surgery. And this is with the so-called nerve sparing surgery. These statistics are conservative compared to the results of a survey on Medicare patients who underwent prostatectomy. In this study, it was found that over 30% of men required urinary pads and 63% reported some problem with urinary incontinence. A 60% reported impotence and 90% of those who could have erections report that they were not sufficient for vaginal intercourse. In addition, the difference between the nerve-sparing surgery, which is suppose to have less side effects and standard surgery has not been demonstrated to decrease side effects. Fecal incontinence is another complication and outcome is affected by surgical method. Paradoxically there was more fecal incontinence in the nerve sparing surgery at 32% as compared to standard surgery at 17%.
Although the acute side effects of radiation are less severe than with surgery, over time radiation can pose serious long-term side effects. During radiation, patients may experience irritation of the bladder and rectum. In general, these symptoms tend to resolve over time but they may on occasion be severe enough to warrant surgery and may also become chronic. During and immediately after radiation potency is not affected but may become diminished over time. About 7% of men who received radiation report that they had urinary incontinence severe enough that they needed pads as compared to 30% who had surgery. Impotency was reported in 77% of men who received radiation as compared to 89% of men who had surgery. Radiation was however more likely result in frequent bowl movements at 10% as compared to 3% for those who had surgery.
The side effects of hormonal therapy are secondary to a reduced effect of testosterone on the physiology. Typical side effects include impotence, hot flashes and loss of sex drive. Diarrhea, nausea and liver toxicity have also been reported.
At this time it would seem that there is little justification to for the use of invasive and toxic methods for the treatment of prostate cancer. There is great discrepancy in the way prostate cancer is addressed in different parts of the country and even in different institutions in the same cities. These regional and institutional differences suggest that there is not strong evidence for the superiority of any one of the major modalities including surgery, radiation or watchful waiting.
Since physicians are not always forthcoming with the fact that there is scanty evidence to advocate the use of surgery and radiation in early prostate cancer and only slightly better evidence in relation to radiation and hormonal treatments in advanced prostate cancer, it is imperative that patients educate themselves on these issues and ask their physicians to justify the use of these invasive/toxic therapies with firm scientific evidence.
Does the lack of efficacy in standard treatment mean that if a person is diagnosed with prostate cancer they should do absolutely nothing? I believe the answer to this question is clearly no. There are non-toxic options that may affect the biological variables in such a way that outcome is positively effective. In my practice, I have treated several patients who had prostate cancers and were not treated by any conventional method. These patients responded with dramatic drops in PSA as well as improvement in symptoms. A look at the case history section on my web page will illustrate this point. While the case reports presented do not prove that it was the protocol that affected the positive outcomes, it is strongly suggestive. Until we have better proven methods to address this condition it seems that we should at least follow the principal of "first do no harm".
If you have prostate cancer please review the information in this article with your physician before making any treatment decisions.
Scardino: Early Detection of prostate Cancer. Hum Path 23:211-222,1992
Ballentine: Clinical evidence for and implications of the multistep development of prostate cancer. J Urol 143:742-746, 1990
Hayes: Alcohol use and prostate cancer risk in US blacks and whites. American J of Epid 143(7): 692-697, 1996
Colditz: Selenium and cancer prevention: promising results indicate further trials required. JAMA 276(24) : 1984-1985, 1996
Heinonen: Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J. NCI 90: 440-446, 1998
Eichholzer: Prediction of male cancer mortality by plasma levels of interacting vitamins: 17- year follow- up of the prospective Basel study. Inter. J. of Cancer 66(2): 145-150, 1996
Gann: Prospective study of plasma fatty acids and risk of prostate cancer. J Nat. Can. Inst. 86(4):281-286, 1994
Morton: The preventive role of diet in prostatic disease. Br. J Urol. 77(4): 481-493, 1996
Freidman: Case- control study of screening for prostetic cancer by digital rectal examination. Lancet 337(8756): 1526-1529, 1991
Chodak: Early detection of prostate cancer by routine screening. JAMA 252(23): 3261-3264, 1984
Brawer: Screening for prostatic carcinoma with prostate specific antigen. J. Urol. 147:841-845, 1992
Helgesen: Trends in prostate cancer survival in Sweden, 1960 through 1988: evidence of increasing diagnosis of nonlethal tumors. J Nat. Can. Inst. 88(17): 1216-1221, 1996
Resnick: Background for screening – epidemiology and cost effectiveness. Progr. Clin. Bio. Res. 269: 11-120, 1988
Beck: A critique of the decision analysis for clinically localized prostate cancer. J Urol 152(5, part 2): 1894-1899, 1994
Chodak: Results of conservative management of clinically localized prostate cancer. NJM 330(4): 242-248, 1994
Epstein: Prognosis of untreated stage A1 prostatic carcinoma: a study of 94 cases with extended follow up. J Urol. 136(4): 837-839, 1986
Medical Research Council Prostate Cancer Working Party Investigators Group: Immediate versus deferred treatment for advanced prostate cancer: initial results of the Medical Research Council Trial. Br J Urol. 79(2): 235-246, 1997.
Lu-Yao: an assesment of radical prostatectomy: time trends geographic variation, and outcomes. JAMA 269(20) 2633-2636, 1993.
Catalona: Return of erections and urinary continence following nerve sparing radical retropubic prostatectomy. J Urol. 150(3): 905-907, 1993
Fowler: Patient reported complications and follow up treatment after radical prostatectomy- the National Medicare experience: 1988-1990(updated June 1993). Urol. 42(6): 622-629, 1993.
Litwin: Quality of life outcomes in men treated for localized prostate cancer. JAMA 273(2): 129-135, 1995.
Bishoff: Incidence of fecal and urinary incontinence following radical perineal and retropubic prostectomy in a national population. J Urol. 160(2): 454-458, 1998.
Lim: Quality of life: radical prostatectomy versus radiation therapy for prostate cancer. J Urol. 154(4): 1420-1425, 1995.
Schellhammer: Pelvic complications after interstitial and external beam irradiation of urologic and gynecologic malignancy. World of Surgery 10(2): 259-268, 1986.
Fowler: Outcomes of external beam radiation therapy for prostate cancer: a study of Medicare beneficiaries in three Surveillance, Epidemiology, and End Results areas. J Clin Onc. 14(8): 2258-2265, 1996.
Kirschenbaum: Management of hormonal treatment effects. Cancer 75(7, Suppl): 1983-1986, 1995.
Wysowski: Fatl and nonfatal hepatotoxicity associated with flutamide. Annl. Int. Med. 118(11): 860-864, 1993.