The CancerWeb Report, What's New In Cancer: November, 1996
Prostate Cancer

• To screen or not to screen? - This was the question discussed in the News section of the September, 1996 issue of Annals of Oncology (Ann Oncol 7:648, 1996), a European cancer journal. It is also a question discussed in many prior issues of the CancerWeb Report. European physicians usually do not recommend general population screening for prostate cancer, in contrast to the US where the American Cancer Society recommends an annual PSA test for all men over 50. The surgical approach of prostatectomy frequently follows the finding of an elevated PSA and a positive biopsy. European reluctance to follow the same route stems in part from the perceived deficiencies of PSA, which does not always reflect the severity of the cancer. Also there is widespread concern that since most cases of prostate cancer disclosed by PSA are unlikely to progress significantly, surgery with its potential risks of incontinence, impotence and even mortality, may be worse for this large group of patients than no treatment at all. Cost is another factor. To complicate the issue, the alternative course of watchful waiting, even if there were clinical data to strongly support it, is difficult to follow in the highly litigious environment of the US. The problem is that there are no really adequate clinical data to strongly support any particular course of action. A major European study, coordinated by Drs. Denis and Schroeder at Erasmus University in Rotterdam, is underway to compare the outcome of screened populations versus those who did not undergo regular screening. Unfortunately, the results may not be known until the year 2008. A group at Harvard University, led by Dr. Kantoff, is studying a potential new test which might be better than PSA: the number of glutamines in the androgen receptor molecule. In preliminary work, a lower number seems to be more definitely connected to aggressive cancer than is an elevated PSA. The number also is lower among US blacks who have a higher incidence of and mortality from prostate cancer than whites. Even if it proves itself in more extensive trials, application of this test also may be several years away. (Editorial News Section, Ann Oncol 7:648, 1996)

  ---

• Combination of overexpression of bcl-2 and p53 best predicts lack of response to hormone therapy - Abnormal expression of the proto-oncogene bcl-2 (overexpression) and of the tumor suppressor p53 (usually accumulation of an abnormal form in the cell nucleus) may reveal a disorder of programmed cell death, since bcl-2 protects cells from this process while abnormal p53 cannot mediate it. A report by doctors from Newcastle upon Tyne in the UK, appearing in the October, 1996 issue of the British Journal of Cancer, examined the relationship between expression of bcl-2 and p53 and response to deprivation of androgen, brought about either by castration or by administration of a luteinizing hormone-releasing (LHRH) drug. Of 77 men with untreated prostate cancer, 45 had locally advanced and metastatic disease and were treated by hormone manipulation; 28 of these failed to respond or relapsed within 37 months. Among 77 cancers, 37 had overexpression of bcl-2 and 70% of these were hormone resistant, while 23 had nuclear p53 staining (reflecting accumulation of the protein) and 67% showed resistance to endocrine treatment. Of the patients with both bcl-2 overexpression and p53 accumulation, 81% did not respond to hormone manipulation. Combined detection of these two proteins may a useful predictor of response to androgen deprivation. (Apakama, Br J Cancer 74:1258, 1996)

  ---

• How low does PSA have to be brought down by radiotherapy to assure optimum results? - According to researchers at the Dekalb Medical Center in Atlanta, Georgia, radiotherapy should bring PSA down to undetectable levels, that is less than or equal to 0.5 ng/mL to assure optimum treatment of prostate cancer. Writing in the November, 1996 issue of the Journal of Clinical Oncology, they describe their results in 536 patients without positive lymph nodes, treated from 1984 to April, 1994, with implants of radiolabeled iodine (125I) in the prostate, followed by external beam radiation. Those with undetectable PSA had a 95% 5-year and an 84% 10-year disease-free survival, whereas the patients in whom the lowest level was 0.6-1.0 ng/mL had a 5-year survival of 29%, and all whose PSA never fell below 1.0 ng/mL failed to survive. (Critz, J Clin Oncol 14:2893, 1996)

  Editor's Comment: - Undetectable PSA is accepted as an appropriate finding 6 weeks after surgical prostatectomy, but there has been no consensus about levels after radiation treatment. In fact, as an accompanying editorial in the same journal issue (McLaughlin, J Clin Oncol 14:2889, 1996) makes evident, there is still no consensus, and perhaps there should not be. Disease may still recur after surgery even though PSA may have been undetectable, because of residual tumor cells in the body too small in number to make measurable amounts of the marker. Unlike surgery, radiation therapy leaves behind normal prostate tissue that can still make PSA. This touches on issues such as how rapidly PSA values rise after treatment, how best to include in the analysis data from patients who respond only slowly to treatment, and the time at which a PSA value has most prognostic significance. All these issue require clarification.