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Treatments after Prostate Surgery

Although primary prostate surgery or radiotherapy is successful in many cases of prostate cancer, some patients will suffer a recurrence of the disease, which is most often first detected by a measurable PSA blood test.

This so-called biochemical recurrence affects 30% to 40% of patients after surgery. One risk factor for recurrence, the presence of cancer potentially outside the prostate after surgery, will affect about a third of men. Two studies in the March 2009 issue of The Journal of Urology report on clinical studies of treatment options.

Men who show increasing Prostate-Specific-Antigen (PSA) after surgery but without signs of metastases are offered a variety of options for treatment, including radiation, prostatectomy, observation or androgen deprivation therapy (ADT). Unfortunately virtually all patients treated with ADT progress to metastatic disease. Researchers investigated the addition of thalidomide to intermittent ADT in a double-blind, placebo-controlled multicenter study.

Intermittent ADT is increasingly being used in patients with biochemical recurrence since it has some advantages over continuous ADT. In this study, patients were first given ADT for 6 months, followed by thalidomide or placebo until their PSA increased (Oral Phase A) and the authors found that the median time to PSA increase was 15 months for the thalidomide patients versus 9.6 months for placebo. The next phase, Oral Phase B (OPB), was another 6 months of ADT followed by thalidomide and placebo, now switched between patient groups. During OPB, the median time to PSA increase was 17.1 months for thalidomide and 6.6 months for placebo.

Research conducted in 1994 found that thalidomide, an agent originally synthesized in 1954 and used as a sedative until it was linked to more than 10,000 severe malformations in infants, had antiangiogenic activity.

Writing in the article, William D. Figg, Medical Oncology Branch of the National Cancer Institute, National Institutes of Health, states, “Thalidomide is associated with an increase in PSA progression-free survival in men with biochemically recurrent prostate cancer after intermittent ADT. These effects were independent of any effects on testosterone. This is the first study to our knowledge to demonstrate the effects of thalidomide using intermittent hormonal therapy.”

Another multi-institution study, led by Ian M. Thompson, MD, University of Texas Health Science Center at San Antonio, demonstrates that adjuvant radiotherapy significantly improves survival after radical prostatectomy in patients with advanced prostate cancer. In this study initiated in 1988 of 425 men with aggressive prostate cancer, 211 were observed after surgery for signs of recurrence, and 214 received adjuvant radiotherapy shortly after surgery. Unlike most studies which have based results on PSA recurrence, this study’s endpoint was development of metastatic disease.

When data were most recently evaluated in 2008 after an average 12.7 year follow-up, radiation was found to significantly reduce the risk of metastases by 29% and significantly improved survival by 28%. In addition to the most important outcomes of prostate cancer (metastases and survival), the risk of a detectable PSA after surgery (the first evidence of disease recurrence) was reduced by 58% and delayed by more than 7 years. The authors found that all risk groups studied appeared to benefit.

Radiation therapy also significantly reduced the need for hormone therapy after surgery, a treatment which can have profound negative impacts on quality of life. Using measures of quality of life, the study found increases in patients’ urinary and bowel symptoms in the radiotherapy group at six weeks and two years, but these differences subsequently disappeared.

Dr. Thompson commented that “Adjuvant radiotherapy within 18 weeks after radical prostatectomy in a man with pT3N0M0 prostate cancer significantly reduces the risk of PSA recurrence, metastasis and the need for hormonal therapy, and significantly increases survival. All of the approximate 30,000 men each year that face this condition should be informed of the results of this study.”

Featured articles are “A Double Blind Randomized Crossover Study of Oral Thalidomide Versus Placebo in Patients With Androgen Dependent Prostate Cancer Treated With Intermittent Androgen Ablation” by William D. Figg, Maha H.Hussain, James L. Gulley, Philip M. Arlen, Jeanny B. Aragon-Ching, Daniel P. Petrylak, Celestina S. Higano, Seth M. Steinberg, Gurkamal S. Chatta, Howard Parnes, John J. Wright, Oliver Sartor and William L. Dahut, and “Adjuvant Radiotherapy for Pathological T3N0M0 Prostate Cancer Significantly Reduces Risk of Metastases and Improves Survival: Long-Term Followup of a Randomized Clinical Trial” by Ian M. Thompson, Catherine M. Tangen, Jorge Paradelo, M. Scott Lucia, Gary Miller, Dean Troyer, Edward Messing, Jeffrey Forman, Joseph Chin, Gregory Swanson, Edith Canby-Hagino and E. David Crawford.

Both appear in The Journal of Urology, Volume 181, Issue 3 (March 2009) published by Elsevier.

Linda Gruner | alfa
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