Anti-androgen therapy improves survival for men with cancer recurrence after prostatectomy

Men with prostate cancer who have prostate-specific antigen recurrence following radical prostatectomy have improved survival with radiotherapy and a long-term course of anti androgen therapy.

It is well established that a rising serum prostate-specific antigen (PSA) level is an indication of cancer progression in men diagnosed with prostate cancer and treated with radical prostatectomy (RP). For these patients, adding 24 months of anti-androgen therapy (AAT) during and after salvage radiotherapy (RT) improves overall survival statistically compared with salvage RT alone, according to the long-term results of a clinical trial conducted by the Radiation Therapy Oncology Group (RTOG), now conducting research as NRG Oncology. The RTOG 9601 study results presented today at the plenary session of the 57th Annual Meeting of the American Society for Radiation Oncology (ASTRO) also reveal that the addition of ATT to salvage RT reduces prostate cancer death and the development of metastatic prostate cancer without increasing radiation toxicity.

Over the last 25 years, many men with intermediate-risk prostate cancer have undergone RP, yet many will face recurrence subsequently with a rising PSA,” says lead study author William U. Shipley, M.D., FACR, FASTRO, who is the Andres Soriano Distinguished Professor of Radiation Oncology at the Massachusetts General Hospital and the Harvard Medical School, both in Boston. “Our results show that salvage RT plus peripheral androgen blockade (AAT with bicalutamide), when compared with RT plus a placebo, improved long-term overall survival and reduced death from prostate cancer without adding significantly to radiation toxicity. Because prostate cancer progresses slowly, follow-up of over 12 years was necessary to demonstrate a statistically better patient survival with combined AAT and RT.

With a median follow-up now of 12.6 years, the study results showed the actuarial overall survival at 10 years was 82 percent for the RT plus AAT arm and 78 percent for the RT plus placebo arm (P = 0.036). The 12-year incidence of prostate cancer-related deaths was 2.3 percent for the RT plus AAT arm, compared with 7.5 percent for the RT plus placebo arm. At 12 years, the cancer had metastasized in 51 patients (14 percent) in the RT plus AAT arm, compared with in 83 patients (23 percent) in the RT plus placebo arm. Additionally, late bladder and bowel toxicity were low and similar in both groups, whereas 70 percent of men in the RT plus AAT arm reported swelling of the breasts, compared with 11 percent in the RT plus placebo arm.

Conducted at sites across the United States and Canada from 1998 to 2003, the RTOG 9601 trial enrolled 761 men with prostate cancer who had undergone RP and subsequently developed elevated PSA levels. The patients were randomized to receive either salvage RT plus placebo (377 patients) or salvage RT plus AAT (384 patients).

Further statistical analyses, which are underway, may identify subgroups of patients who may not benefit from hormone therapy added to salvage RT and other subgroups for whom it may be especially beneficial. Also, because anti-androgen therapy, which suppresses testosterone production, is now used more commonly than peripheral androgen blockade with AAT, its use should be evaluated,” says Shipley in regard to next research steps for the population of post-RP patients referred for salvage RT. Shipley also emphasizes the clinical researchers’ gratitude for the willingness of the patients to participate on this and other randomized trials and for the essential role they play in advancing cancer care.

The results of this trial are testament to the importance of phase III randomized controlled trials for determining significant benefits. Congratulations to the trial team for their commitment to obtaining the quality of research data necessary for impacting the clinical care of patients with prostate cancer,” says Walter J. Curran Jr., M.D., an NRG Oncology Group Chairman and Executive Director of the Winship Cancer Institute of Emory University in Atlanta.

57th Annual Meeting of the American Society for Radiation Oncology (ASTRO) 2015 San Antonio, Texas, USA

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Soy protein supplementation does not reduce risk of prostate cancer recurrence

Among men who had undergone radical prostatectomy, daily consumption of a beverage powder supplement containing soy protein isolate for 2 years did not reduce or delay development of biochemical recurrence of prostate cancer compared to men who received placebo, according to a study in the July 10 issue of JAMA.

“Prostate cancer is the most frequently diagnosed malignancy and the second most frequent cause of male cancer death in the United States and other Western countries but is far less frequent in Asian countries. Prostate cancer risk has been inversely associated with intake of soy and soy foods in observational studies, which may explain this geographic variation because soy consumption is low in the United States and high in Asian countries,” according to background information in the article.

“Although it has been repeatedly proposed that soy may prevent prostate cancer development, this hypothesis has not been tested in randomized studies with cancer as the end point. A substantive fraction (48 percent – 55 percent) of men diagnosed as having prostate cancer use dietary supplements including soy products, although the exact proportion is not known. However, no evidence exists that soy supplementation has any prostate cancer-related benefits for these men. Soy contains several constituents, including isoflavones, which possess anticancer activities in laboratory studies.”

Maarten C. Bosland, D.V.Sc., Ph.D., of the University of Illinois at Chicago, and colleagues examined whether daily consumption of a soy protein-based supplement would reduce the rate of recurrence or delayed recurrence of prostate cancer in men at high risk of recurrence after radical prostatectomy. The randomized trial was conducted from July 1997 to May 2010 at 7 U.S. centers and included 177 men. Supplement intervention was started within 4 months after surgery and continued daily for up to 2 years, with prostate-specific antigen (PSA) measurements made at 2-month intervals in the first year and every 3 months thereafter. Participants were randomized to receive a daily serving of a beverage powder containing 20 g of protein in the form of either soy protein isolate (n=87) or as placebo, calcium caseinate (n=90).

The trial was stopped early for lack of treatment effects at a planned interim analysis with 81 evaluable participants in the intervention group and 78 in the placebo group. Overall, 28.3 percent of participants developed biochemical recurrence (defined as development of a PSA level of ≥0.07 ng/mL) within 2 years of entering the trial. Twenty two (27.2 percent) of the participants in the intervention group developed confirmed biochemical recurrence, whereas 23 (29.5 percent) of the participants receiving placebo developed recurrence. “Among participants who developed recurrence, the median [midpoint] time to recurrence was somewhat shorter in the intervention group (31.5 weeks) than in the placebo group (44 weeks), but this difference was not statistically significant,” the authors write.

Adherence was greater than 90 percent. There were no differences in adverse events between the 2 groups.

“The findings of this study provide another example that associations in observational epidemiologic studies between purported preventive agents and clinical outcomes need confirmation in randomized clinical trials. Not only were these findings at variance with the epidemiologic evidence on soy consumption and prostate cancer risk, they were also not consistent with results from experiments with animal models of prostate carcinogenesis, which also suggest reduced risk,” the researchers write.

“One possible explanation for these discrepant results is that in both epidemiologic studies and animal experiments, soy exposure typically occurred for most or all of the life span of the study participants or animals; there are no reports of such studies in which soy exposure started later in life. Thus, it is conceivable that soy is protective against prostate cancer when consumption begins early in life but not later or when prostate cancer is already present. If this is the case, chemoprevention of prostate cancer with soy is unlikely to be effective if started later in life, given the high prevalence of undetected prostate cancer in middle-aged men.”

Bosland et al., (2013). Effect of soy protein isolate supplementation on biochemical recurrence of prostate cancer after radical prostatectomy. JAMA310:170-178 [Abstract]