Anti-Androgen Therapy Boosts OS After Radiotherapy For Prostate Cancer Recurrence

Overall survival is longer in men with recurrent prostate cancer after prostatectomy if they receive bicalutamide plus salvage radiotherapy than radiation alone

medwireNews: By adding 2 years of bicalutamide therapy to salvage radiotherapy, long-term overall survival (OS) is increased and the risk of metastases reduced, indicates a long-term study of men with prostate cancer recurrence after prostatectomy.

“The higher rate of overall survival with antiandrogen therapy than with placebo became evident in the second decade after therapy”, say William Shipley, from Massachusetts General Hospital in Boston, USA, and co-investigators who explain that the slow nature of prostate cancer progression meant that a long-follow-up was necessary to show this benefit.

The trial included a median of 13 years of follow-up for 760 men who had undergone surgery with lymphadenectomy but had T2 or T3 disease without nodal involvement and a detectable prostate-specific antigen (PSA) level of 0.2–4.0 ng/mL.

The 12-year actuarial OS rate was 76.3% in the 384 men who were treated with 24 months of bicalutamide 150 mg/day alongside 64.8 Gy of radiotherapy in 36 daily fractions at a rate of five per week. This compared with an OS rate of 71.3% for the 376 men who were given placebo plus radiotherapy, giving a significant hazard ratio (HR) for death of 0.77.

The rate of prostate cancer-specific death at 12 years was also significantly lower in the patients given anti-androgen therapy, (5.8 vs 13.4%, HR=0.49), as were the 12-year cumulative incidences of metastatic prostate cancer (14.5 vs 23.0%, HR=0.63) and second episodes of biochemical recurrence (44.0 vs 67.9%, HR=0.48).

Multivariate analysis showed that poor OS in the trial participants was significantly predicted by receipt of placebo, an entry PSA level above 1.5 ng/mL, a pathology Gleason score of 8–10, a Karnofsky performance status score of 80 or 90, and age of or above 65 years.

Subgroup analyses suggest that patients with more aggressive prostate cancer, such as those with a baseline PSA of 1.5 ng/mL or higher, and those with a positive surgical margin may derive the most benefit from the addition of anti-androgen therapy, the authors observe in the New England Journal of Medicine.

The treatment groups did not differ with regard to early urinary, bowel or haematological adverse events. Late adverse events were also comparable, with late genitourinary grade 3 side effects reported in 7.0% of patients given bicalutamide and 6.0% of placebo-treated patients. Grade 4 events occurred in 0.3% and 0.8%, respectively.

Gynaecomastia occurred in 69.7% of patients given anti-androgen therapy, with grade 1, 2 and 3 events reported in 42.4%, 23.6% and 3.7%, respectively. This compared with 8.8%, 2.1% and 0.0% of controls.

Ian Thompson Jr, from Christus Santa Rosa Health System in San Antonio, Texas, USA, discusses the study’s “remarkable contribution” in a linked comment and notes that gynaecomastia “can be distressing but can be mitigated by prophylactic radiation of the breast or by the administration of tamoxifen.”

He summarises: “The number needed to treat with the nonsteroidal antiandrogen drug bicalutamide to prevent one death from prostate cancer was 20.

“By comparison, the number needed to treat (surgery or radiation therapy) to prevent one death from prostate cancer has been estimated to be 27, which shows the magnitude of the benefit of antiandrogen therapy.”


Shipley WU, Seiferheld W, Lukka HR, et al. Radiation with or without antiandrogen therapy in recurrent prostate cancer. N Engl J Med; 376: 417–428 2 February 2017. DOI: 10.1056/NEJMoa1607529

Thompson Jr IM. Improved therapy for PSA recurrence after prostatectomy. N Engl J Med; 376: 484–485 2 February 2017. DOI: 10.1056/NEJMe1614133  

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