clinical study insights

The RTOG 9601 Experience: Amplifying the Clinical Benefit of Adjuvant Hormonal Therapy

by Neal Shore, MD, FACS

Overview

Clinical Study Title: 
Radiation With or Without Antiandrogen Therapy in Recurrent Prostate Cancer

Clinical Study Abstract:
NRG Oncology/RTOG 9601, a double-blind, placebo-controlled, randomized trial, was conducted from 1998 through 2003, with 760 patients post prostatectomy/lymphadenectomy for stage T2 or T3 disease who had recurred with prostate-specific antigen (PSA) levels of 0.2 to 4.0 ng/mL.

Patients underwent salvage radiation therapy and received either antiandrogen therapy (24 months of bicalutamide 150 mg daily or placebo during and after radiation therapy). Radiation therapy: photon energies of 6 to 10 MV to the original prostatic site, the tumor resection bed, and the membranous urethra; 2D and 3D planning systems were used according to institutional choice; regional pelvic lymph node treatment was omitted because all the patients had negative lymph node dissections; a total dose of 64.8 Gy was delivered in 36 daily fractions of 1.8 Gy at 5 sessions per week. The primary end point was the rate of overall survival (OS).

The median follow-up among the surviving patients was 13 years. The 12-year incidence of death from prostate cancer, as assessed by means of central review, was 5.8% in the bicalutamide group compared with 13.4% in the placebo group (P<0.001). The cumulative incidence of metastatic prostate cancer at 12 years was 14.5% in the bicalutamide group compared with 23.0% in the placebo group (P=0.005). The incidence of late adverse events associated with radiation therapy was similar in the 2 groups. Gynecomastia was recorded in 69.7% of the patients in the bicalutamide group compared with 10.9% of those in the placebo group (P<0.001).

 Reference:
Shipley WU, Seiferheld W, Lukka HR, et al. Radiation with or without antiandrogen therapy in recurrent prostate cancer. N Engl J Med. 2017;376(5):417-428.

Expert Commentary

Neal D. Shore, MD, FACS

Medical Director and CPI Carolina Urologic Research Center Managing Partner, Atlantic Urology Clinics
Myrtle Beach, SC

Shipley et al (N Engl J Med. 2017;376(5):417-428) and the NRG Oncology RTOG have completed a prospective, randomized, double-blind, placebo-controlled trial spanning nearly 2 decades, thus establishing the advantages of androgen receptor blockade for patients receiving moderate-dose pelvic radiation with high-dose bicalutamide. The investigators found a 23% higher likelihood of OS and a 51% lower likelihood of death in the bicalutamide treatment arm, findings that were both highly statistically significant. Of note, the number needed to treat (NNT) to demonstrate patient benefit exceeded the NNT that has been assessed for primary intervention with either radical prostatectomy or radiation therapy, thus further amplifying the clinical benefit of adjuvant hormonal therapy. By not reducing testosterone levels, expected side effect of bone demineralization and sexual dysfunction are lessened, albeit gynecomastia and associated breast symptoms were noted. Bicalutamide 150 mg is not an approved dosage within North America; nonetheless, the importance of this trial requires clinician consideration for adjuvant hormonal therapy to optimize the holy grail of personalized, patient decision-making in the setting of PSA relapse after radical prostatectomy, especially given the advancements in androgen receptor signaling inhibitors.

“The investigators found a 23% higher likelihood of OS and a 51% lower likelihood of death in the bicalutamide treatment arm, findings that were both highly statistically significant.”

Neal D. Shore, MD, FACS

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