Adjuvant Radiotherapy For Pathologically Advanced Prostate Cancer: A Randomized Clinical Trial

UroToday.com - Despite the number of radical prostatectomies performed around the world, the role of adjuvant radiotherapy in the management of patients with locally advanced prostate cancer remains controversial.

In the November 15th issue of JAMA, Thompson and colleagues report the results of a prospective randomized trial designed to determine the role of radiation therapy in patients with pathologically advanced prostate cancer after radical prostatectomy.

This multi-institutional study enrolled 425 patients with pathologic stage T3N0M0 prostate cancer treated with radical prostatectomy between August 1988 and January 1997. Patients were randomized to radiation (60-64 Gy external beam) or observation arms. The primary endpoint was metastasis-free survival with PSA recurrence as the main secondary endpoint.

After a median follow-up of approximately 10 years, patients in the radiation arm exhibited a lower likelihood of PSA recurrence, with a median survival with freedom from PSA relapse of 10.3 years compared with 3.1 years in the observation arm (Hazard ratio 0.43, 95% CI 0.31 to 0.58). Similarly, radiation resulted in an improvement in overall recurrence-free survival, measured at 13.8 years for the radiation arm and 9.9 years for the observation arm ( p = 0.001).

There was a trend for radiated patients to exhibit improved metastasis-free survival, with 35.5% of men in the radiation arm developing metastasis or dying from prostate cancer, compared with 43.1% in the observation arm (p = 0.06). There was also a trend for patients in the radiation arm to demonstrate improved overall survival (median 14.7 years) compared with the observation arm (13.8 years), but this was not statistically significant. Radiation therapy was associated with a higher incidence of adverse events, most commonly urethral strictures (17.8% vs. 9.5%) and incontinence (6.5% vs. 2.8%).

This landmark study performed in a randomized fashion convincingly shows that adjuvant radiotherapy improves time to progression in patients with locally advanced prostate cancer. Unfortunately, the study was not designed to answer the several important questions: Should all patients with T3 disease receive adjuvant radiotherapy or should we follow their PSA until it becomes detectable? Should patients with seminal vesicle invasion and negative margins be radiated at all?

Many experts would argue that radiating all patients would unnecessarily expose too many patients to complications which would significantly impact their quality of life. Many young patients would rather opt for observation in order to protect their potency, as long as radiotherapy is used early in the event of a PSA recurrence. Clearly, there is a pressing need for a randomized trial that compares adjuvant radiotherapy to salvage radiotherapy at the time of a detectable PSA (0.1 to 0.4 ng/ml).

Ian M. Thompson Jr; Catherine M. Tangen; Jorge Paradelo; M. Scott Lucia; Gary Miller; Dean Troyer; Edward Messing; Jeffrey Forman; Joseph Chin; Gregory Swanson; Edith Canby-Hagino; E. David Crawford

JAMA.В 2006;296:2329-2335.
Reviewed by UroToday.com Contributing Editor Ricardo F. SГЎnchez-Ortiz, MD

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