External-beam radiation therapy (EBRT)

In the Radiation Therapy Oncology Group (RTOG) trial RTOG-7706, prophylactic radiation therapy to clinically or pathologically uninvolved pelvic lymph nodes did not appear to improve OS or prostate cancer-specific survival.[29][Level of evidence A1]

The phase III randomized RTOG-9413 trial (NCT00769548) included 1,323 men with localized prostate cancer, an elevated PSA, and an estimated risk of lymph node involvement of 15%. Patients were randomly assigned to one of four treatment arms: whole-pelvic radiation therapy plus neoadjuvant and concurrent hormonal therapy; prostate-only radiation therapy plus neoadjuvant and concurrent hormonal therapy; whole-pelvic radiation therapy plus adjuvant hormonal therapy; or pelvic-only radiation therapy plus adjuvant hormonal therapy.[30]; [31][Level of evidence B1]

The phase III randomized RTOG-9413 trial (NCT00769548) included 1,323 men with localized prostate cancer, an elevated PSA, and an estimated risk of lymph node involvement of 15%. Patients were randomly assigned to one of four treatment arms: whole-pelvic radiation therapy plus neoadjuvant and concurrent hormonal therapy; prostate-only radiation therapy plus neoadjuvant and concurrent hormonal therapy; whole-pelvic radiation therapy plus adjuvant hormonal therapy; or pelvic-only radiation therapy plus adjuvant hormonal therapy.[30]; [31][Level of evidence B1]

Although RTOG-9413 showed increased PFS at 4 years for patients who had a 15% estimated risk of lymph node involvement and received whole-pelvic radiation therapy compared with prostate-only radiation therapy, OS and PSA failure rates were not significantly different.

In a randomized trial, 875 men with locally advanced nonmetastatic prostate cancer (T1b–T2 moderately or poorly differentiated tumors; T3 tumors of any grade) were randomly assigned to receive 3 months of a luteinizing hormone-releasing hormone agonist plus long-term flutamide (250 mg PO tid) with or without EBRT.[28][Level of evidence A1]

In a randomized trial, 875 men with locally advanced nonmetastatic prostate cancer (T1b–T2 moderately or poorly differentiated tumors; T3 tumors of any grade) were randomly assigned to receive 3 months of a luteinizing hormone-releasing hormone agonist plus long-term flutamide (250 mg PO tid) with or without EBRT.[28][Level of evidence A1]

Nineteen percent of the men had tumor stage T2, and 78% of the men had T3. At 10 years, both overall mortality (29.6% vs. 39.4%; 95% CI for the difference, 0.8%–18.8%) and the prostate–cancer-specific mortality (11.9% vs. 23.9%; 95% CI for the difference, 4.9%–19.1%) favored combined hormonal and radiation therapy.

In a randomized trial, 875 men with locally advanced nonmetastatic prostate cancer (T1b–T2 moderately or poorly differentiated tumors; T3 tumors of any grade) were randomly assigned to receive 3 months of a luteinizing hormone-releasing hormone agonist plus long-term flutamide (250 mg PO tid) with or without EBRT.[28][Level of evidence A1]

Although flutamide might not be considered a standard hormonal monotherapy in the setting of T2 or T3 tumors, radiation therapy provided a disease-free survival or tumor-specific survival advantage even though this monotherapy was applied. This analysis rests on the assumption that flutamide does not shorten life expectancy and cancer-specific survival. Radiation therapy was not delivered by current standards of dose and technique.