Dose Escalated Radiation Therapy for High Risk Prostate Cancer: Outcomes in the Modern Era with Short Term Androgen Deprivation Therapy

Abstract

Randomized data support the use of long-term Androgen Deprivation Therapy (ADT) in combination with Radiation Therapy (RT) for men with high-risk prostate cancer. However, patients treated in those studies predominantly had locally advanced disease (T2c-T4) and were treated with lower doses of RT. This study reviewed the outcome of a contemporary cohort of intermediate and high risk men treated with RT and short-term ADT. The study cohort was identified from a clinical database including 707 patients with T1-3N0M0 adenocarcinoma of the prostate treated with primary external beam RT between 1992 and 2006. 184 men had any single risk factor of PSA ≥10, clinical stage ≥T2b, or Gleason score ≥7. Median RT dose was 74 Gy; 55% were treated with Intensity Modulated RT. The treatment volume typically included only the proximal seminal vesicles and prostate; 13 men (7%) were treated with whole pelvic RT. All patients received ADT of no more than 6 months (median 4 months), consisting of a gonadotropin releasing hormone analog. 122 men (68%) were also treated with an anti-androgen. Univariate and multivariable analysis were performed for risk factors including T-stage, Gleason score, RT dose, and PSA level. With a median follow-up of 51 months, the 4-year Freedom From Biochemical Failure (FFBF, nadir+2 definition) was 83% for all patients. The 4-y FFBF was significantly higher for patients with intermediate-risk disease compared to patients with high-risk disease (92% vs 73%, p = 0.0039). Clinical T3 disease was the only tested variable associated with FFBF on univariate (4-y FFBF 46% vs 87% for T1-2c disease, p = 0.0303) and multivariable analysis (HR 3.9, p = 0.0016). On subset analysis of high risk patients (NCCN criteria), clinical T3 disease (4-y FFBF 46% vs 80%, p = 0.0303) and RT dose <74 Gy (4-y FFBF 64% vs 80%) had poorer outcome on univariate analysis. These factors were not significant on multivariable analysis although there was a statistical trend for both (p = 0.0650 and p = 0.0597, respectively). Because the high-risk prostate cancer patient seen today differs significantly from the patients treated in the randomized trials supporting the use of long term ADT, the recommendation of long term ADT may not need to be a foregone conclusion. This study suggests that for the high-risk patient with clinically localized disease treated with ≥74 Gy, short term ADT is a reasonable consideration to help reduce the risks associated with long term therapy.