Adjuvant and salvage radiotherapy following radical prostatectomy

Abstract

To identify the disease and treatment characteristics associated with outcome in patients undergoing adjuvant or salvage radiotherapy (RT) after radical prostatectomy (RP). This is a retrospective review of 237 men who were treated with definitive adjuvant or salvage radiotherapy at Duke University Medical Center and the Durham VA Medical Center between 1990 and 2002, following RP. Adjuvant RT was defined by a PSA ≤ 0.1 immediately prior to the initiation of RT. Progression-free survival (PFS) was calculated from the date of completion of RT to either the date midway between the PSA nadir and the first of three successive rises in PSA or the date of the detection of locally advanced or metastatic disease (whichever occurred first.) Patients who never exhibited a PSA decrease following RT were considered to have failed at time zero. PFS and overall survival (OS) curves were generated by the Kaplan-Meier method. The association of patient/tumor characteristics (age, pathologic T stage, surgical margin, seminal vesicle invasion, extracapsular extension, Gleason score and pre-operative and pre-RT PSA) and treatment factors (interval between RP and RT, radiation dose, adjuvant vs. salvage RT, and 2D vs. 3D planning) with outcome was determined by univariate and multivariate Cox proportional-hazards analyses. The median age for the entire group was 64 years with a median pre-operative PSA 10.7 ng/ml (range 1.5–200 ng/ml), median Gleason Score 7 (3–6 33%, 7 44%, 8–10 21%, unknown 2%) and median pathologic T stage of T3 (T1/T2 16%, T3 79%, T4 1%, TX 3%). At surgery, surgical margins were positive in 78%, seminal vesicle invasion present in 31% and extracapsular extension positive in 58% of patients. The median interval from surgery to RT was 11.5 months. 57% of the patients were treated using 2D technique and the remaining 43% received 3D conformal RT. All patients were treated with a 4-field box technique with a median dose of 6600 cGy (range 5490–7000 cGy.) Thirty-six patients (15%) underwent adjuvant RT and 182 patients (77%) received salvage RT; in 19 patients (8%) no post-operative/pre-RT PSA was available. Forty-nine patients received hormonal therapy prior to failure (10 in the adjuvant and 39 in the salvage RT group) and these patients were excluded from the outcome analyses. Median follow-up was 3.6 years. At the time of analysis, 62% of men were alive without evidence of disease, 27% were alive with disease, 3% were dead without evidence of disease and 7% were dead with disease. Of the 76 post-RT failures, the first sign of failure was rising PSA in 62, distant metastases in 12 and local recurrence in 2 patients. For all patients considered together, 5-year PFS and OS were 57 and 88 % respectively. For the adjuvant vs. salvage groups, 5-year PFS were 58 vs. 52%, respectively (p = 0.036). 5-yr OS did not differ significantly between the adjuvant and salvage RT groups (92 vs.86%, p = 0.47). On univariate analysis, pathologic T stage (Hazard ratio [HR] = 3.36, p = 0.002), salvage vs. adjuvant RT (HR = 2.95, p = 0.036), 3D vs. 2D planning (HR = 0.55, p = 0.035), extracapsular extension (HR = 1.86, p = 0.018), Gleason score (HR = 1.24, p = 0.017) and seminal vesicle invasion (HR = 1.61, p = 0.044) were significant factors associated with PFS. When the pathologic T stage was included in the multivariate analysis of PFS, no other factor attained statistical significance. This is the largest single-institution analysis to date of post-prostatectomy radiotherapy. The majority of patients treated with either adjuvant or salvage RT following RP were free from progression at 5 years after RT. No factor in addition to pathologic T stage was significantly associated with improved PFS on multivariate analysis. However, there is a suggestion of an advantage in PFS for early adjuvant treatment vs. delayed salvage therapy and for 3D vs. 2D planning