Does biochemical progression after radical prostatectomy and adjuvant radiotherapy for locally advanced prostate cancer invariably impact cancer-specific mortality?

Briganti, A.1, Suardi, N.1, Gallina, A.1, Scattoni, V.1, Abdollah, F.1, Capogrosso, P.1, Finocchio, N.1, Moschini, M.1, Di Muzio, N.2, Cozzarini, C.2

1Urological Research Institute, Vita Salute San Raffaele University, Dept. of Urology, Milan, Italy, 2Urological Research Institute, Vita Salute San Raffaele University, Dept. of Radiotherapy, Milan, Italy

Introduction & Objectives

Previous prospective, randomized trials have shown a significant impact of adjuvant radiation therapy (RT) on biochemical progression (BCR) in patients with locally advanced prostate cancer (PCa) at radical prostatectomy (RP). However, the prognosis of patients who experienced BCR after adjuvant RT has not been extensively investigated.

Material & Methods

The study included 227 consecutive patients treated with RP, pelvic lymph node dissection and adjuvant RT for locally advanced PCa (pT3a/pT3b) and/or positive surgical margins (SM+) between 1988 and 2006 at a single tertiary referral center. All patients had complete pathological data (including pathological stage and Gleason sum at RP, lymph node and surgical margin status). All patients experienced BCR (defined as two consecutive PSA values>0.2 ng/ml). Time to BCR and complete follow-up data were available for all patients. The Kaplan Meier method explored time to cancer-specific mortality. Univariable and multivariable Cox regression models tested the association between predictors (namely, pre-operative PSA, pathological Gleason sum and stage, time to BCR) and cancer specific mortality (CSM).

Results

Mean and median age at BCR were 65 and 65.3 yrs, respectively. Mean and median PSA at surgery were 26 and 14.7 ng/ml, respectively. RP Gleason sum was 2-6, 7 and 8-10 in 22.4, 37.9 and 39.7% of patients, respectively. Extracapsular extension and seminal vesicle invasion (SVI) were present in 51.8 and 48.2% of patients, respectively. Overall, 35.8% of patients had SM+. Kaplan Meier analysis, CSM-free survival rates at 5 and 10 years after BCR were 81 and 70%, respectively. At univariable Cox regression analyses, age, PSA, RP Gleason sum, SVI, LNI and time to BCR were significantly associated with higher rates of CSM. At multivariable analyses, after adjusting for age, PSA, SVI and RP Gleason sum, the presence of LNI (HR:23.7, p=0.01) and time to BCR (HR: 0.93, p=0.01) represented independent predictors of CSM. When patients were stratified according to the most informative cut-off for time to BCR (36 months), patients who experienced BCR < 36 months after RP had a 3.6 fold increased risk of CSS.

Conclusions

This is the first study focusing on the outcome of patients who failed after adjuvant RT for locally advanced prostate cancer and/or positive surgical margins. We demonstrated that not all patients experiencing BCR after RP and adjuvant RT have the same survival outcome. In case of failure after adjuvant RT, the presence of LNI at RP and a time to BCR < 3 years may represent selecting criteria for the identification of patients suitable for accrual in clinical trials.