PD57-12: The impact of persistently elevated PSA levels on progression and survival of patients undergoing cytoreductive radical prostatectomy for oligometastatic prostate cancer

Elio Mazzone, Giorgio Gandaglia, David Pfister, Shahrokh Shariat, Bernhard Grubmüller, Nicola Fossati, Giuseppe Fallara, Antony Pellegrino, Daniele Robesti, Donato Cannoletta, Aldo Rizzo, Vito Cucchiara, Filippo Scalvi, Gabriele Sorce, Francesco Pellegrino, Andrea Gallina, Vincenzo Mirone, Pierre I Karakiewicz, Francesco Montorsi, Jeffrey Karnes, Alberto Briganti, Axel Heidenreich

Introduction: Cytoreductive radical prostatectomy (cRP) represents an option in oligo-metastatic prostate cancer (mPCa). However, the optimal multi-modal strategy of these men is unknown also considering the lack of markers of disease aggressiveness. We hypothesized that persistently elevated PSA levels after cRP might impact on outcomes and might guide post-operative treatments

Methods: We evaluated 152 men who received cRP plus extended pelvic lymph node dissection (ePLND) for oligo-mPCa at four referral centres. Of these, 90 (59%) men received neo-adjuvant treatment and were excluded. This resulted in 62 patients treated with cRP without neoadjuvant ADT. Patients were eligible for cRP if they had: (1) completely resectable PCa; (2) =5 osseous metastases; (3) no gross retroperitoneal nodal metastases; (4) no pelvic nodal metastases >3 cm; (5) no visceral metastases. PSA persistence after cRP was defined as =0.1 ng/ml at 6 weeks after cRP. Clinical recurrence (CR) was defined as additional metastases during follow-up. Kaplan-Maier analyses assessed time to CR and CSM overall and after stratification according to PSA persistence. Multivariable Cox regression models tested the impact of PSA at 6 weeks on CR and CSM after adjusting for grade group (=8 vs 9-10), stage (=pT3a vs =pT3b; pN0 vs pN1) and adjuvant ADT.

Results: Median follow-up for survivors was 43 months. Overall, 33 (53%), 29 (47%) and 37 (60%) patients had grade group 5, pT3b and pN1 disease. A total of 29 (47%) patients experienced PSA persistence and 44 (71%) patients received additional systemic therapies. Overall, 28 and 10 patients experienced CR and CSM at last follow-up. The 5-year CR- and CSM-free survival rates were 49 and 82%. The 5-year CR- and CSM-free survival rates were 26 vs. 74% and 67 vs 90% for men with vs. without PSA persistence (all P<0.05). At multivariable analyses, PSA level at 6 weeks after surgery represented a strong independent predictor of higher CR (Hazard ratio [HR]: 1.02) and CSM (HR: 1.05; p=0.01).

Conclusions: Surgery without neoadjuvant therapies achieved an initial biochemical response in roughly 50% of men receiving cRP. The first PSA value at 6 weeks after cRP represents an important predictor of CR and CSM in oligo-mPCa patients who did not receive previous neoadjuvant ADT. Patients with PSA persistence should be counselled about their unfavourable prognosis and exposed to more extensive multimodal treatments. Source of

Funding: none