LBA18 IMPACT OF TRANSIENT ANDROGEN DEPRIVATION THERAPY (ADT) WITH LEUPRORELIN LP 11.25 MG ON THE HISTOLOGICAL PROGRESSION OF INDOLENT PROSTATE CANCER (PC)–RESULTS OF A PHASE III TRIAL VERSUS ACTIVE SURVEILLANCE (AS)IMPACT OF TRANSIENT ANDROGEN DEPRIVATION THERAPY (ADT) WITH LEUPRORELIN LP 11.25 MG ON THE HISTOLOGICAL PROGRESSION OF INDOLENT PROSTATE CANCER (PC)–RESULTS OF A PHASE III TRIAL VERSUS ACTIVE SURVEILLANCE (AS)

Abstract

INTRODUCTION AND OBJECTIVES: Indolent forms of PC or low-risk prostate cancer (LRPC) represent 50% of newly diagnosed PC. Definition of LRPC and AS candidates remains problematic due to the lack of relevant markers of PC aggressiveness and difficulties in assessing disease progression under AS. Current knowledge suggests that PC aggressiveness could be assessed by response to early ADT. Long-term administration of a 5-alpha-reductase inhibitor may prevent the development of PC and reverse LRPC. Preliminary results of a pilot series at 2 French urology centers in LRPC pts receiving 2 drugs (analogs and 5-alpha-reductase inhibitor) for 3 months (mo), show tumor regression in about 60% of cases and suggest that LRPC can be reversed by ADT. Our study aims at confirming these results on a larger scale. METHOD(S): This was an open randomized phase III study comparing 2 treatment strategies. Arm A = AS after a single subcutaneous injection of Leuprorelin LP 11.25mg. Arm B = usual AS. Pts were eligible if they had a T1c or T2a PC, PSA inferior or equal to 10 ng/ml, Gleason score (GS) inferior or equal to 6 & staging Bx with 12 or more cores revealing the presence of positive cores & absence of core with tumor length > 3mm. The main endpoint was negative Bx at 12 mo. Pts were stratified according to age at diagnosis, PSA (total, density & nadir), testosterone, dynamic MRI staging, % of positive cores and length of tumor on the diagnosis biopsy. Secondary objectives were number of pts with GS equal or superior than 7, progression over time of disease clinical symptoms (IPSS score), tumor radiological progression by dynamic MRI, PSA progression, HAD Scale (anxiety) and International Index of Erectile Function (IIEF-5). RESULT(S): 115 eligible men from 22 sites were randomized in arm A (58 pts) & arm B (57 pts). The number of negative biopsies at 12 mo was statistically different (p=0.03) between arm A (28 (53%)) & arm B (17 (32%)). Among the secondary endpoints, the arm A strategy statistically improved outcome on: IPSS at 9 mo, PSA reduction at 3, 6 & 9 mo. Moreover, at 12 mo IIEF-5 score was not statistically different between the 2 arms. Other endpoints points were not significantly improved. No serious adverse events related to the study drug were observed. CONCLUSION(S): Results obtained with 3mo of Leuprorelin for LRPC suggest that ADT can be used to reverse LRPC lesions, hence improving the results obtained with subsequent AS. Early ADT led to a better quality of life at 9 months. This strategy also allows detecting hidden aggressive disease.