AUA 2018: Impact of Transient ADT with Leuprorelin 11.25 Mg on the Histological Progression of Indolent Prostate Cancer–Results of a Phase III Trial vs Active Surveillance

San Francisco, CA ( Olivier Cussenot, MD, and colleagues presented results of their phase III trial randomizing men with indolent prostate cancer to Leuprorelin 11.25 mg vs active surveillance. Indolent forms of prostate cancer, or low-risk prostate cancer, represent 50% of newly diagnosed disease. The optimal definition of low-risk prostate cancer and active surveillance candidates remains problematic due to the lack of relevant markers of low-risk prostate cancer aggressiveness and difficulties in assessing disease progression under surveillance. 

Previous knowledge suggests that prostate cancer aggressiveness may be assessed by response to early ADT. Preliminary results of a pilot series at two French urology centers in low-risk prostate cancer patients gave 98 patients a single sub-cutaneous injection of 22.5 mg of leuprolide acetate with Atrigel 3-month depot associated with a daily oral intake of bicalutamide 50 mg/day during 15 days around the injection [1]. Among these men, 45 (45.9 %) had a negative biopsy after a median follow-up of 13 months [IQR 11-19.5]. Of the 53 patients with a positive biopsy, 17 had pathologic progression because of upgraded Gleason score (11 patients), four or more positive cores (three patients) or both (three patients). Based on these results, the authors proceeded to the current phase III trial.

This trial was an open randomized phase III study comparing two treatment strategies:

  • Arm A = active surveillance after a single subcutaneous injection of Leuprorelin LP 11.25mg
  • Arm B = standard of care active surveillance 
Patients were eligible if they had a T1c or T2a prostate cancer, PSA inferior or equal to 10ng/ml, Gleason score inferior or equal to 6 and staging biopsy with 12 or more cores revealing the presence of positive cores and absence of core with tumor length > 3mm. The primary endpoint of this trial was negative biopsy at 12 months. Secondary endpoints included (i) number of patients with Gleason score ≥7, (ii) progression over time of disease clinical symptoms (IPSS), (iii) tumor radiological progression via mpMRI, (iv) PSA progression, (v) IIEF-5, and (vi) HAD scale for anxiety.
This trial randomized 115 eligible men from 22 sites to arm A (n=58) and arm B (n=57). The number of negative biopsies at 12 months was lower for patients in arm A (n=28, 53%) and arm B (n=17, 32%) (p=0.03). Among the secondary endpoints, the arm A strategy improved: IPSS at 9 months, and PSA reduction at 3, 6, and 9 months (all p<0.001). Moreover, at 12 months IIEF-5 score was statistically better in arm A compared to arm B (p<0.001). Other endpoints points were not significantly improved; no serious adverse events related to the study drug were observed.
Cussenot concluded with several conclusions and take-home messages:

  • AS rates are increasing, upwards of 74% in Sweden in 2014 and ~40% in the US veteran population [2].
  • Results obtained with 3 months of Leuprorelin for low-risk prostate cancer suggest that ADT can be used to reverse low-risk prostate cancer lesions and improve results obtained with subsequent active surveillance.
  • Early ADT led to a better quality of life at 9 months
  • This strategy also allows detecting hidden, aggressive disease.

Presented by: Olivier Cussenot, MD, Institut Universitaire de Cancérologie, Sorbonne Université, Paris, France
Co-Authors: Raphaele Renard Penna, Eva Comperat, Paris, France, Abdel-Rahmène Azzouzi, Angers, France, Pierre Costa, Nimes, France, Stéphane Larre, Reims, France, Alain Ruffion, Pierre Bénite, France, Ludmila Fasla, La Défense, France, Dominque Delavierre, Orléans, France, Xavier Rebillard, Montpellier, France, Christian Pfister, Rouen, France, Jean-Philippe Fendler, Lyon, France, Jorgea Villamizar Vesga, Amiens, France, Frédéric Staerman, Reims, France


  1. Cussenot O, Cornu JN, Drouin SJ, et al. Secondary chemoprevention of localized prostate cancer by short-term androgen deprivation to select indolent tumors suitable for active surveillance: A prospective pilot phase II study. World J Urol 2014;32(2):545-550.
  2. Loeb S, Byrne N, Makarov DV, et al. Use of conservative management for low-risk prostate cancer in the Veterans Affairs Integrated Health Care System from 2005-2015. JAMA 15 May 2018 [Epub ahead of print].
Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA