Effectiveness and Distribution of Testosterone Levels within First Year of Androgen Deprivation Therapy in a Real-World Setting: Results from the Non-Interventional German Cohort LEAN Study - Beyond the Abstract

There is common agreement that real-world trials are expected to extend existing knowledge on the efficacy and tolerability of a given agent in the target cohort. As results obtained in phase 3 studies can actually only be applied to a highly selected and frequently younger patient cohort with limited comorbidity in these trials, real-world studies permit to investigate the role of a given therapy in daily practice. Furthermore, adequately designed real-world trials may also provide answers to important clinical questions that can only be examined in clinical routine.

The LEAN study (www.germanctr.de, trial ID: DRKS00005643, “Observation of Leuprone® HEXAL® in treatment practice. Non-interventional study on effectiveness and tolerability and on the influence of anamnestic factors”) is an open-label, multi-centre, non-interventional German cohort study of Leuprone HEXAL in patients with advanced prostate cancer.1

It is notable that patients included in this observational study tended to be approximately 1 decade older and had higher comorbidity if compared with patients included in contemporary phase 3 trials in hormone-naive prostate cancer. This difference is also reflected by the distribution of the ECOG status.

In general, toxicity was as expected, no new safety signals were registered and premature patient-triggered termination of therapy may serve as a reliable surrogate parameter. The observation that only 3.6% of patients chose to terminate ADT early suggests good tolerability of the leuprorelin implant in this older and frailer cohort.

Regarding efficacy, the overall results on testosterone suppression were in line with the results reported in the prospective randomized PR-7 trial, which serves as the reference for the castrate level of <0.5 ng/mL recommended by the National Comprehensive Cancer Network (NCCN) and the German S3 guideline.2,3 In these days of competition for the lowest testosterone levels it is important to highlight that, like in PR-7, also in the LEAN study testosterone was measured by immunoassay (CLIA) and not by mass spectrometry, thus permitting comparison.

The relevance of this finding is highlighted by the study of Morote and colleagues demonstrating that for approx. 50% of those patients with a testosterone level below 0.2 ng/dL measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS), CLIA testing yields levels between 0.2 and 0.5 ng/mL.4 While there is consensus, that low levels of testosterone are related to improved survival and are therefore mandatory, an indirect comparison of trial results using different analytical methods and/or setups does not allow any helpful conclusions.

Finally, we consider it encouraging that more than 95% of the indications in this study were in line with recommendations for ADT use in the German S3 guidelines, indicating a high level of guideline adherence, also in routine clinical practice.3

Written by: Bernd J Schmitz-Dräger, Stephan Mühlich, Carsten Lange, Natalya Benderska-Söder, Ekkehardt Bismarck, Roland Starlinger, Bertram Ottillinger, Oliver W Hakenberg

Urologie 24, Nuremberg, Germany, ., Urological Practice, Bamberg, Germany., Schwerpunktpraxis Urologie, Bernburg, Germany., Urologie 24, Nuremberg, Germany., Global Medical Affairs, Sandoz International GmbH, Holzkirchen, Germany., Ottillinger Life Sciences, Brunnthal, Germany., Department of Urology, Rostock University, Rostock, Germany.


  1. Schmitz-Dräger BJ, Mühlich S, Lange C, Benderska-Söder N, Bismarck E, Starlinger R, Ottillinger B, Hakenberg O. Effectiveness and distribution of testosterone levels within first year of androgen deprivation therapy in a real-world setting – results from the non-interventional German cohort LEAN study. Urol Int. 2021 Feb 25:1-10
  2. https://www.nccn.org/store/login/login.aspx?ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf
  3. Interdisziplinäre Leitlinie der Qualität S3 zur Früherkennung, Diagnose und Therapie der verschiedenen Stadien des Prostatakarzinoms, AWMF Registernummer: 043/022OL, http://www.leitlinienprogramm-onkologie.de/leitlinien/prostatakarzinom/
  4. Morote J, Comas I, Planas J, Maldonado X, Celma A, Placer J, Ferrer R, Carles J, Regis L. Serum Testosterone Levels in Prostate Cancer Patients Undergoing Luteinizing Hormone-Releasing Hormone Agonist Therapy. Clin Genitourin Cancer. 2018 Apr;16(2):e491-e496.

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