Time to testosterone recovery (TR) following androgen deprivation therapy (ADT) with gonadotropin-releasing hormone agonists varies widely. We evaluate TR kinetics and the oncological impact of an effective castration period in patients receiving definitive radiotherapy and ADT for prostate cancer.
We obtained individual patient data from randomized controlled trials of radiotherapy with ADT and prospectively collected serial testosterone data from the MARCAP Consortium. We estimated the times to noncastrate TR (>1.7 nmol/l) and nonhypogonadal TR (>8.0 nmol/l) were estimated for each prescribed ADT duration, and developed corresponding nomograms. The association between effective castration period and metastasis-free survival (MFS) for any given ADT duration was evaluated via multivariable Cox regression. We conducted cubic spline analyses to assess nonlinear associations.
We included 1444 men from five trials in the analysis, of whom 115 received 4 mo, 880 received 6 mo, 353 received 18 mo, 36 received 28 mo, and 60 received 36 mo of ADT. Times to noncastrate TR and to nonhypogonadal TR varied considerably by ADT duration. Higher baseline testosterone and lower age were associated with a higher likelihood of TR (p < 0.001 for both). Effective castration period was not linearly associated with MFS for any ADT duration on Cox regression. Cubic spline analysis revealed that the optimal effective castration period for an MFS benefit was 10.6 mo for men who received 6 mo of ADT and 18 mo for men who received 18 mo of ADT.
Time to TR varies according to the ADT duration, baseline testosterone, and age. The relationship between effective castration period and MFS may be nonlinear, with a longer effective castration period being helpful for men receiving 6 mo of ADT.
European urology. 2024 Sep 19 [Epub ahead of print]
Wee Loon Ong, Tahmineh Romero, Soumyajit Roy, John Nikitas, David Joseph, Almudena Zapatero, Shawn Malone, Scott C Morgan, Michael L Steinberg, Luca F Valle, Nicholas G Zaorsky, Ting Martin Ma, Matthew B Rettig, Nicholas Nickols, Tommy Jiang, Robert E Reiter, Sriram V Eleswarapu, Xavier Maldonado, Yilun Sun, Paul L Nguyen, Jeremy L Millar, Jarad M Martin, Daniel E Spratt, Amar U Kishan, MARCAP Consortium Investigators
Alfred Health Radiation Oncology, Monash University, Melbourne, Australia., Division of General Internal Medicine and Health Services Research, University of California-Los Angeles, Los Angeles, CA, USA., Department of Radiation Oncology, Rush University Medical Centre, Chicago, IL, USA., Department of Radiation Oncology, University of California-Los Angeles, Los Angeles, CA, USA., Department of Medicine and Surgery, University of Western Australia, Perth, Australia., Department of Radiation Oncology, Health Research Institute, Hospital Universitario de la Princesa, Madrid, Spain., Department of Radiology, Radiation Oncology and Medical Physics, Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, Canada., Department of Radiation Oncology, University Hospitals Seidman Cancer Centre, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Department of Radiation Oncology, University of Washington, Seattle, WA, USA., Department of Medical Oncology, University of California-Los Angeles, Los Angeles, CA, USA., Department of Urology, University of California-Los Angeles, Los Angeles, CA, USA., Hospital Universitari Vall d'Hebron, Barcelona, Spain., Department of Radiation Oncology, University Hospitals Seidman Cancer Centre, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Department of Population Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA., Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Department of Radiation Oncology, Calvary Mater Newcastle Hospital, University of Newcastle, Newcastle, Australia., Department of Radiation Oncology, University of California-Los Angeles, Los Angeles, CA, USA. Electronic address: .