Radiotherapy (RT) and long-term androgen deprivation therapy (ltADT; 18-36 mo) is a standard of care in the treatment of high-risk localized/locoregional prostate cancer (HRLPC). We evaluated the outcomes in patients treated with RT + ltADT to identify which patients have poorer prognosis with standard therapy.
Individual patient data from patients with HRLPC (as defined by any of the following three risk factors [RFs] in the context of cN0 disease-Gleason score ≥8, cT3-4, and prostate-specific antigen [PSA] >20 ng/ml, or cN1 disease) treated with RT and ltADT in randomized controlled trials collated by the Intermediate Clinical Endpoints in Cancer of the Prostate group. The outcome measures of interest were metastasis-free survival (MFS), overall survival (OS), time to metastasis, and prostate cancer-specific mortality. Multivariable Cox and Fine-Gray regression estimated hazard ratios (HRs) for the three RFs and cN1 disease.
A total of 3604 patients from ten trials were evaluated, with a median PSA value of 24 ng/ml. Gleason score ≥8 (MFS HR = 1.45; OS HR = 1.42), cN1 disease (MFS HR = 1.86; OS HR = 1.77), cT3-4 disease (MFS HR = 1.28; OS HR = 1.22), and PSA >20 ng/ml (MFS HR = 1.30; OS HR = 1.21) were associated with poorer outcomes. Adjusted 5-yr MFS rates were 83% and 78%, and 10-yr MFS rates were 63% and 53% for patients with one and two to three RFs, respectively; corresponding 10-yr adjusted OS rates were 67% and 60%, respectively. In cN1 patients, adjusted 5- and 10-yr MFS rates were 67% and 36%, respectively, and 10-yr OS was 47%.
HRLPC patients with two to three RFs (and cN0) or cN1 disease had the poorest outcomes on RT and ltADT. This will help in counseling patients treated in routine practice and in guiding adjuvant trials in HRLPC.
Radiotherapy and long-term hormone therapy are standard treatments for high-risk and locoregional prostate cancer. In this report, we defined prognostic groups within high-risk/locoregional prostate cancer and showed that outcomes to standard therapy are poorest in those with two or more "high-risk" factors or evidence of lymph node involvement. Such patients may therefore be the best candidates for intensification of treatment.
European urology. 2024 May 21 [Epub ahead of print]
Praful Ravi, Wanling Xie, Marc Buyse, Susan Halabi, Philip W Kantoff, Oliver Sartor, Gert Attard, Noel Clarke, Anthony D'Amico, James Dignam, Nicholas James, Karim Fizazi, Silke Gillessen, Wendy Parulekar, Howard Sandler, Daniel E Spratt, Matthew R Sydes, Bertrand Tombal, Scott Williams, Christopher J Sweeney
Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: ., Dana-Farber Cancer Institute, Boston, MA, USA., International Drug Development Institute, Louvain-la-Neuve, Belgium; I-BioStat, Hasselt University, Hasselt, Belgium., Duke University, Durham, NC, USA., Convergent Therapeutics, Cambridge, MA, USA; Memorial Sloan Kettering Cancer Center, New York, NY, USA., Mayo Clinic, Rochester, MN, USA., University College London, London, UK., The Christie NHS Foundation Trust, Manchester, UK., Dana-Farber Cancer Institute, Boston, MA, USA; Brigham & Women's Hospital, Boston, MA, USA., University of Chicago, Chicago, IL, USA., The Institute of Cancer Research & The Royal Marsden NHS Foundation Trust, London, UK., Institut Gustave Roussy, University of Paris Saclay, Villejuif, France., Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland; Università della Svizzera Italiana, Lugano, Switzerland., Queens University, Kingston, Ontario, Canada., Cedars-Sinai Medical Center, Los Angeles, CA, USA., University Hospitals Siedman Cancer Center, Case Western Reserve University, Cleveland, OH, USA., MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK., Cliniques Universitaires Saint-Luc, Brussels, Belgium., Peter Maccallum Cancer Centre, Melbourne, Australia., South Australian Immunogenomics Cancer Institute, University of Adelaide, Adelaide, Australia. Electronic address: .