Risk stratification of prostate cancer through quantitative assessment of PTEN loss (qPTEN).

PTEN loss has long been associated with adverse findings in early prostate cancer. Studies to date have yet to employ quantitative methods (qPTEN) for measuring of prognostically relevant amount of PTEN loss in post-surgical setting and demonstrate its clinical application.

PTEN protein levels were measured by immunohistochemistry in radical prostatectomy (RP) samples from training (n = 410) and validation (n = 272) cohorts. PTEN loss was quantified per cancer cell and per tissue microarray core. Thresholds for identifying clinically relevant PTEN loss were determined using log-rank statistics in the training cohort. Univariate (Kaplan-Meier) and multivariate (Cox's proportional hazards) analyses on various subpopulations were performed to assess biochemical recurrence free survival and were independently validated. All statistical tests were two-sided.

PTEN loss in > 65% cancer cells was most clinically relevant and had statistically significant association with reduced biochemical recurrence free survival (BRFS) in training (HR = 2.48, 95% CI = 1.59 to 3.87, p < 0.001) and validation cohorts (HR = 4.22, 95% CI = 2.01 to 8.83, p < 0.001). qPTEN scoring method identified patients who recurred within 5.4 yrs after surgery (p < 0.001). In men with favorable risk of BCR (CAPRA-S scores <5 and no adverse pathological features), qPTEN identified a subset of patients with shorter BRFS (HR = 5.52, 95% CI = 2.36 to 12.90, p < 0.001) who may be considered for intensified monitoring and/or adjuvant therapy.

Compared to previous qualitative approaches, qPTEN improves risk stratification of post-RP patients and may be considered as a complementary tool to guide disease management after surgery.

Journal of the National Cancer Institute. 2020 Mar 04 [Epub ahead of print]

Tamara Jamaspishvili, Palak G Patel, Yi Niu, Thiago Vidotto, Isabelle Caven, Rachel Livergant, Winnie Fu, Atsunari Kawashima, Nathan How, John B Okello, Liana B Guedes, Veronique Ouellet, Clarissa Picanço, Madhuri Koti, Rodolfo B Reis, Fred Saad, Anne-Marie Mes-Masson, Tamara L Lotan, Jeremy A Squire, Yingwei P Peng, D Robert Siemens, David M Berman

Divisions of Cancer Biology & Genetics, Queen's Cancer Research Institute, Kingston, ON, Canada., Divisions of Cancer Care and Epidemiology, Queen's Cancer Research Institute, Kingston, ON, Canada., Departments of Pathology, Johns Hopkins University, Baltimore, MD, USA., Institut du cancer de Montréal and Centre de recherche du Centre hospitalier de l'Université de Montréal, Montréal, Québec, Canada., Departments of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Departments of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Departments of Urology, Queen's University, Kingston, ON, Canada.