Gregory R Pond1, Giuseppe Di Lorenzo2, Andrea Necchi3, Bernhard J Eigl4, Michael P Kolinsky5, Raju T Chacko6, Tanya B Dorff7, Lauren C Harshman8, Matthew I Milowsky9, Richard J Lee10, Matthew D Galsky11, Piera Federico2, Graeme Bolger12, Mollie DeShazo12, Amitkumar Mehta12, Jatinder Goyal13, Guru Sonpavde14. 1. McMaster University, Hamilton, Ontario, Canada. 2. University Federico II, Napoli, Italy. 3. Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. 4. BC Cancer Agency, Vancouver, British Columbia, Canada. 5. University of Alberta, Edmonton, Alberta, Canada. 6. Christian Medical College, Vellore, Tamil Nadu, India. 7. University of Southern California, Los Angeles CA. 8. Dana-Farber Cancer Institute, Boston, MA. 9. University of North Carolina, Chapel Hill, NC. 10. Masachussetts General Hospital Cancer Center, Boston, MA. 11. Mt Sinai Tisch Cancer Institute, New York, NY. 12. University of Alabama at Birmingham (UAB) Comprehensive Cancer Center, Birmingham, AL. 13. Department of Medicine, UAB Medical Center, Birmingham, AL. 14. University of Alabama at Birmingham (UAB) Comprehensive Cancer Center, Birmingham, AL. Electronic address: gsonpavde@uabmc.edu.
Abstract
BACKGROUND: Prognostic factors in men with penile squamous cell carcinoma (PSCC) receiving systemic therapy are unknown. A prognostic classification system in this disease may facilitate interpretation of outcomes and guide rational drug development. We performed a retrospective analysis to identify prognostic factors in men with PSCC receiving first-line systemic therapy for advanced disease. PATIENTS AND METHODS: Individual patient level data were obtained from 13 institutions to study prognostic factors in the context of first-line systemic therapy for advanced PSCC. Cox proportional hazards regression analysis was conducted to examine the prognostic effect of these candidate factors on progression-free survival (PFS) and overall survival (OS): age, stage, hemoglobin, neutrophil count, lymphocyte count, albumin, site of metastasis (visceral or nonvisceral), smoking, circumcision, regimen, ECOG performance status (PS), lymphovascular invasion, precancerous lesion, and surgery following chemotherapy. The effect of different treatments was then evaluated adjusting for factors in the prognostic model. RESULTS: The study included 140 eligible men. Mean age across all men was 57.0 years. Among them, 8.6%, 21.4%, and 70.0% of patients had stage 2, 3, and 4 diseases, respectively; 40.7% had ECOG PS ≥ 1, 47.4% had visceral metastases, and 73.6% received cisplatin-based chemotherapy. The multivariate model of poor prognostic factors included visceral metastases (P<0.001) and ECOG PS ≥ 1 (P<0.001) for both PFS and OS. A risk stratification model constructed with 0, 1, and both poor prognostic factors was internally validated and demonstrated moderate discriminatory ability (c-statistic of 0.657 and 0.677 for OS and PFS, respectively). The median OS for the entire population was 9 months. Median OS was not reached, 8, and 7 months for those with 0, 1, and both risk factors, respectively. Cisplatin-based regimens were associated with better OS (P = 0.017) but not PFS (P = 0.37) compared with noncisplatin-based regimens after adjusting for the 2 prognostic factors. CONCLUSIONS: In men with advanced PSCC receiving first-line systemic therapy, visceral metastases and ECOG PS ≥ 1 were poor prognostic factors. A prognostic model including these factors exhibited moderate discriminatory ability for outcomes and warrants external validation. Patients receiving cisplatin-based regimens exhibited better outcomes compared with noncisplatin-based regimens after adjusting for prognostic factors.
BACKGROUND: Prognostic factors in men with penile squamous cell carcinoma (PSCC) receiving systemic therapy are unknown. A prognostic classification system in this disease may facilitate interpretation of outcomes and guide rational drug development. We performed a retrospective analysis to identify prognostic factors in men with PSCC receiving first-line systemic therapy for advanced disease. PATIENTS AND METHODS: Individual patient level data were obtained from 13 institutions to study prognostic factors in the context of first-line systemic therapy for advanced PSCC. Cox proportional hazards regression analysis was conducted to examine the prognostic effect of these candidate factors on progression-free survival (PFS) and overall survival (OS): age, stage, hemoglobin, neutrophil count, lymphocyte count, albumin, site of metastasis (visceral or nonvisceral), smoking, circumcision, regimen, ECOG performance status (PS), lymphovascular invasion, precancerous lesion, and surgery following chemotherapy. The effect of different treatments was then evaluated adjusting for factors in the prognostic model. RESULTS: The study included 140 eligible men. Mean age across all men was 57.0 years. Among them, 8.6%, 21.4%, and 70.0% of patients had stage 2, 3, and 4 diseases, respectively; 40.7% had ECOG PS ≥ 1, 47.4% had visceral metastases, and 73.6% received cisplatin-based chemotherapy. The multivariate model of poor prognostic factors included visceral metastases (P<0.001) and ECOG PS ≥ 1 (P<0.001) for both PFS and OS. A risk stratification model constructed with 0, 1, and both poor prognostic factors was internally validated and demonstrated moderate discriminatory ability (c-statistic of 0.657 and 0.677 for OS and PFS, respectively). The median OS for the entire population was 9 months. Median OS was not reached, 8, and 7 months for those with 0, 1, and both risk factors, respectively. Cisplatin-based regimens were associated with better OS (P = 0.017) but not PFS (P = 0.37) compared with noncisplatin-based regimens after adjusting for the 2 prognostic factors. CONCLUSIONS: In men with advanced PSCC receiving first-line systemic therapy, visceral metastases and ECOG PS ≥ 1 were poor prognostic factors. A prognostic model including these factors exhibited moderate discriminatory ability for outcomes and warrants external validation. Patients receiving cisplatin-based regimens exhibited better outcomes compared with noncisplatin-based regimens after adjusting for prognostic factors.
Authors: Carlo Buonerba; Giuseppe Di Lorenzo; Gregory Pond; Giacomo Cartenì; Sarah Scagliarini; Antonio Rozzi; Fernando J Quevedo; Tanya Dorff; Lucia Nappi; Gaetano Lanzetta; Lance Pagliaro; Bernhard J Eigl; Gurudatta Naik; Matteo Ferro; Mariano Galdiero; Sabino De Placido; Guru Sonpavde Journal: Front Pharmacol Date: 2016-12-20 Impact factor: 5.810
Authors: Eddy S Yang; Christopher D Willey; Amitkumar Mehta; Michael R Crowley; David K Crossman; Dongquan Chen; Joshua C Anderson; Gurudatta Naik; Deborah L Della Manna; Tiffiny S Cooper; Guru Sonpavde Journal: Oncotarget Date: 2017-03-28
Authors: Carlos E Stecca; Marie Alt; Di Maria Jiang; Peter Chung; Juanita M Crook; Girish S Kulkarni; Srikala S Sridhar Journal: Oncol Ther Date: 2021-01-16