title: Prognostic risk stratification derived from individual patient level data for men with advanced penile squamous cell carcinoma receiving first-line systemic therapy.
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.
  
  
  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: McMaster University, Hamilton, Ontario, Canada.
authors: Gregory R
authors: GR
authors: Pond
authors: University Federico II, Napoli, Italy.
authors: Giuseppe
authors: G
authors: Di Lorenzo
authors: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors: Andrea
authors: A
authors: Necchi
authors: BC Cancer Agency, Vancouver, British Columbia, Canada.
authors: Bernhard J
authors: BJ
authors: Eigl
authors: University of Alberta, Edmonton, Alberta, Canada.
authors: Michael P
authors: MP
authors: Kolinsky
authors: Christian Medical College, Vellore, Tamil Nadu, India.
authors: Raju T
authors: RT
authors: Chacko
authors: University of Southern California, Los Angeles CA.
authors: Tanya B
authors: TB
authors: Dorff
authors: Dana-Farber Cancer Institute, Boston, MA.
authors: Lauren C
authors: LC
authors: Harshman
authors: University of North Carolina, Chapel Hill, NC.
authors: Matthew I
authors: MI
authors: Milowsky
authors: Masachussetts General Hospital Cancer Center, Boston, MA.
authors: Richard J
authors: RJ
authors: Lee
authors: Mt Sinai Tisch Cancer Institute, New York, NY.
authors: Matthew D
authors: MD
authors: Galsky
authors: University Federico II, Napoli, Italy.
authors: Piera
authors: P
authors: Federico
authors: University of Alabama at Birmingham (UAB) Comprehensive Cancer Center, Birmingham, AL.
authors: Graeme
authors: G
authors: Bolger
authors: University of Alabama at Birmingham (UAB) Comprehensive Cancer Center, Birmingham, AL.
authors: Mollie
authors: M
authors: DeShazo
authors: University of Alabama at Birmingham (UAB) Comprehensive Cancer Center, Birmingham, AL.
authors: Amitkumar
authors: A
authors: Mehta
authors: Department of Medicine, UAB Medical Center, Birmingham, AL.
authors: Jatinder
authors: J
authors: Goyal
authors: University of Alabama at Birmingham (UAB) Comprehensive Cancer Center, Birmingham, AL. Electronic address: gsonpavde@uabmc.edu.
authors: Guru
authors: G
authors: Sonpavde
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D003131:Combined Modality Therapy; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010412:Penile Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D057285:Precision Medicine; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods*; D015996:Survival Rate
keywords: Advanced; Penile squamous cell carcinoma; Prognosis; Systemic therapy