title: Contemporary management of regional nodes in penile cancer-improvement of survival?
abstract: OBJECTIVE
  The management of regional nodes of penile squamous cell carcinoma has changed with time due to improved knowledge about diagnosis and treatment. To determine whether changes in the treatment of regional nodes have improved survival, we compared contemporary 5-year cancer specific survival of patients with squamous cell carcinoma of the penis with that of patients in previous cohorts.
  
  
  METHODS
  In an observational cohort study of 1,000 patients treated during 56 years 944 were eligible for analysis. Tumors were staged according to the 2009 TNM classification, and patients were divided into 4 cohorts of 1956 to 1987, 1988 to 1993, 1994 to 2000 and 2001 to 2012, reflecting changes in clinical practice regarding regional nodes. Kaplan-Meier survival curves with the log rank test and Cox proportional hazards modeling were used to examine trends in 5-year cancer specific survival.
  
  
  RESULTS
  The 5-year cancer specific survival of patients with cN0 disease treated between 2001 and 2012 was 92% compared to 89% (1994 to 2000), 78% (1988 to 1993) and 85% (1956 to 1987). The 5-year cancer specific survival improved significantly since 1994, the year dynamic sentinel node biopsy was introduced, at 91% (1994 to 2012) vs 82% (1956 to 1993) (p = 0.021). This conclusion still holds after adjustment for pathological T stage and grade of differentiation (HR 2.46, p = 0.01). Extranodal extension, number of tumor positive nodes and pelvic involvement in node positive (pN+) cases were associated with worse 5-year cancer specific survival.
  
  
  CONCLUSIONS
  Despite less surgery being performed on regional nodes, 5-year cancer specific survival has improved in patients with cN0 disease. The number of tumor positive nodes, extranodal extension and pelvic involvement were highly associated with worse cancer specific survival in patients with pN+ disease. In this group other treatment strategies are needed as no improvement was observed.
authors.affiliation: Department of Urology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Rosa S
authors.initials: RS
authors.lastname: Djajadiningrat
authors.affiliation: Department of Urology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Niels M
authors.initials: NM
authors.lastname: Graafland
authors.affiliation: Department of Biometrics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: van Werkhoven
authors.affiliation: Department of Urology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Meinhardt
authors.affiliation: Department of Urology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Axel
authors.initials: A
authors.lastname: Bex
authors.affiliation: Department of Urology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Henk G
authors.initials: HG
authors.lastname: van der Poel
authors.affiliation: Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Hester H
authors.initials: HH
authors.lastname: van Boven
authors.affiliation: Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Renato A
authors.initials: RA
authors.lastname: Valdés Olmos
authors.affiliation: Department of Urology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address: s.horenblas@nki.nl.
authors.forename: Simon
authors.initials: S
authors.lastname: Horenblas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D015331:Cohort Studies; D006119:Groin; D006801:Humans; D053208:Kaplan-Meier Estimate; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010412:Penile Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D016016:Proportional Hazards Models; D021701:Sentinel Lymph Node Biopsy; D055815:Young Adult
keywords: CSS; DSNB; ENE; SCCp; cancer specific survival; carcinoma; dynamic sentinel node biopsy; extranodal extension; iLND; inguinal lymph node dissection; lymphatic metastasis; penile neoplasms; sentinel lymph node biopsy; squamous cell; squamous cell carcinoma of the penis; survival