title: The presence of carcinoma in situ at radical cystectomy increases the risk of urothelial recurrence: Implications for follow-up schemes.
abstract: To evaluate the incidence of carcinoma in situ (CIS) in patients treated with radical cystectomy (RC) due to bladder cancer and to assess its effect on recurrence and survival rates.
  
  
  
  The study focused on 1,128 consecutive nonmetastatic patients with bladder cancer treated with RC at a single tertiary care referral center from 1994 to 2014. The Kaplan-Meier method was used to compare recurrence, cancer-specific mortality (CSM), and overall mortality-free rates in the overall population and in pT0-pT2 and pT3-pT4 patients after stratifying according to the presence of CIS. Multivariable (MVA) Cox regression analyses tested the effect of the presence of CIS on survival outcomes. MVA competing risk analyses were performed to assess the effect of CIS on urothelial recurrence.
  
  
  
  The presence of CIS was reported in 277 (24.6%) patients. During a median follow-up of 6 years, 355 recurrences, 377 CSM, and 468 overall mortality were reported. At MVA Cox regression analyses, the presence of concomitant CIS was not associated with any survival effect when the overall population was considered (all P≥0.3). At MVA Cox regression analyses, there was no effect of CIS on survival outcomes in pT3-pT4 patients (all P>0.2); on the contrary, the presence of CIS was associated with worse CSM in pT0-pT2 patients only (hazard ratio [HR] = 1.82; CI: 1.01-3.29; P = 0.04). At MVA competing risk analyses predicting urothelial recurrence only, the presence of CIS was associated to an increased risk of urothelial recurrence in pT0-pT2 patients (HR = 2.99; CI: 1.05-8.53; P = 0.04), pT3-pT4 patients (HR = 10.29; CI: 1.40-75.75; P = 0.02), and in the overall population (HR = 4.47; CI: 1.81-11.07; P = 0.001).
  
  
  
  An increased risk of developing urothelial recurrence only was recorded in patients diagnosed with CIS at RC. Physicians should consider this aspect ensuring a more severe follow-up schemes in patients who harbored this pathological feature.
authors.affiliation: Unit of Urology, Division of Oncology, IRCCS Ospedale San Raffaele, URI Milan, Italy; Department of Urology, Magna Graecia University of Catanzaro, Catanzaro, Italy; Department of Urology, Medical University of Vienna, Vienna, Austria. Electronic address: marco.moschini87@gmail.com.
authors.forename: Marco
authors.initials: M
authors.lastname: Moschini
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna, Austria.
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna, Austria.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Abufaraj
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna, Austria.
authors.forename: Francesco
authors.initials: F
authors.lastname: Soria
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna, Austria.
authors.forename: Tobias
authors.initials: T
authors.lastname: Klatte
authors.affiliation: Unit of Urology, Division of Oncology, IRCCS Ospedale San Raffaele, URI Milan, Italy.
authors.forename: Giovanni La
authors.initials: G
authors.lastname: Croce
authors.affiliation: Klinik für Urologie, Luzerner Kantonsspital, Lucerne, Switzerland.
authors.forename: Agostino
authors.initials: A
authors.lastname: Mattei
authors.affiliation: Department of Urology, Magna Graecia University of Catanzaro, Catanzaro, Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: Damiano
authors.affiliation: Unit of Urology, Division of Oncology, IRCCS Ospedale San Raffaele, URI Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Salonia
authors.affiliation: Unit of Urology, Division of Oncology, IRCCS Ospedale San Raffaele, URI Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.affiliation: Unit of Urology, Division of Oncology, IRCCS Ospedale San Raffaele, URI Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Briganti
authors.affiliation: Unit of Urology, Division of Oncology, IRCCS Ospedale San Raffaele, URI Milan, Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Colombo
authors.affiliation: Unit of Urology, Division of Oncology, IRCCS Ospedale San Raffaele, URI Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gallina
mesh_terms: D000368:Aged; D002278:Carcinoma in Situ / Q000473:pathology*; D015653:Cystectomy / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008197:Lymph Node Excision / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000453:epidemiology* / Q000601:surgery; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000601:surgery*
keywords: Bladder cancer; Cancer-specific survival; Carcinoma in situ; Radical cystectomy; Recurrence; pTis