Pathological downstaging and survival after induction chemotherapy and radical cystectomy for clinically node-positive bladder cancer-Results of a nationwide population-based study.
Induction chemotherapy (IC) for clinically node-positive bladder cancer is applied without clinical evidence of improved outcome. Our objective was to compare complete pathological downstaging (pCD) and overall survival (OS) for IC versus upfront radical cystectomy (RC) in cT1-4aN1-3M0 urothelial carcinoma (UC).



This population-based study included 659 cN+ patients treated with RC between 1995 and 2013. IC was applied in 212 (32%) patients. We defined pCD as ≤(y)pT1N0 at RC. Multivariable analyses were preformed to identify independent predictors of pCD and OS.



In cN1 and cN2-3 patients, 31% and 19% of patients proved to be pN0 at upfront RC. In cN1, pCD was achieved in 39% following IC versus 5% for upfront RC (P < 0.001). In cN2-3 UC, rates were 27% versus 3% (P < 0.001). Three-year OS for pCD and ypCD were 81% and 84%, respectively. Three-year OS rates were 66% versus 37% (cN1) and 43% versus 22% (cN2-3), again in favour of IC (P < 0.001). In multivariable analyses, IC was associated with pCD (Odds ratio, 14; 95% confidence interval [CI], 7.4-25) and a 53% decreased risk of death (Hazard ratio [HR], 0.47; 95% CI, 0.36-0.61). Indication bias and unequal distributions of factors associated with OS (e.g. patients proceeding to RC) limit interpretation of our results.



Patients with clinical nodal involvement should not be neglected. Up to 1/4 of patients with cN+ disease had pN0 at upfront RC. Moreover, IC followed by RC for clinically node-positive UC was associated with improved pathological downstaging compared with RC alone. A potential OS benefit for IC needs to be validated in a randomised trial.



IC followed by RC for clinically node-positive UC is associated with improved pathological downstaging compared with RC alone. A potential OS benefit for IC needs to be validated in a randomised trial.
Department of Surgical Oncology, Division of Urology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Tom J N
TJ
Hermans
Department of Surgical Oncology, Division of Urology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Elisabeth E
EE
Fransen van de Putte
Department of Surgical Oncology, Division of Urology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Simon
S
Horenblas
Department of Urology, University Medical Center Utrecht, Utrecht, The Netherlands.
Richard P
RP
Meijer
Department of Urology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Joost L
JL
Boormans
Department of Research, Netherlands Comprehensive Cancer Organization, Utrecht, The Netherlands; Radboud Institute for Health Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.
Katja K H
KK
Aben
Department of Medical Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Michiel S
MS
van der Heijden
Department of Medical Oncology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Ronald
R
de Wit
Department of Medical Oncology, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands.
Laurens V
LV
Beerepoot
Department of Research, Netherlands Comprehensive Cancer Organization, Utrecht, The Netherlands.
Rob H A
RH
Verhoeven
Department of Surgical Oncology, Division of Urology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. Electronic address: basvanrhijn@hotmail.com.
Bas W G
BW
van Rhijn
D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D015653:Cystectomy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008198:Lymph Nodes / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009426:Netherlands; D016017:Odds Ratio; D016016:Proportional Hazards Models; D012042:Registries; D015996:Survival Rate; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*
Bladder; Cancer; Chemotherapy; Induction; Neoadjuvant; Survival