Andrea Necchi1, Salvatore Lo Vullo1, Luigi Mariani1, Marco Moschini2, Kees Hendricksen3, Michael Rink4, Roman Sosnowski5, Jakub Dobruch6, Jay D Raman7, Christopher G Wood8, Vitaly Margulis9, Morgan Roupret10,11, Alberto Briganti2, Francesco Montorsi2, Evanguelos Xylinas12, Shahrokh F Shariat13. 1. Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 2. Department of Urology, IRCCS San Raffaele Hospital, Vita Salute San Raffaele University, Milan, Italy. 3. Netherlands Cancer Institute, Amsterdam, The Netherlands. 4. Department of Urology, University Medical Centre, Hamburg-Eppendorf, Hamburg, Germany. 5. Centre of Postgraduate Medical Education, European Health Centre Otwock, Warsaw, Poland. 6. M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland. 7. Division of Urology, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA. 8. Department of Urology, UT M.D. Anderson Cancer Center, Houston, TX, USA. 9. Department of Urology, UT Southwestern Medical Center, Dallas, TX, USA. 10. Academic Department of Urology, Pitié-Salpétrière Hospital, Assistance-Publique Hôpitaux de Paris, Paris, France. 11. Pierre et Marie Curie Medical School, University Paris 6, Paris, France. 12. Cochin Hospital, Assistance-Publique Hôpitaux de Paris, Paris Descartes University, Paris, France. 13. Medical University of Vienna, Vienna, Austria.
Abstract
OBJECTIVE: To analyse the outcomes of adjuvant chemotherapy vs observation in a multicentre cohort of patients with upper tract urothelial carcinoma (UTUC) in order to clarify whether such patients benefit from adjuvant chemotherapy after radical nephroureterectomy (RNU). PATIENTS AND METHODS: Data from 15 centres were collected for a total of 1544 patients, treated between 2000 and 2015. Criteria for patient selection included pT2-4N0/x stage, or lymph node-positive disease, and prior RNU. The standardized difference approach was used to compare subgroup characteristics. Overall survival (OS) was the primary endpoint. The primary analysis used 1:1 propensity score matching, with inverse probability of treatment weighting in addition to this in the secondary analysis. The latter was also performed with the inclusion of covariates, i.e. with 'doubly robust' estimation. A 6-month landmark analysis was performed to exclude early events. RESULTS: A total of 312 patients received adjuvant chemotherapy and 1232 underwent observation. Despite differences between the two groups, the standardized difference was generally <10% after matching. In the matched analysis no difference was observed in OS between adjuvant chemotherapy and observation (hazard ratio [HR] 1.14, 95% confidence inverval [CI] 0.91-1.43; P = 0.268). In the doubly robust estimate-adjusted comparison, adjuvant chemotherapy was significantly associated with shorter OS (HR 1.26, 95% CI 1.02-1.54; P = 0.032). Similar findings were confirmed in subgroup analyses stratified by pathological stage, and after landmark analysis. Results should be interpreted with consideration given to the inherent limitations of retrospective studies. CONCLUSION: Adjuvant chemotherapy did not improve OS compared with observation in the present study. These results contribute to the uncertainties regarding postoperative chemotherapy in UTUC, and suggest dedicated prospective trials, new more potent therapies, and the identification of enhanced patient selection criteria are required.
OBJECTIVE: To analyse the outcomes of adjuvant chemotherapy vs observation in a multicentre cohort of patients with upper tract urothelial carcinoma (UTUC) in order to clarify whether such patients benefit from adjuvant chemotherapy after radical nephroureterectomy (RNU). PATIENTS AND METHODS: Data from 15 centres were collected for a total of 1544 patients, treated between 2000 and 2015. Criteria for patient selection included pT2-4N0/x stage, or lymph node-positive disease, and prior RNU. The standardized difference approach was used to compare subgroup characteristics. Overall survival (OS) was the primary endpoint. The primary analysis used 1:1 propensity score matching, with inverse probability of treatment weighting in addition to this in the secondary analysis. The latter was also performed with the inclusion of covariates, i.e. with 'doubly robust' estimation. A 6-month landmark analysis was performed to exclude early events. RESULTS: A total of 312 patients received adjuvant chemotherapy and 1232 underwent observation. Despite differences between the two groups, the standardized difference was generally <10% after matching. In the matched analysis no difference was observed in OS between adjuvant chemotherapy and observation (hazard ratio [HR] 1.14, 95% confidence inverval [CI] 0.91-1.43; P = 0.268). In the doubly robust estimate-adjusted comparison, adjuvant chemotherapy was significantly associated with shorter OS (HR 1.26, 95% CI 1.02-1.54; P = 0.032). Similar findings were confirmed in subgroup analyses stratified by pathological stage, and after landmark analysis. Results should be interpreted with consideration given to the inherent limitations of retrospective studies. CONCLUSION: Adjuvant chemotherapy did not improve OS compared with observation in the present study. These results contribute to the uncertainties regarding postoperative chemotherapy in UTUC, and suggest dedicated prospective trials, new more potent therapies, and the identification of enhanced patient selection criteria are required.
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