Sabine D Brookman-May1, Matthias May2, Ingmar Wolff3, Richard Zigeuner4, Georg C Hutterer4, Luca Cindolo5, Luigi Schips5, Ottavio De Cobelli6, Bernardo Rocco7, Cosimo De Nunzio8, Andrea Tubaro8, Ioman Coman9, Michael Truss10, Orietta Dalpiaz11, Bogdan Feciche12, Robert S Figenshau13, Kerry Madison13, Manuel Sánchez-Chapado14, Maria del Carmen Santiago Martin14, Luigi Salzano15, Giuseppe Lotrecchiano15, Stefan Zastrow16, Manfred Wirth16, Petros Sountoulides13, Shahrokh Shariat17, Raphaela Waidelich18, Christian Stief18, Sven Gunia19. 1. Department of Urology, Ludwig Maximilians University, Munich, Germany; Janssen Pharma Research and Development, Beerse, Belgium. Electronic address: sabine.brookman-may@email.de. 2. Department of Urology, St. Elisabeth Hospital Straubing, Straubing, Germany. 3. Department of Urology, Carl Thiem Klinikum, Cottbus, Germany. 4. Department of Urology, Medical University of Graz, Graz, Austria. 5. Department of Urology, Pio Da Pietrelcina Hospital, Vasto, Italy. 6. Division of Urology, European Institute of Oncology, Milan, Italy. 7. Department of Urology, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy. 8. Department of Urology, Faculty of Health Sciences, University La Sapienza, Rome, Italy. 9. Department of Urology, Clinical Municipal Hospital, Cluj-Napoca, Romania. 10. Department of Urology, Klinikum Dortmund, Dortmund, Germany. 11. Department of Urology, Carl Thiem Klinikum, Cottbus, Germany; Department of Urology, Klinikum Dortmund, Dortmund, Germany. 12. Department of Urology, Emergency Hospital Satu Mare, Satu Mare, Romania. 13. Division of Urologic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA. 14. Department of Urology, Hospital Universitario Principe de Asturias, Madrid, Spain. 15. Department of Urology, G. Rummo Hospital, Benevento, Italy. 16. Department of Urology, Carl Gustav Carus University, Dresden, Germany. 17. Department of Urology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria. 18. Department of Urology, Ludwig Maximilians University, Munich, Germany; Janssen Pharma Research and Development, Beerse, Belgium. 19. Department of Pathology, Johanniter Hospital Stendal, Stendal, Germany.
Abstract
BACKGROUND: The current TNM system for renal cell carcinoma (RCC) merges perirenal fat invasion (PFI) and renal vein invasion (RVI) as stage pT3a despite limited evidence concerning their prognostic equivalence. In addition, the prognostic value of PFI compared to pT1-pT2 tumors remains controversial. OBJECTIVE: To analyze the prognostic significance of PFI, RVI, and tumor size in pT1-pT3a RCC. DESIGN, SETTING, AND PARTICIPANTS: Data for 7384 pT1a-pT3a RCC patients were pooled from 12 centers. Patients were grouped according to stages and PFI/RVI presence as follows: pT1-2N0M0 (n=6137; 83.1%), pT3aN0M0 + PFI (n=1036; 14%), and pT3aN0M0 (RVI ± PFI; n=211; 2.9%). INTERVENTION: Radical nephrectomy or nephron-sparing surgery (NSS) (1992-2010). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cancer-specific survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional-hazards regression models, as well as sensitivity and discrimination analyses, were used to evaluate the impact of clinicopathologic parameters on cancer-specific mortality (CSM). RESULTS AND LIMITATIONS: Compared to stage pT1-2, patients with stage pT3a RCC were significantly more often male (59.4% vs 53.1%) and older (64.9 vs 62.1 yr), more often had clear cell RCC (85.2% vs 77.7%), Fuhrman grade 3-4 (29.4% vs 13.4%), and tumor size >7 cm (39.1% vs 13%), and underwent NSS less often (7.5% vs 36.6%; all p<0.001). According to multivariate analysis, CSM was significantly higher for the PFI and RVI ± PFI groups compared to pT1-2 patients (hazard ratio [HR] 1.94 and 2.12, respectively; p<0.001), whereas patients with PFI only and RVI ± PFI did not differ (HR 1.17; p=0.316). Tumor size instead enhanced CSM by 7% per cm in stage pT3a (HR 1.07; p<0.001) with a 7 cm cutoff yielding the highest prediction accuracy. CONCLUSIONS: Since the prognostic impact of PFI and RVI on CSM seems to be comparable, merging both as stage pT3a RCC might be justified. Enhanced prognostic discrimination of stage pT3a RCC appears to be possible by applying a tumor size cutoff of 7 cm within an alternative staging system. PATIENT SUMMARY: Prognosis prediction for patients with localized renal cell carcinoma up to stage pT3a can be enhanced by including tumor size with a cutoff of 7 cm as an additional parameter in the TNM classification system.
BACKGROUND: The current TNM system for renal cell carcinoma (RCC) merges perirenal fat invasion (PFI) and renal vein invasion (RVI) as stage pT3a despite limited evidence concerning their prognostic equivalence. In addition, the prognostic value of PFI compared to pT1-pT2 tumors remains controversial. OBJECTIVE: To analyze the prognostic significance of PFI, RVI, and tumor size in pT1-pT3a RCC. DESIGN, SETTING, AND PARTICIPANTS: Data for 7384 pT1a-pT3a RCC patients were pooled from 12 centers. Patients were grouped according to stages and PFI/RVI presence as follows: pT1-2N0M0 (n=6137; 83.1%), pT3aN0M0 + PFI (n=1036; 14%), and pT3aN0M0 (RVI ± PFI; n=211; 2.9%). INTERVENTION: Radical nephrectomy or nephron-sparing surgery (NSS) (1992-2010). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cancer-specific survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional-hazards regression models, as well as sensitivity and discrimination analyses, were used to evaluate the impact of clinicopathologic parameters on cancer-specific mortality (CSM). RESULTS AND LIMITATIONS: Compared to stage pT1-2, patients with stage pT3a RCC were significantly more often male (59.4% vs 53.1%) and older (64.9 vs 62.1 yr), more often had clear cell RCC (85.2% vs 77.7%), Fuhrman grade 3-4 (29.4% vs 13.4%), and tumor size >7 cm (39.1% vs 13%), and underwent NSS less often (7.5% vs 36.6%; all p<0.001). According to multivariate analysis, CSM was significantly higher for the PFI and RVI ± PFI groups compared to pT1-2 patients (hazard ratio [HR] 1.94 and 2.12, respectively; p<0.001), whereas patients with PFI only and RVI ± PFI did not differ (HR 1.17; p=0.316). Tumor size instead enhanced CSM by 7% per cm in stage pT3a (HR 1.07; p<0.001) with a 7 cm cutoff yielding the highest prediction accuracy. CONCLUSIONS: Since the prognostic impact of PFI and RVI on CSM seems to be comparable, merging both as stage pT3a RCC might be justified. Enhanced prognostic discrimination of stage pT3a RCC appears to be possible by applying a tumor size cutoff of 7 cm within an alternative staging system. PATIENT SUMMARY: Prognosis prediction for patients with localized renal cell carcinoma up to stage pT3a can be enhanced by including tumor size with a cutoff of 7 cm as an additional parameter in the TNM classification system.
Authors: Thu Tran; Chandru P Sundaram; Clinton D Bahler; John N Eble; David J Grignon; M Francesca Monn; Novae B Simper; Liang Cheng Journal: J Cancer Date: 2015-07-02 Impact factor: 4.207