Are We Using the Best Tumor Size Cut-points for Renal Cell Carcinoma Staging?


      To compare the predictive ability for oncologic outcomes among current tumor size cut-points and clinically relevant alternatives to determine which are optimal.


      Patients who underwent radical or partial nephrectomy between 1970 and 2010 for T1-2Nx/N0M0 renal cell carcinoma (RCC) were identified. Associations between tumor size and progression-free survival (PFS) and cancer-specific survival (CSS) were evaluated using Kaplan-Meier analyses and Cox models. Predictive ability was assessed using c-indexes.


      The cohort included 3304 patients with a median age of 63 years (interquartile range 53, 70). Median follow-up among survivors was 9.9 years (interquartile range 6.9, 14.3). There were 536 patients who progressed and 354 who died from RCC. For RCC tumors ≤3.0 cm, 10-year PFS and CSS rates were 93%-95% and 97%-99%, respectively. For tumors >3.0-4.0 cm, PFS and CSS began to decline (91% and 95%, respectively), with further gradual declines in PFS and CSS with increasing tumor size. Plots of hazard ratios for progression and RCC death as a function of tumor size did not reveal major inflection points. Differences in discrimination based on various combinations of tumor-size cut-points for progression or RCC death were small, with c-indexes ranging between 0.691-0.704 and 0.734-0.750, respectively.


      RCC tumors ≤3.0 cm in size are associated with favorable outcomes. Thereafter, risks of progression and RCC death increase gradually with tumor size, with no compelling biological reason to endorse a given cut-point over another.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Urology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Rini B.I.
        • McKiernan J.M.
        • Chang S.S.
        • et al.
        in: Amin M.B. AJCC Cancer Staging Manual. 8th ed. Springer, Chicago2017: 739-748
        • Moch H.
        • Artibani W.
        • Delahunt B.
        • et al.
        Reassessing the current UICC/AJCC TNM staging for renal cell carcinoma.
        Eur Urol. 2009; 56: 636-643
        • Tsui K.H.
        • Shvarts O.
        • Smith R.B.
        • Figlin R.A.
        • deKernion J.B.
        • Belldegrun A.
        Prognostic indicators for renal cell carcinoma: a multivariate analysis of 643 patients using the revised 1997 TNM staging criteria.
        J Urol. 2000; 163 (quiz 1295): 1090-1095
        • Hafez K.S.
        • Fergany A.F.
        • Novick A.C.
        Nephron sparing surgery for localized renal cell carcinoma: impact of tumor size on patient survival, tumor recurrence and TNM staging.
        J Urol. 1999; 162: 1930-1933
        • Frank I.
        • Blute M.L.
        • Leibovich B.C.
        • et al.
        pT2 classification for renal cell carcinoma. Can its accuracy be improved?.
        J Urol. 2005; 173: 380-384
        • Bedke J.
        • Pritsch M.
        • Buse S.
        • et al.
        Prognostic stratification of localized renal cell carcinoma by tumor size.
        J Urol. 2008; 180: 62-67
        • Steiner T.
        • Knels R.
        • Schubert J.
        Prognostic significance of tumour size in patients after tumour nephrectomy for localised renal cell carcinoma.
        Eur Urol. 2004; 46: 327-330
        • Novara G.
        • Ficarra V.
        • Antonelli A.
        • et al.
        Validation of the 2009 TNM version in a large multi-institutional cohort of patients treated for renal cell carcinoma: are further improvements needed?.
        Eur Urol. 2010; 58: 588-595
        • Waalkes S.
        • Becker F.
        • Schrader A.J.
        • et al.
        Is there a need to further subclassify pT2 renal cell cancers as implemented by the revised 7th TNM version?.
        Eur Urol. 2011; 59: 258-263
        • Ficarra V.
        • Prayer-Galetti T.
        • Novara G.
        • et al.
        Tumor-size breakpoint for prognostic stratification of localized renal cell carcinoma.
        Urology. 2004; 63 (discussion 239-240): 235-239
        • Zisman A.
        • Pantuck A.J.
        • Chao D.
        • et al.
        Reevaluation of the 1997 TNM classification for renal cell carcinoma: T1 and T2 cutoff point at 4.5 rather than 7 cm. better correlates with clinical outcome.
        J Urol. 2001; 166: 54-58
        • Elmore J.M.
        • Kadesky K.T.
        • Koeneman K.S.
        • Sagalowsky A.I.
        Reassessment of the 1997 TNM classification system for renal cell carcinoma.
        Cancer. 2003; 98: 2329-2334
        • Bianchi M.
        • Becker A.
        • Trinh Q.D.
        • et al.
        An analysis of patients with T2 renal cell carcinoma (RCC) according to tumour size: a population-based analysis.
        BJU Int. 2013; 111: 1184-1190
        • Klatte T.
        • Patard J.J.
        • Goel R.H.
        • et al.
        Prognostic impact of tumor size on pT2 renal cell carcinoma: an international multicenter experience.
        J Urol. 2007; 178 (discussion 40): 35-40
        • Ficarra V.
        • Guille F.
        • Schips L.
        • et al.
        Proposal for revision of the TNM classification system for renal cell carcinoma.
        Cancer. 2005; 104: 2116-2123
        • Kitagawa Y.
        • Nakashima K.
        • Shima T.
        • et al.
        Clinicopathological outcomes of clinical T1a renal cell carcinoma by tumor size.
        Jpn J Clin Oncol. 2011; 41: 637-641
        • Targonski P.V.
        • Frank W.
        • Stuhldreher D.
        • Guinan P.D.
        Value of tumor size in predicting survival from renal cell carcinoma among tumors, nodes and metastases stage 1 and stage 2 patients.
        J Urol. 1994; 152: 1389-1392
        • Kinouchi T.
        • Saiki S.
        • Meguro N.
        • et al.
        Impact of tumor size on the clinical outcomes of patients with Robson State I renal cell carcinoma.
        Cancer. 1999; 85: 689-695
        • Uzzo R.G.
        • Novick A.C.
        Nephron sparing surgery for renal tumors: indications, techniques and outcomes.
        J Urol. 2001; 166: 6-18
        • Mir M.C.
        • Derweesh I.
        • Porpiglia F.
        • Zargar H.
        • Mottrie A.
        • Autorino R.
        Partial nephrectomy versus radical nephrectomy for clinical T1b and T2 renal tumors: a systematic review and meta-analysis of comparative studies.
        Eur Urol. 2016; 71: 606-617
        • Duffey B.G.
        • Choyke P.L.
        • Glenn G.
        • et al.
        The relationship between renal tumor size and metastases in patients with von Hippel-Lindau disease.
        J Urol. 2004; 172: 63-65
        • Varkarakis I.M.
        • Allaf M.E.
        • Inagaki T.
        • et al.
        Percutaneous radio frequency ablation of renal masses: results at a 2-year mean followup.
        J Urol. 2005; 174 (discussion 460): 456-460
        • Delahunt B.
        • Cheville J.C.
        • Martignoni G.
        • et al.
        The International Society of Urological Pathology (ISUP) grading system for renal cell carcinoma and other prognostic parameters.
        Am J Surg Pathol. 2013; 37: 1490-1504
        • Igarashi T.
        • Tobe T.
        • Nakatsu H.O.
        • et al.
        The impact of a 4 cm. cutoff point for stratification of T1N0M0 renal cell carcinoma after radical nephrectomy.
        J Urol. 2001; 165: 1103-1106
        • Delahunt B.
        • Kittelson J.M.
        • McCredie M.R.
        • Reeve A.E.
        • Stewart J.H.
        • Bilous A.M.
        Prognostic importance of tumor size for localized conventional (clear cell) renal cell carcinoma: assessment of TNM T1 and T2 tumor categories and comparison with other prognostic parameters.
        Cancer. 2002; 94: 658-664
        • Kim S.P.
        • Alt A.L.
        • Weight C.J.
        • et al.
        Independent validation of the 2010 American Joint Committee on Cancer TNM classification for renal cell carcinoma: results from a large, single institution cohort.
        J Urol. 2011; 185: 2035-2039
        • Lau W.K.
        • Cheville J.C.
        • Blute M.L.
        • Weaver A.L.
        • Zincke H.
        Prognostic features of pathologic stage T1 renal cell carcinoma after radical nephrectomy.
        Urology. 2002; 59: 532-537
        • Umbreit E.C.
        • Shimko M.S.
        • Childs M.A.
        • et al.
        Metastatic potential of a renal mass according to original tumour size at presentation.
        BJU Int. 2012; 109 (discussion 194): 190-194
        • Altman D.G.
        • Royston P.
        The cost of dichotomising continuous variables.
        BMJ. 2006; 332: 1080