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Comparison of Survival Outcomes in Patients with Metastatic Papillary vs. Clear-Cell Renal Cell Carcinoma: A Propensity-Score Analysis - Beyond the Abstract

Papillary renal cell carcinoma subtype (pRCC) is the second most common histological subtype in kidney cancer.1 Although several studies have shown that it is associated with better outcomes than clear cell RCC (ccRCC) in non-metastatic disease,2 conflicting results have been found regarding the setting of metastatic RCC.3,4 Moreover, few data are available on survival outcomes according to histology and treatment modality.5 In consequence, the aim of our study was to compare outcomes of metastatic pRCC vs. ccRCC overall and according to the most common treatment modalities used in this setting of patients, namely cytoreductive nephrectomy (CN) alone, targeted therapy (TT) alone, or in combination with CN.


To address this point, we relied on a population-based database, namely the Surveillance, Epidemiology and End Results (SEER) database, including 6,215 patients with metastatic ccRCC and 585 patients with metastatic pRCC diagnosed between 2006 and 2015. Our statistical methodologies included Kaplan-Meier analyses for survival estimates and multivariable Cox-regression analyses to adjust our results for several demographic and pathologic confounders. Moreover, we relied on propensity-score matching analyses which allowed us to reduce the effect of selection bias.6

Overall, 6,215 (10.1%) ccRCC and 585 (4.6%) pRCC harbored metastatic disease. Interestingly, rates of nodal metastases were two-fold higher in pRCC vs. ccRCC patients (49.7 vs. 23.3%) and African-Americans showed incredibly higher rates of pRCC than ccRCC histological subtype (27 vs. 6.6%). In the overall cohort, median overall survival (OS) and cancer-specific survival (CSS) were shorter in pRCC than ccRCC patients (13 vs. 18 and 12 vs. 18 months, respectively), but after propensity-score matching and multivariable adjustment, no survival differences remained. Finally, survival analyses according to treatment modality demonstrated shorter median OS and CSS in pRCC than ccRCC patients, regardless of treatment received.

Several noteworthy observations may be derived from our study. First, ccRCC histological subtype confirms its aggressiveness, since a higher proportion of ccRCC progresses to metastatic disease, compared to pRCC histology. Second, important baseline differences can be found in the context of metastatic RCC. Specifically, pRCC shows a predilection for African-American ethnicity, and it is associated with incredibly higher rates of nodal metastases compared to ccRCC histology. Finally, survival analyses show that pRCC is an aggressive and unfavorable tumor histology in the presence of metastatic disease since it demonstrates poor OS and CSS overall regardless of treatment received.

In conclusion, our observations indicate that papillary variant represents more prognostically unfavorable tumor histology in the context of metastatic RCC, showing a predilection for nodal spreading and African-American ethnicity. In consequence, further investigations are needed to evaluate the biological rationale behind these noteworthy findings, that may guide future targeted treatment of these patients.

Written by: Giuseppe Rosiello, Carlotta Palumbo, Sophie Knipper, Angela Pecoraro, Stefano Luzzago, Pierre-Antoine St-Hilaire, Zhe Tian, Umberto Capitanio, Francesco Montorsi, Shahrokh F Shariat, Fred Saad, Alberto Briganti, Pierre I Karakiewicz


Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, QC, Canada. ., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, QC, Canada., Department of Urology and Division of Experimental Oncology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.

References:

  1. Störkel, S., J. N. Eble, K. Adlakha, M. Amin, M. L. Blute, D. G. Bostwick, M. Darson, B. Delahunt, and K. Iczkowski. "Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC). Classification of renal cell carcinoma: Workgroup No. 1." Cancer 80, no. 5 (1997): 987-989.
  2. Capitanio, Umberto, Vincent Cloutier, Laurent Zini, Hendrik Isbarn, Claudio Jeldres, Shahrokh F. Shariat, Paul Perrotte et al. "A critical assessment of the prognostic value of clear cell, papillary and chromophobe histological subtypes in renal cell carcinoma: a population‐based study." BJU international 103, no. 11 (2009): 1496-1500.
  3. Patard, Jean-Jacques, Emmanuelle Leray, Nathalie Rioux-Leclercq, Luca Cindolo, Vincenzo Ficarra, Amnon Zisman, Alexandre De La Taille et al. "Prognostic value of histologic subtypes in renal cell carcinoma: a multicenter experience." Journal of Clinical Oncology 23, no. 12 (2005): 2763-2771.
  4. Connor Wells, John, Frede Donskov, Anna P. Fraccon, Felice Pasini, Georg A. Bjarnason, Benoit Beuselinck, Jennifer J. Knox et al. "Characterizing the outcomes of metastatic papillary renal cell carcinoma." Cancer medicine 6, no. 5 (2017): 902-909.
  5. Ravaud, A., S. Oudard, M. De Fromont, C. Chevreau, G. Gravis, S. Zanetta, C. Theodore et al. "First-line treatment with sunitinib for type 1 and type 2 locally advanced or metastatic papillary renal cell carcinoma: a phase II study (SUPAP) by the French Genitourinary Group (GETUG)." Annals of Oncology 26, no. 6 (2015): 1123-1128.
  6. Dell’Oglio, Paolo, Geert De Naeyer, Lyu Xiangjun, Zachary Hamilton, Umberto Capitanio, Francesco Ripa, Francesco Cianflone et al. "The Impact of Surgical Strategy in Robot-assisted Partial Nephrectomy: Is It Beneficial to Treat Anterior Tumours with Transperitoneal Access and Posterior Tumours with Retroperitoneal Access?." European urology oncology (2019).
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