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PLoS One. 2017 Sep 21;12(9):e0184173. doi: 10.1371/journal.pone.0184173. eCollection 2017.

Outcome of papillary versus clear cell renal cell carcinoma varies significantly in non-metastatic disease.

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Department of Urology, Mannheim Medical Center, University of Heidelberg, Mannheim, Germany.
Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany.
Department of Urology, Medical University of Graz, Graz, Austria.
Department of Urology, University Medical Center, University of Mainz, Mainz, Germany.
Department of Urology, Carl-Thiem-Klinikum Cottbus, Cottbus, Germany.
Department of Urology, University of Muenster Medical Center, Muenster, Germany.
Department of Urology, Hospital Clinic, University of Barcelona, Barcelona, Spain.
Unit of Urology and Division of Experimental Oncology, Urological Research Institute (URI), San Raffaele Scientific Institute, University Vita-Salute, Milan, Italy.
Department of Urology, Medical University of Vienna, Vienna, Austria.
Department of Urology, San Pio da Pietrelcina Hospital, Vasto, Italy.
Department of Urology, St. Elisabeth-Hospital Straubing, Straubing, Germany.
Department of Urology, Ludwig-Maximilians-University (LMU), Munich, Germany.


Renal cell carcinoma (RCC) comprises a heterogenous group of tumors. Traditionally, papillary RCC (pRCC) is associated with a favorable outcome compared to clear cell RCC (ccRCC), while other series report equivalent or worse prognosis. In this paper we comparatively evaluate outcome of pRCC versus ccRCC in two large multi-institutional databases (cohort study), including distribution of pRCC subtypes 1 and 2. Retrospective data of 1,943 surgically treated pRCC patients from 17 European/ North American centers between 1984-2015 were compared to 5,600 ccRCC patients from a database comprising 11 European/ North American centers (1984-2011). Median follow-up was 64.6 months. Differences between pRCC, subtypes, and ccRCC were compared with t-tests, Chi^2-tests, and exact Fisher tests. Cancer-specific mortality was analyzed with cumulative incidence curves and Cox cause-specific hazard models. The robustness of our results was examined with sensitivity analyses. We present that cancer-specific mortality rates and variables as stage, lymph node, and distant metastasis differ significantly between groups. Furthermore, we demonstrate that patients with non-metastatic pRCC had a significantly better cancer-specific mortality (HR 0.76, p = 0.007), when compared to ccRCC. Additionally, pRCC type 2 versus ccRCC exhibited no difference in cancer-specific mortality (HR 0.9, p = 0.722), whereas pRCC type 1 versus ccRCC displayed a risk of death reduced by 69% (p = 0.044). Taken together, outcome of pRCC versus ccRCC varies significantly in non-metastatic disease. Furthermore, pRCC type 2 exhibited no difference in cancer-specific mortality, whereas pRCC type 1 displayed a significantly reduced risk of death. Consequently, there is urgent need to respect histopathological entities and their subtypes, when assigning follow-up or targeted therapy to RCC patients.

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