Clinical Outcomes in Patients With Metastatic Papillary Renal-Cell Carcinoma: A Multi-Institutional Study in Japan

Published:August 10, 2018DOI:



      Standard treatments have not been established in metastatic papillary renal-cell carcinoma (PRCC). We aimed to investigate treatment outcomes in patients with mPRCC.

      Patients and Methods

      This study included 51 patients who were diagnosed with PRCC at 14 institutions. Pathologic slides were reviewed by pathologists. The associations between clinical factors and overall survival (OS) were analyzed.


      Final pathologic diagnoses could be determined in 50 patients. Thirty-five tumors were diagnosed as PRCC (type 2 PRCC, 91.4%), and 15 were diagnosed as other histologic types. Targeted therapies (TTs) were provided to 25 mPRCC patients. Patients treated with TT survived significantly longer than those treated before the era of TT (median OS, 22.5 vs. 6.3 months; P = .0035). Median OS of patients who experienced stable disease for ≥ 9 months using single TT was 43.1 months. Patients treated with a tyrosine kinase inhibitor (TKI) as first-line TT survived longer after TT initiation than those treated with an mTOR inhibitor (median, 22.4 vs. 11.7 months; P = .2684). Patients treated with TKIs in both first- and second-line settings had significantly better survival after TT initiation than those treated with a TKI in one therapy line and an mTOR inhibitor in the other (31.4 vs. 12.9 months, P = .0172). Patients treated with a TKI as second-line TT survived significantly longer after second-line TT initiation than did those treated with an mTOR inhibitor (16.2 vs. 7.4 months, P = .0016).


      Prognoses of patients with mPRCC were improved by TT, and TKIs appeared to be the treatment of choice in both the first- and second-line settings.


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        • Ronnen E.A.
        • Kondagunta G.V.
        • Ishill N.
        • et al.
        Treatment outcome for metastatic papillary renal cell carcinoma patients.
        Cancer. 2006; 107: 2617-2621
        • Margulis V.
        • Tamboli P.
        • Matin S.F.
        • Swanson D.A.
        • Wood C.G.
        Analysis of clinicopathologic predictors of oncologic outcome provides insight into the natural history of surgically managed papillary renal cell carcinoma.
        Cancer. 2008; 112: 1480-1488
        • Simone G.
        • Tuderti G.
        • Ferriero M.
        • et al.
        Papillary type 2 versus clear cell renal cell carcinoma: survival outcomes.
        Eur J Surg Oncol. 2016; 42: 1744-1750
        • Moch H.
        • Humphrey P.A.
        • Ulbright T.M.
        • Reuter V.E.
        WHO classification of tumours of the urinary system and male genital organs. 4th ed. IARC Press, Lyon, France2016
        • Amin M.B.
        • Amin M.B.
        • Tamboli P.
        • et al.
        Prognostic impact of histologic subtyping of adult renal epithelial neoplasms: an experience of 405 cases.
        Am J Surg Pathol. 2002; 26: 281-291
        • Wahlgren T.
        • Harmenberg U.
        • Sandström P.
        • et al.
        Treatment and overall survival in renal cell carcinoma: a Swedish population-based study (2000-2008).
        Br J Cancer. 2013; 108: 1541-1549
        • Calvo E.
        • Schmidinger M.
        • Heng D.Y.
        • Grünwald V.
        • Escudier B.
        Improvement in survival end points of patients with metastatic renal cell carcinoma through sequential targeted therapy.
        Cancer Treat Rev. 2016; 50: 109-117
        • Hudes G.
        • Carducci M.
        • Tomczak P.
        • et al.
        Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma.
        N Engl J Med. 2007; 356: 2271-2281
        • Choueiri T.K.
        • Plantade A.
        • Elson P.
        • et al.
        Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma.
        J Clin Oncol. 2008; 26: 127-131
        • Gore M.E.
        • Szczylik C.
        • Porta C.
        • et al.
        Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial.
        Lancet Oncol. 2009; 10: 757-763
        • Dutcher J.P.
        • de Souza P.
        • McDermott D.
        • et al.
        Effect of temsirolimus versus interferon-alpha on outcome of patients with advanced renal cell carcinoma of different tumor histologies.
        Med Oncol. 2009; 26: 202-209
        • Voss M.H.
        • Bastos D.A.
        • Karlo C.A.
        • et al.
        Treatment outcome with mTOR inhibitors for metastatic renal cell carcinoma with nonclear and sarcomatoid histologies.
        Ann Oncol. 2014; 25: 663-668
        • Tannir N.M.
        • Plimack E.
        • Ng C.
        • et al.
        A phase 2 trial of sunitinib in patients with advanced non–clear cell renal cell carcinoma.
        Eur Urol. 2012; 62: 1013-1019
        • Lee J.L.
        • Ahn J.H.
        • Lim H.Y.
        • et al.
        Multicenter phase II study of sunitinib in patients with non–clear cell renal cell carcinoma.
        Ann Oncol. 2012; 23: 2108-2114
        • Molina A.M.
        • Feldman D.R.
        • Ginsberg M.S.
        • et al.
        Phase II trial of sunitinib in patients with metastatic non–clear cell renal cell carcinoma.
        Invest New Drugs. 2012; 30: 335-340
        • Tannir N.M.
        • Jonasch E.
        • Albiges L.
        • et al.
        Everolimus versus sunitinib prospective evaluation in metastatic non–clear cell renal cell carcinoma (ESPN): a randomized multicenter phase 2 trial.
        Eur Urol. 2016; 69: 866-874
        • Armstrong A.J.
        • Halabi S.
        • Eisen T.
        • et al.
        Everolimus versus sunitinib for patients with metastatic non–clear cell renal cell carcinoma (ASPEN): a multicentre, open-label, randomised phase 2 trial.
        Lancet Oncol. 2016; 17: 378-388
        • Ravaud A.
        • Oudard S.
        • De Fromont M.
        • 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).
        Ann Oncol. 2015; 26: 1123-1128
        • Escudier B.
        • Molinie V.
        • Bracarda S.
        • et al.
        Open-label phase 2 trial of first-line everolimus monotherapy in patients with papillary metastatic renal cell carcinoma: RAPTOR final analysis.
        Eur J Cancer. 2016; 69: 226-235
        • Linehan W.M.
        • Rathmell W.K.
        Kidney cancer.
        Urol Oncol. 2012; 30: 948-951
        • Linehan W.M.
        • Srinivasan R.
        • Garcia J.A.
        Non–clear cell renal cancer: disease-based management and opportunities for targeted therapeutic approaches.
        Semin Oncol. 2013; 40: 511-520
        • Ito K.
        • Asano T.
        • Yoshii H.
        • Satoh A.
        • Sumitomo M.
        • Hayakawa M.
        Impact of thrombocytosis and C-reactive protein elevation on the prognosis for patients with renal cell carcinoma.
        Int J Urol. 2006; 13: 1365-1370
        • Motzer R.J.
        • Bacik J.
        • Murphy B.A.
        • Russo P.
        • Mazumdar M.
        Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma.
        J Clin Oncol. 2002; 20: 289-296
        • Ito K.
        • Yoshii H.
        • Sato A.
        • et al.
        Impact of postoperative C-reactive protein level on recurrence and prognosis in patients with N0M0 clear cell renal cell carcinoma.
        J Urol. 2011; 186: 430-435
        • Buti S.
        • Bersanelli M.
        • Maines F.
        • et al.
        First-line pazopanib in non–clear-cell renal carcinoma: the Italian retrospective multicenter PANORAMA study.
        Clin Genitourin Cancer. 2017; 15: e609-e614
        • Jung K.S.
        • Lee S.J.
        • Park S.H.
        • et al.
        Pazopanib for the treatment of non–clear cell renal cell carcinoma. A single-arm, open-label, multicenter, phase II study.
        Cancer Res Treat. 2018; 50: 488-494
        • Naito S.
        • Kinoshita H.
        • Kondo T.
        • et al.
        Prognostic factors of patients with metastatic renal cell carcinoma with removed metastases: a multicenter study of 556 patients.
        Urology. 2013; 82: 846-851