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Metastatic papillary renal cell carcinoma in the era of targeted therapy: a retrospective study from three European academic centres
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. (Magnus Lindskog)
Deparment of Urology, Ludwig-Maximilians University, Munich Germany.
Deparment of Urology, Ludwig-Maximilians University, Munich Germany.
Department of Oncology-Pathology, Karolinska Institute, Sweden.
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2019 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 58, no 3, p. 306-312Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Metastatic papillary renal cell carcinoma (mPRCC) is understudied. The disease is often aggressive and specific treatment options are lacking.

PATIENTS AND METHODS: mPRCC patients (n = 86) referred to three academic centres in Sweden and Germany in the years 2005-2015 were retrospectively identified from medical records. Statistical analyses included Kaplan-Meier curves and calculation of Cox proportional hazards, generating hazard ratios with 95% confidence intervals. The aim of the study was to evaluate overall survival (OS) of mPRCC patients treated outside of clinical trials in the era of targeted agents (TA) and to identify clinically useful prognostic factors.

RESULTS: Median OS of all mPRCC patients was 11.2 months. TA were used in 77% of the patients and associated with younger age and better Eastern Cooperative Oncology Group performance status (PS). Brain metastases were common (28%). Patients with synchronous or metachronous metastases had similar OS. Variables independently associated with risk of death included age ≥60 years, worse PS and ≥3 metastatic sites. The MSKCC criteria did not provide additional prognostic information. A subgroup analysis of TA-treated patients revealed an association of lymph node metastasis with risk of death in addition to the other prognostic factors.

CONCLUSION: OS in mPRCC remained short in the era of targeted agents. Age, PS, and number of metastatic sites provided independent prognostic information.

Place, publisher, year, edition, pages
2019. Vol. 58, no 3, p. 306-312
Keywords [en]
metastatic, mRCC, non-clear cell, papillary, survival
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
URN: urn:nbn:se:uu:diva-381855DOI: 10.1080/0284186X.2018.1537505ISI: 000462947900007PubMedID: 30507262OAI: oai:DiVA.org:uu-381855DiVA, id: diva2:1305046
Available from: 2019-04-15 Created: 2019-04-15 Last updated: 2019-08-20Bibliographically approved
In thesis
1. Treatment selection in metastatic renal cell carcinoma: Towards an individualised approach
Open this publication in new window or tab >>Treatment selection in metastatic renal cell carcinoma: Towards an individualised approach
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Renal cell carcinoma (RCC), a common malignancy worldwide, affects 1200 new patients yearly in Sweden. Metastatic RCC (mRCC) develops in one in three and is commonly incurable. Clear cell histology dominates followed by papillary histology. The mainstay of mRCC treatment is targeted agents (TA) against aberrantly signalling pro-angiogenic tyrosine kinase receptors, and recently also immune checkpoint inhibitors. Local metastatic therapy with stereotactic radiotherapy (SRT) or surgical metastasectomy may be considered for oligometastatic disease.

The aims of this thesis were (1) to identify clinically relevant factors useful for prognostication in real-world patients with mRCC treated in the TA era, (2) to deepen the understanding of papillary mRCC, and (3) to evaluate local metastatic therapy in mRCC. The papers of this thesis were based on retrospective data from regional databases or patient records from 2005 and onwards to reflect the contemporary therapeutic landscape.

Paper I was a single-centre study analysing inflammatory blood and clinical parameters in relation to overall survival (OS) in mRCC (n=84). Median OS (mOS) was 20 months. Hypoalbuminemia was a negative prognostic factor (HR 2.7), independently of patient performance status (PS) or Memorial Sloan Kettering Cancer Center risk criteria.

Paper II included solely patients with papillary mRCC (n=86) treated at three centres. mOS was 11 months. Age ≥60 years (HR 2.2), ≥3 metastatic sites (HR 2.7), and Eastern Cooperative Oncology Group (ECOG) PS ≥2 vs 1 (HR 3.0) were independently associated with worse OS.

Paper III included mRCC patients treated with local metastatic therapy (n=117). Survival was similar irrespective of SRT or surgical metastasectomy with a mOS of 51 months. Treatment with TA in close proximity to local therapy was well tolerated. ECOG PS 1 vs 0 (HR 2.9), intracranial treatment (HR 1.8), and watchful waiting ≥18 months prior to treatment (HR 0.3) were independently prognostic.  

Paper IV was a follow-up of patients with ccRCC brain metastases treated with single fraction gamma knife radiosurgery (sf-GKRS) at three European centres (n=43). 1- and 3-year local control rates were 97% and 90%, and mOS was 16 months. Hypoalbuminemia (HR=5.3), corticosteroids prior to sf-GKRS (HR=5.8), and Karnofsky PS <80% (HR=9.1) were independently associated with worse OS, whereas previously described prognostic scores were not. Adverse radiation effects (ARE) were uncommon and associated with large target volumes and pre-treatment oedema.

In conclusion, this thesis identifies several factors potentially useful for prognostication in mRCC, and indicates the usefulness of local metastatic therapy, in particular SRT, in selected patients. The results should be validated prospectively.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. p. 88
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1590
Keywords
rcc, renal cell carcinoma, kidney cancer, stereotactic radiotherapy, srt, stereotactic body radiotherapy, sbrt, gamma knife radiosurgery, gkrs, stereotactic radiosurgery, srs, radiotherapy, overall survival, prognostic factor, papillary
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:uu:diva-390138 (URN)978-91-513-0724-4 (ISBN)
Public defence
2019-10-07, Rudbeckssalen, Rudbecklaboratoriet, Uppsala, 13:00 (English)
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Supervisors
Available from: 2019-09-16 Created: 2019-08-20 Last updated: 2019-10-15Bibliographically approved

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