Nils Kroeger1, Toni K Choueiri2, Jae-Lyn Lee3, Georg A Bjarnason4, Jennifer J Knox5, Mary J MacKenzie6, Lori Wood7, Sandy Srinivas8, Ulka N Vaishamayan9, Sun-Young Rha10, Sumanta K Pal11, Takeshi Yuasa12, Frede Donskov13, Neeraj Agarwal14, Min-Han Tan15, Aristotelis Bamias16, Christian K Kollmannsberger17, Scott A North18, Brian I Rini19, Daniel Y C Heng20. 1. University of Calgary, Tom Baker Cancer Center, Calgary, AB, Canada; University Medicine Greifswald, Department of Urology, Greifswald, Germany. 2. Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. 3. University of Ulsan College of Medicine, Asan, South Korea. 4. Sunnybrook Odette Cancer Centre, Toronto, ON, Canada. 5. Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada. 6. London Health Sciences Center, London, ON, Canada. 7. Queen Elizabeth II Health Sciences Center, Halifax, NS, Canada. 8. Stanford Cancer Institute, Stanford University, School of Medicine, Stanford, CA, USA. 9. Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA. 10. Yonsei Cancer Centre, Yonsei University College of Medicine, Seoul, South Korea. 11. Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. 12. Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. 13. Department of Oncology, Aarhus University Hospital, Aarhus, Denmark. 14. University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA. 15. Department of Medical Oncology, National Cancer Centre and Institute of Bioengineering and Nanotechnology, Singapore. 16. Department of Clinical Therapeutics, University of Athens, Athens, Greece. 17. Vancouver Cancer Center, British Columbia Cancer Agency, Vancouver, BC, Canada. 18. Cross Cancer Center, University of Alberta, Edmonton, AB, Canada. 19. Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA. 20. University of Calgary, Tom Baker Cancer Center, Calgary, AB, Canada. Electronic address: daniel.heng@albertahealthservices.ca.
Abstract
BACKGROUND: A subset of primarily localized renal cell carcinoma (RCC) patients will experience disease recurrence ≥5 yr after initial nephrectomy. OBJECTIVE: To characterize the clinical outcome of patients with late recurrence beyond 5 yr. DESIGN, SETTING, AND PARTICIPANTS: Patients with metastatic RCC (mRCC) treated with targeted therapy were retrospectively characterized according to time to relapse. Relapse was defined as the diagnosis of recurrent metastatic disease >3 mo after initial curative-intent nephrectomy. Patients with synchronous metastatic disease at presentation were excluded. Patients were classified as early relapsers (ERs) if they recurred within 5 yr; late relapsers (LRs) recurred after 5 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Demographics were compared with the Student t test, the chi-square test, or the Fisher exact test. The survival time was estimated with the Kaplan-Meier method, and associations with survival outcome were assessed with univariable and multivariable Cox regression analyses. RESULTS AND LIMITATIONS: Among 1210 mRCC patients treated with targeted therapy after surgery for localized disease, 897 (74%) relapsed within the first 5 yr and 313 (26%) (range: 5-35 yr) after 5 yr. LRs presented with younger age (p<0.0001), fewer with sarcomatoid features (p<0.0001), more clear cell histology (p=0.001), and lower Fuhrman grade (p<0.0001). Overall objective response rates to targeted therapy were better in LRs versus ERs (31.8% vs 26.5%; p=0.004). LRs had significantly longer progression-free survival (10.7 mo vs 8.5 mo; p=0.005) and overall survival (OS; 34.0 mo vs 27.4 mo; p=0.004). The study is limited by its retrospective design, noncentralized imaging and pathology review, missing information on metastatectomy, and nonstandardized follow-up protocols. CONCLUSIONS: A quarter of patients who eventually developed metastatic disease and were treated with targeted therapy relapsed over 5 yr from initial nephrectomy. LRs have more favorable prognostic features and consequently better treatment response and OS.
BACKGROUND: A subset of primarily localized renal cell carcinoma (RCC) patients will experience disease recurrence ≥5 yr after initial nephrectomy. OBJECTIVE: To characterize the clinical outcome of patients with late recurrence beyond 5 yr. DESIGN, SETTING, AND PARTICIPANTS: Patients with metastatic RCC (mRCC) treated with targeted therapy were retrospectively characterized according to time to relapse. Relapse was defined as the diagnosis of recurrent metastatic disease >3 mo after initial curative-intent nephrectomy. Patients with synchronous metastatic disease at presentation were excluded. Patients were classified as early relapsers (ERs) if they recurred within 5 yr; late relapsers (LRs) recurred after 5 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Demographics were compared with the Student t test, the chi-square test, or the Fisher exact test. The survival time was estimated with the Kaplan-Meier method, and associations with survival outcome were assessed with univariable and multivariable Cox regression analyses. RESULTS AND LIMITATIONS: Among 1210 mRCC patients treated with targeted therapy after surgery for localized disease, 897 (74%) relapsed within the first 5 yr and 313 (26%) (range: 5-35 yr) after 5 yr. LRs presented with younger age (p<0.0001), fewer with sarcomatoid features (p<0.0001), more clear cell histology (p=0.001), and lower Fuhrman grade (p<0.0001). Overall objective response rates to targeted therapy were better in LRs versus ERs (31.8% vs 26.5%; p=0.004). LRs had significantly longer progression-free survival (10.7 mo vs 8.5 mo; p=0.005) and overall survival (OS; 34.0 mo vs 27.4 mo; p=0.004). The study is limited by its retrospective design, noncentralized imaging and pathology review, missing information on metastatectomy, and nonstandardized follow-up protocols. CONCLUSIONS: A quarter of patients who eventually developed metastatic disease and were treated with targeted therapy relapsed over 5 yr from initial nephrectomy. LRs have more favorable prognostic features and consequently better treatment response and OS.
Authors: Toni K Choueiri; Bernard Escudier; Thomas Powles; Paul N Mainwaring; Brian I Rini; Frede Donskov; Hans Hammers; Thomas E Hutson; Jae-Lyun Lee; Katriina Peltola; Bruce J Roth; Georg A Bjarnason; Lajos Géczi; Bhumsuk Keam; Pablo Maroto; Daniel Y C Heng; Manuela Schmidinger; Philip W Kantoff; Anne Borgman-Hagey; Colin Hessel; Christian Scheffold; Gisela M Schwab; Nizar M Tannir; Robert J Motzer Journal: N Engl J Med Date: 2015-09-25 Impact factor: 91.245
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Authors: Tim J van Oostenbrugge; Stephanie G C Kroeze; J L H Ruud Bosch; Harm H E van Melick Journal: World J Urol Date: 2014-09-02 Impact factor: 4.226