Platinum Priority – Kidney CancerEditorial by Matthew D. Galsky on pp. 1093–1094 of this issueSurvival Outcome and Treatment Response of Patients with Late Relapse from Renal Cell Carcinoma in the Era of Targeted Therapy☆
Introduction
More than two-thirds of renal cell carcinoma (RCC) patients are diagnosed with localized disease [1]. However, up to 30% of these patients will ultimately develop metastatic RCC (mRCC) [2], [3]. Using the criteria of adjuvant clinical trials in RCC, a recent retrospective study of primary localized RCC patients who were at high risk for disease recurrence found the median time to disease recurrence between 1.0 and 1.3 yr [3]. Consequently, it is common clinical practice to stop follow-up visits for patients at low risk and extend the periods for follow-up visits for patients with intermediate and high risk after a disease-free interval of approximately 5 yr [2], [4]. However, disease relapse can virtually take place at any time even after periods >5 yr.
Disease recurrence after a disease-free interval of numerous years is commonly characterized by uncertainty for both physicians and patients. Although risk features generally associated with the risk of disease recurrence and late recurrence in particular have been intensively studied [2], [3], [5], there is currently no robust characterization of treatment response and survival outcome after late recurrence. The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk model provides information to stratify patients for clinical trials and for patient counseling to prognosticate overall survival (OS) [6], [7]. Nonetheless, risk models like the IMDC are not sufficient to take every circumstance into consideration that may be of additional importance for patients’ individual outcome.
The aim of the current study was to characterize the treatment response and survival of patients who were diagnosed with metastatic disease from RCC after a disease-free interval >5 yr. The current study did not aim to develop a new prognostication tool. It was the ultimate goal to provide clinical information on this unique subset of mRCC patients. The current study is a project of the IMDC, a collaboration of 20 academic centers.
Section snippets
Study populations
The IMDC database includes centers from North America (Canada, United States), Europe (Denmark, Greece), and Asia (Singapore, Japan, South Korea). Data were collected from August 15, 2008, until February 1, 2013. At the time of analysis, the database contained data on 2754 patients who had received first-line targeted therapy between 2003 and 2013. Relapse from RCC was defined as a diagnosis of recurrent metastatic disease >3 mo after nephrectomy for localized disease based on criteria that
Patient and tumor characteristics
The study cohort was composed of 1210 patients who developed metastatic disease after a disease-free interval > 3 mo. Disease relapse was observed in 897 patients (74%) before 5 yr and in 315 patients (26%) after 5 yr. Overall, 692 patients (56.9%) had died after a median follow-up of 18.5 mo (25th–75th percentile: 9.5–33.1 mo); 1010 (84.0%) had discontinued their initial targeted therapy. The median time to recurrence was 15.3 mo (25th–75th percentile: 7.4–31.9) in ERs and 102.1 mo (25th–75th
Discussion
The current study shows that a quarter of patients treated with targeted therapies and metachronous RCC metastases have disease recurrence after a period >5 yr. The proportion of patients with late recurrence is substantial among the patients treated with targeted therapies, and consequently, physicians should be informed about treatment response and survival outcome of these patients. The current study shows a better response to first-line targeted therapies, a longer PFS, and better OS in LRs
Conclusions
A substantial number of mRCC patients relapse >5 yr after initial nephrectomy, and these patients have more favorable prognostic characteristics. LRs have better treatment response, PFS, and OS when treated with targeted therapy because of more favorable prognostic features. This knowledge is important when informing patients about their prognosis after they have developed a late disease relapse from RCC and may warrant longer term surveillance beyond 5 yr in patients with localized disease.
References (15)
- et al.
Age-adjusted incidence, mortality, and survival rates of stage-specific renal cell carcinoma in North America: a trend analysis
Eur Urol
(2011) - et al.
Postoperative surveillance protocol for patients with localized and locally advanced renal cell carcinoma based on a validated prognostic nomogram and risk group stratification system
J Urol
(2005) - et al.
EAU guidelines on renal cell carcinoma: the 2010 update
Eur Urol
(2010) - et al.
Features associated with recurrence beyond 5 years after nephrectomy and nephron-sparing surgery for renal cell carcinoma: development and internal validation of a risk model (PRELANE score) to predict late recurrence based on a large multicenter database (CORONA/SATURN project)
Eur Urol
(2013) - et al.
New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)
Eur J Cancer
(2009) - et al.
Young age is an independent prognostic factor for survival of sporadic renal cell carcinoma
J Urol
(2004) - et al.
Prediction of progression after radical nephrectomy for patients with clear cell renal cell carcinoma: a stratification tool for prospective clinical trials
Cancer
(2003)
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