Synchronous Versus Metachronous Metastatic Disease: Impact of Time to Metastasis on Patient Outcome-Results from the International Metastatic Renal Cell Carcinoma Database Consortium.

Patients with metastatic renal cell carcinoma (mRCC) may present with primary metastases (synchronous disease) or develop metastases during follow-up (metachronous disease). The impact of time to metastasis on patient outcome is poorly characterised.

To characterise overall survival (OS) and time to treatment failure (TTF) based on time to metastasis in mRCC patients treated with targeted therapy (tyrosine kinase inhibitors [TKIs]).

We used the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) to compare synchronous (metastases within ≤3 mo of initial diagnosis of cancer) versus metachronous disease (evaluated by >3-12 mo, >1-2 yr, >2-7 yr, and >7 yr intervals).

OS and TFF were assessed using Kaplan-Meier curves. Cox multivariable regressions analyses (MVAs) were adjusted for baseline factors.

Of 7386 patients with mRCC treated with first-line TKIs, 3906 (53%) and 3480 (47%) had synchronous and metachronous metastasis, respectively. More patients with synchronous versus metachronous disease had higher T stage (T1-2: 19% vs 34%), N1 disease (21% vs 6%), presence of sarcomatoid differentiation (15.8% vs 7.9%), Karnofsky performance status <80 (25.9% vs 15.1%), anaemia (62.5% vs 42.3%), elevated neutrophils (18.9% vs 10.9%), elevated platelets (21.6% vs 11.4%), bone metastases (40.4% vs 29.8%), and IMDC poor risk (40.6% vs 11.3%). Synchronous versus metachronous disease by intervals >3-12 mo, >1-2 yr, >2-7 yr, and >7 yr correlated with poor TTF (5.6 mo vs 7.3, 8.0, 10.8, and 13.3 mo, p <  0.0001) and poor OS (median 16.7 mo vs 23.8, 30.2, 34.8, and 41.7 mo, p <  0.0001). In MVAs, the adjusted hazard ratios (95% confidence intervals) were 1.00 (reference), 0.98 (0.90-1.06), 0.81 (0.73-0.91), 0.74 (0.68-0.81), and 0.60 (0.54-0.67), respectively, for OS (p <  0.0001), and 1.00 (reference), 0.99 (0.92-1.06), 0.98 (0.90-1.07), 0.83 (0.77-0.89), and 0.66 (0.60-0.72), respectively, for TTF (p <  0.0001). Data were collected retrospectively.

Timing of metastases after initial RCC diagnosis may impact the outcomes from targeted therapy in mRCC.

We looked at the impact of the timing of metastatic outbreak on survival outcomes in kidney cancer patients treated with targeted therapy. We found that the longer time to metastatic development was associated with improved outcome.

European urology oncology. 2020 Feb 06 [Epub ahead of print]

Frede Donskov, Wanling Xie, Anders Overby, J Connor Wells, Anna P Fraccon, Cosimo S Sacco, Camillo Porta, Igor Stukalin, Jae-Lyun Lee, Konstantinos Koutsoukos, Takeshi Yuasa, Ian D Davis, Carmel Pezaro, Ravindran Kanesvaran, Georg A Bjarnason, Hao-Wen Sim, Nityam Rathi, Christian K Kollmannsberger, Christina M Canil, Toni K Choueiri, Daniel Y C Heng

Aarhus University Hospital, Aarhus, Denmark. Electronic address: ., Dana-Farber Cancer Institute, Boston, MA, USA., Aarhus University Hospital, Aarhus, Denmark., Tom Baker Cancer Center, Calgary, Canada., Medical Oncology Unit, Ospedale Pederzoli, Peschiera del Garda, Verona, Italy., IRCCS San Matteo University Hospital, Pavia, Italy., Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea., Nation and Kapodistrian University of Athens, Athens, Greece., Cancer Institute Hospital, Tokyo, Japan., Monash University and Eastern Health, Melbourne, Australia., National Cancer Centre Singapore, Singapore., Sonnybrook Odette Cancer Center, Toronto, Canada., Princess Margaret Cancer Centre, Toronto, Canada., Huntsman Cancer Institute, Salt Lake City, UT, USA., British Columbia Cancer Agency, Vancouver, Canada., Ottawa Hospital Cancer Centre, Ottawa, Canada.