Synchronous Versus Metachronous Metastatic Disease: Impact of Time to Metastasis on Patient Outcome-Results from the International Metastatic Renal Cell Carcinoma Database Consortium.
Advanced kidney cancer
International Metastatic Renal Cell Carcinoma Database Consortium
Metachronous
Metastatic renal cell carcinoma
Renal cell carcinoma
Retrospective
Synchronous
Journal
European urology oncology
ISSN: 2588-9311
Titre abrégé: Eur Urol Oncol
Pays: Netherlands
ID NLM: 101724904
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
01
11
2019
revised:
23
12
2019
accepted:
14
01
2020
pubmed:
11
2
2020
medline:
1
6
2021
entrez:
11
2
2020
Statut:
ppublish
Résumé
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.
Sections du résumé
BACKGROUND
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.
OBJECTIVE
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]).
DESIGN, SETTING, AND PARTICIPANTS
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).
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
OS and TFF were assessed using Kaplan-Meier curves. Cox multivariable regressions analyses (MVAs) were adjusted for baseline factors.
RESULTS AND LIMITATIONS
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.
CONCLUSIONS
Timing of metastases after initial RCC diagnosis may impact the outcomes from targeted therapy in mRCC.
PATIENT SUMMARY
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.
Identifiants
pubmed: 32037304
pii: S2588-9311(20)30008-0
doi: 10.1016/j.euo.2020.01.001
pii:
doi:
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
530-539Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.