Significant increase of synchronous disease in first-line metastatic colorectal cancer trials: Results of a systematic review.
Although synchronous and metachronous metastases are considered as separate entities of metastatic colorectal cancer (mCRC) with different outcomes, its proportion is reported infrequently. We compared inclusion rates and survival of synchronous versus metachronous mCRC in different types of studies investigating initial systemic therapy or surgical treatment of mCRC.



We searched PubMed and EMBASE (January 2004 - February 2016) for mCRC studies investigating first-line systemic therapy or surgical treatment of mCRC including information on synchronous versus metachronous metastases. Outcomes were the proportion of synchronous mCRC, and estimated median overall survival (OS) of the total study population. Spearman analysis (rs) was used to study correlations between outcomes and median year of study enrolment.



We included 46 articles, reporting data from 23 phase 3 randomised controlled trials (RCTs), twenty cohort and three population-based studies (total: 25,941 patients). Seventeen different definitions for synchronous mCRC were identified. In systemic therapy RCTs, we observed an increased proportion of synchronous mCRC during recent years (rs.77, p < .001). In these trials, estimated median OS slightly improved over time (rs.48, p = .03). No significant inclusion or survival trends were observed in included cohort and population-based studies.



In recent years, the proportion of patients with synchronous compared with metachronous mCRC enrolled in first-line systemic therapy RCTs increased. Estimated median OS of the total study population in these RCTs slightly increased over time. Many different definitions of synchronous disease were used. Uniform definitions and consistent reporting of the proportion of synchronous versus metachronous metastases could improve cross-study comparisons and interpretation of reported data in all mCRC studies.
Department of Medical Oncology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
Kaitlyn K H
KK
Goey
Department of Surgery, Radboud University Medical Center, Geert-Grooteplein-Zuid, 6500 HB Nijmegen, The Netherlands.
Jorine
J
't Lam-Boer
Department of Surgery, Radboud University Medical Center, Geert-Grooteplein-Zuid, 6500 HB Nijmegen, The Netherlands.
Johannes H W
JH
de Wilt
Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Cornelis J A
CJ
Punt
Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Martijn G H
MG
van Oijen
Department of Medical Oncology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: m.koopman-6@umcutrecht.nl.
Miriam
M
Koopman
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003082:Colectomy; D015179:Colorectal Neoplasms / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary / Q000628:therapy*; D059146:Metastasectomy; D009362:Neoplasm Metastasis; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate
Colorectal cancer; Metachronous metastases; Metastasis; Synchronous metastases; Systematic review