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Pubmed, EMBASE and Cochrane library were searched for prospective studies on metastatic colorectal cancer to conduct a meta\u2010analysis. Inclusion criteria consisted of metastatic disease, systemic treatment with palliative intent and specification of primary tumor location. Data were pooled using a random\u2010effects model. For the population\u2010based data, multivariable Cox models were constructed. The Grambsch\u2010Therneau test was conducted to evaluate the potential time\u2010varying nature of sidedness. Meta\u2010regression incorporating treatment\u2010line as variable was conducted to test the pre\u2010specified hypothesis that the prognostic value of sidedness varies over time. Analysis of 12\u2009885 and 16\u2009160 synchronous metastatic colorectal cancer patients registered in the Netherlands Cancer Registry and SEER database, respectively, indicated a time\u2010varying prognostic value of sidedness (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.01). Thirty\u2010one studies were selected for the meta\u2010analysis (9558 patients for overall survival analysis). Pooled univariable hazard ratio<jats:sub>left\u2010sided\/right\u2010sided<\/jats:sub> for overall survival was 0.71 (95% CI: 0.65\u20100.76) in 1st\u2010line, 0.76 (0.54\u20101.06) in 2nd\u2010line and 1.01 (0.86\u20101.19) in 3rd\u2010line studies. Hazard ratios were significantly influenced by treatment line (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.035). The prognostic value of sidedness of the primary tumor in metastatic colorectal cancer patients treated with palliative systemic therapy decreases over time since diagnosis, suggesting that sidedness may not be a useful stratification factor in late\u2010line trials. This decrease in prognostic value should be taken into account when providing prognostic information to patients.<\/jats:p>","DOI":"10.1002\/ijc.34347","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T12:35:13Z","timestamp":1667910913000},"page":"1360-1369","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Time\u2010varying prognostic value of primary tumor sidedness in metastatic colorectal cancer: A population\u2010based study and meta\u2010analysis"],"prefix":"10.1002","volume":"152","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0639-2426","authenticated-orcid":false,"given":"Dave E. W.","family":"van der Kruijssen","sequence":"first","affiliation":[{"name":"Department of Medical Oncology University Medical Center Utrecht, Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Auke J. S.","family":"van der Kuil","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology University Medical Center Utrecht, Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geraldine R.","family":"Vink","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology University Medical Center Utrecht, Utrecht University  Utrecht The Netherlands"},{"name":"Department of Research and development Netherlands Comprehensive Cancer Organisation (IKNL)  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelis J. A.","family":"Punt","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Julius Center for Health Sciences and Primary Care University Medical Center Utrecht, Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes H. 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