Department of Hepato-Gastroenterology, University Hospital La Cavale Blanche, Brest, France.
Digestive Cancer Registry of Burgundy, Dijon, France.
JAMA Netw Open. 2022 Oct 3;5(10):e2236666. doi: 10.1001/jamanetworkopen.2022.36666.
Although treatment and prognosis of synchronous liver metastases from colorectal cancer are relatively well known, a comparative description of the incidence, epidemiological features, and outcomes of synchronous and metachronous liver metastases is lacking. The difference in prognosis between patients with synchronous and metachronous liver metastases is controversial.
To investigate temporal patterns in the incidence and outcomes of synchronous vs metachronous liver metastases from colorectal cancer.
DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study used information from a French regional digestive cancer registry accounting for 1 082 000 inhabitants. A total of 26 813 patients with a diagnosis of incident colorectal adenocarcinoma diagnosed between January 1, 1976, and December 31, 2018, were included. Data were analyzed from February 7 to May 20, 2022.
Age-standardized incidence was calculated. Univariate and multivariate net survival analyses were performed.
Of 26 813 patients with colorectal cancer (15 032 men [56.1%]; median [IQR] age, 73 [64-81] years), 4546 (17.0%) presented with synchronous liver metastases. The incidence rate of synchronous liver metastases was 6.9 per 100 000 inhabitants in men and 3.4 per 100 000 inhabitants in women, with no significant variation since 2000. The 5-year cumulative incidence of metachronous liver metastases decreased from 18.6% (95% CI, 14.9%-22.2%) during the 1976 to 1980 period to 10.0% (95% CI, 8.8%-11.2%) during the 2006 to 2011 period. Cancer stage at diagnosis was the strongest risk factor for liver metastases; compared with patients diagnosed with stage II cancer, patients with stage III cancer had a 2-fold increase in risk (subdistribution hazard ratio, 2.42; 95% CI, 2.08-2.82) for up to 5 years. Net survival at 1 year was 41.8% for synchronous liver metastases and 49.9% for metachronous metastases, and net survival at 5 years was 6.2% for synchronous liver metastases and 13.2% for metachronous metastases. Between the first (1976-1980) and last (2011-2016) periods, the adjusted ratio of death after synchronous and metachronous metastases was divided by 2.5 for patients with synchronous status and 3.7 for patients with metachronous status.
In this study, the incidence of colorectal cancer with synchronous liver metastases changed little over time, whereas there was a 2-fold decrease in the probability of developing metachronous liver metastases. Survival improved substantially for patients with metachronous liver metastases, whereas improvement was more modest for those with synchronous metastases. The differences observed in the epidemiological features of synchronous and metachronous liver metastases from colorectal cancer may be useful for the design of future clinical trials.
尽管结直肠癌肝转移的治疗和预后已经比较明确，但对于同步和异时性肝转移的发生率、流行病学特征和结局仍缺乏比较性描述。同步和异时性肝转移患者的预后差异存在争议。
研究结直肠癌同步和异时性肝转移的发生率和结局的时间模式。
设计、设置和参与者：本基于人群的队列研究使用了法国一个地区性消化癌症登记处的信息，该登记处覆盖了 1082000 名居民。共纳入了 26813 例于 1976 年 1 月 1 日至 2018 年 12 月 31 日期间确诊为结直肠腺癌的患者。数据于 2022 年 2 月 7 日至 5 月 20 日进行分析。
计算了年龄标准化发病率。进行了单变量和多变量净生存分析。
在 26813 例结直肠癌患者（15032 例男性[56.1%]；中位[IQR]年龄为 73[64-81]岁）中，有 4546 例（17.0%）患者同时存在肝转移。男性的同步肝转移发生率为每 100000 人 6.9 例，女性为每 100000 人 3.4 例，自 2000 年以来并无显著变化。异时性肝转移的 5 年累积发生率从 1976 年至 1980 年期间的 18.6%（95%CI，14.9%-22.2%）降至 2006 年至 2011 年期间的 10.0%（95%CI，8.8%-11.2%）。诊断时的癌症分期是肝转移的最强风险因素；与诊断为 II 期癌症的患者相比，III 期癌症患者在 5 年内肝转移的风险增加了 2 倍（亚分布危险比，2.42；95%CI，2.08-2.82）。同步肝转移患者的 1 年净生存率为 41.8%，异时性肝转移患者的净生存率为 49.9%；5 年净生存率分别为 6.2%和 13.2%。在第一个（1976-1980）和最后一个（2011-2016）时期之间，同步和异时性肝转移患者死亡的调整比值分别下降了 2.5 倍和 3.7 倍。
在这项研究中，结直肠癌合并同步肝转移的发生率随时间变化不大，而发生异时性肝转移的可能性则降低了 2 倍。异时性肝转移患者的生存状况显著改善，而同步性肝转移患者的改善则较为温和。结直肠癌同步和异时性肝转移的流行病学特征差异可能有助于未来临床试验的设计。
