Increases in the Association Between the Rates of Synchronous and Metachronous Metastases over Time

Background: This study investigates the association between synchronous and metachronous metastases across various cancer types, evaluating whether that relationship has evolved over time. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER)-8 dataset from 1975 to 2020 were retrospectively reviewed. For each of the 18 solid tumor types, the crude rates of synchronous and metachronous metastases were estimated from the SEER database. For each of the years assessed (from 1975 to 2015 at 10-year increments), linear regression analyses were conducted to quantify the relationship between the rates of metachronous metastasis and synchronous metastasis across all cancer sites. The degrees of association over time were compared using a Fisher's z-transformation. Results: At all time points considered, there was a significant association between the rates of metachronous and synchronous metastases (all p values < 0.05 for 5-year follow-up data). The degree of that association tended to increase over time (R = 0.59, 0.60, 0.66, 0.80, and 0.87 for 1975, 1985, 1995, 2005, and 2015, respectively), with the p value of the z-score comparing the many R values over time varying from 0.04 to 0.48. Conclusions: There appears to be an increasing association between the rates of synchronous and metachronous distant metastases over time. The exact cause of this increasing association is unknown. However, it appears to have occurred somewhat contemporaneous with the increasing use of more-accurate imaging studies (e.g., FDG-PET). Newer, targeted radiotracers for PET may provide the landscape for a prospective evaluation of the role of imaging.