Assessing Effectiveness of Colonic and Gynecological Risk Reducing Surgery in Lynch Syndrome Individuals

SIMPLE SUMMARY: Colorectal and endometrial cancers are the most important life-threating risk in Lynch syndrome subjects, with incidences at 75 years as high as 40–60%. However, surveillance has shown to be ineffective. Risk reducing surgeries are an option in Lynch Syndrome (LS) individuals to decrease incidence of this type of cancers. In this manuscript, we have analyzed the rates of colorectal and gynecological cancer in 976 LS individuals after a mean follow-up of 10.2 years (patients under regular surveillance or after a risk reducing surgery). We can confirm in the largest study published up to the present in a single-institution that risk reducing surgeries are effective in decreasing incidence of colorectal and gynecological cancer in all LS carriers. Moreover, is the first report showing a decrease in all-cause mortality cumulative incidence in females with Lynch syndrome that undergo gynecological risk reducing surgery. ABSTRACT: Background: Colorectal (CRC) and endometrial cancer (EC) are the most common types of cancer in Lynch syndrome (LS). Risk reducing surgeries (RRS) might impact cancer incidence and mortality. Our objectives were to evaluate cumulative incidences of CRC, gynecological cancer and all-cause mortality after RRS in LS individuals. Methods: Retrospective analysis of 976 LS carriers from a single-institution registry. Primary endpoints were cumulative incidence at 75 years of cancer (metachronous CRC in 425 individuals; EC and ovarian cancer (OC) in 531 individuals) and all-cause mortality cumulative incidence, comparing extended (ES) vs. segmental surgery (SS) in the CRC cohort and risk reducing gynecological surgery (RRGS) vs. surveillance in the gynecological cohort. Results: Cumulative incidence at 75 years of metachronous CRC was 12.5% vs. 44.7% (p = 0.04) and all-cause mortality cumulative incidence was 38.6% vs. 55.3% (p = 0.31), for ES and SS, respectively. Cumulative, incidence at 75 years was 11.2% vs. 46.3% for EC (p = 0.001) and 0% vs. 12.7% for OC (p N/A) and all-cause mortality cumulative incidence was 0% vs. 52.7% (p N/A), for RRGS vs. surveillance, respectively. Conclusions: RRS in LS reduces the incidence of metachronous CRC and gynecological neoplasms, also indicating a reduction in all-cause mortality cumulative incidence in females undergoing RRGS.