Are Gene-Specific Strategies Cost-Effective for Reducing Gynecologic Cancer Risk in Women With Lynch Syndrome?

Findings from a cost-effectiveness analysis support gene-specific surveillance and preventative strategies for reducing gynecologic cancer risk in women with Lynch syndrome (JAMA Netw Open. 2021;4[9]:e2123616. doi:10.1001/jamanetworkopen.2021.23616).

“With the expansion of multigene testing for cancer susceptibility, Lynch syndrome has become more readily identified among women,” explained Jason Wright, MD, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, New York, and colleagues.

“The condition is caused by germline pathogenic variants in DNA mismatch repair genes (ie, MLH1, MSH2, MSH6, and PMS2) and is associated with high but variable risks of endometrial and ovarian cancers based on genotype,” they continued.

This study aimed to assess the cost-effectiveness of genotype-specific surveillance and preventative strategies for gynecologic cancers associated with Lynch syndrome.

A cohort-level Markov simulation model was developed for Lynch syndrome-associated gynecologic cancers for each gene.

The study interventions were hysterectomy and bilateral salpingo-oophorectomy (hyst-BSO) at ages 35, 40, or 50 years with or without annual surveillance initiated at ages 30 or 35 years or hysterectomy and salpingectomy at age 40 years and delayed oophorectomy until age 50 years (two-stage approach).

The primary study end point was the incremental cost-effectiveness ratio (ICER) between the two strategies.

For patients with MLH1 and MSH6 variants, the optimal strategy was the two-stage approach, with ICERs of $33,269 and $20,008, respectively, compared to hyst-BSO at age 40 years. Although cost-effective, the two-stage approach was associated with increased cancer incidence and mortality than hyst-BSO for patients with MLH1 variants (incidence: 7.76% vs 3.84%; mortality: 5.74% vs 2.55%) and MSH6 variants (incidence: 7.24% vs 4.52%; mortality: 5.22% vs 2.97%).

For patients with MSH2 variants, the optimal strategy was hyst-BSO at age 40 years, with an ICER of $5180 compared with hyst-BSO at age 35 years. In additiona, hyst-BSO at 40 years was associated with an estimated cancer incidence of 4.42% and cancer mortality of 2.97%.

For patients with PMS2 variants, hyst-BSO at age 50 years was optimal and all other strategies were dominated. Hyst-BSO at age 50 years was associated with an estimated cancer incidence of .68% and cancer mortality of .29%.

“These findings suggest that gene-specific preventive strategies for gynecologic cancers in LS [Lynch syndrome] may be warranted and support hyst-BSO at age 40 years for individuals with MSH2 variants,” concluded Dr Wright and colleagues.

“For individuals with MLH1 and MSH6 variants, these findings suggest that a novel 2-stage surgical approach with delayed oophorectomy may be an alternative to hyst-BSO at age 40 years to avoid early menopause, and for individuals with PMS2 variants, the findings suggest that hyst-BSO may be delayed until age 50 years,” they continued.—Janelle Bradley