Costs of Cancer Prevention: Physical and Psychosocial Sequelae of Risk-Reducing Total Gastrectomy

Abstract

Purpose: Risk-reducing surgery for cancer prevention in solid tumors is a pressing clinical topic because of the increasing availability of germline genetic testing. We examined the short- and long-term outcomes of risk-reducing total gastrectomy (RRTG) and its lesser-known impacts on health-related quality of life (QOL) in individuals with hereditary diffuse gastric cancer syndrome.

Methods: Individuals who underwent RRTG as part of a single-institution natural history study of hereditary gastric cancers were examined. Clinicopathologic details, acute and chronic operative morbidity, and health-related QOL were assessed. Validated questionnaires were used to determine QOL scores and psycho-social-spiritual measures of healing.

Results: One hundred twenty-six individuals underwent RRTG because of a pathogenic or likely pathogenic germline CDH1 variant between October 2017 and December 2021. Most patients (87.3%; 110/126) had pT1aN0 gastric carcinoma with signet ring cell features on final pathology. Acute (<30 days) postoperative major morbidity was low (5.6%; 7/126) and nearly all patients (98.4%) lost weight after total gastrectomy. At 2 years after gastrectomy, 94% (64/68) of patients exhibited at least one chronic complication (ie, bile reflux, dysphagia, and micronutrient deficiency). Occupation change (23.5%), divorce (3%), and alcohol dependence (1.5%) were life-altering consequences attributed to total gastrectomy by some patients. In patients with a median follow-up of 24 months, QOL scores decreased at 1 month after gastrectomy and returned to baseline by 6-12 months.

Conclusion: RRTG is associated with life-changing adverse events that should be discussed when counseling patients with CDH1 variants about gastric cancer prevention. The risks of cancer-prevention surgery should not only be judged in the context of likelihood of death due to disease if left untreated, but also based on the real consequences of organ removal.

Trial registration: ClinicalTrials.gov NCT03030404.

FIG 1.

Change in BMI from baseline to 12 months after RRTG in 126 patients by sex (males = blue, females = red). Underweight BMI is defined as ≤18.4 kg/m², normal BMI is 18.5-24.9 kg/m², overweight BMI is 25-29.9 kg/m², and obese BMI is >30 kg/m². RRTG, risk-reducing total gastrectomy.

FIG 2.

Schematic demonstrating the chronic sequelae and impact on multiple organ systems after risk-reducing total gastrectomy.

FIG 3.

FACT-G and FACT-Ga questionnaires included 27 and 46 items, respectively, scored on a five-point Likert scale from not at all (0) to very much (4). The FACT-Ga TOI was calculated by adding physical and functional well-being scores. The FACT-G total score included physical, social, emotional, and functional well-being scores. The FACT-Ga total score combined the FACT-G score with a 19-item gastric cancer subscale. Examples of physical, social, emotional, and functional well-being items were “I have a lack of energy,” “I get emotional support from my family,” “I worry that my condition will get worse,” and “I am able to enjoy life,” respectively. The 19-item gastric cancer subscale score included disease-specific questions such as “I am bothered by reflux or heartburn” and “My digestive problems interfere with my usual activities.” (A) FACT-G, (B) FACT-Ga, and (C) TOI scores were calculated in 54 patients with germline CDH1 variants at baseline and 1, 3, 6, 12, and 24 months after risk-reducing total gastrectomy. NIH-HEALS questionnaire included 35 items scored on a five-point Likert scale from strongly disagree (1) to strongly agree (5) with four items reverse scored (6, 23, 28, and 34). (D) Total score and subscores (E) connection to a higher power, community, and family, (F) reflection and introspection or the ability to find meaning and purpose in activities that connect mind and body, and (G) trust and acceptance that caregivers, friends, and family will respond when needs arise were calculated. Examples of questionnaire items included “My situation strengthened my connection to a higher power” for the connection factor, “I gain awareness from self-reflection” for the reflection and introspection factor, and “I am content with my life” for the trust and acceptance factor. (D) Total score and (E-G) subscores were calculated in 54 patients with germline CDH1 variants at baseline and 1, 3, 6, 12, and 24 months after risk-reducing total gastrectomy. *P ≤ .05, **P ≤ .01, ***P ≤ .001. FACT-G, Functional Assessment of Cancer Therapy General; FACT-Ga, Functional Assessment of Cancer Therapy-Gastric; NIH-HEALS, National Institutes of Health Healing Experience of All Life Stressors; TOI, Trial Outcome Index.