Ovarian cancer prevention through opportunistic salpingectomy during abdominal surgeries: A cost-effectiveness modeling study

Abstract

Background: There is indication that the fallopian tubes might be involved in ovarian cancer pathogenesis and their removal reduces cancer risk. Hence, bilateral salpingectomy during hysterectomy or sterilization, so called opportunistic salpingectomy (OS), is gaining wide acceptance as a preventive strategy. Recently, it was discussed whether implementation of OS at other gynecologic surgery, e.g., cesarean section, endometriosis excision or myomectomy and even at non-gynecologic abdominal surgery such as cholecystectomy or appendectomy for women with completed family could be feasible. This modeling analysis evaluated the clinical and economic potential of OS at gynecologic and abdominal surgeries.

Methods and findings: A state transition model representing all relevant health states (healthy, healthy with hysterectomy or tubal ligation, healthy with other gynecologic or non-gynecologic abdominal surgery, healthy with hysterectomy and salpingectomy, healthy with salpingectomy, healthy with hysterectomy and salpingo-oophorectomy, ovarian cancer and death) was developed and informed with transition probabilities based on inpatient case numbers in Germany (2019). Outcomes for women aged 20-85 years were simulated over annual cycles with 1,200,000 million individuals. We compared four strategies: (I) OS at any suitable abdominal surgery, (II) OS only at any suitable gynecologic surgery, (III) OS only at hysterectomy or sterilization, and (IV) no implementation of OS. Primary outcome measures were prevented ovarian cancer cases and deaths as well as the incremental cost-effectiveness ratio (ICER). Volume of eligible interventions in strategy I was 3.5 times greater than in strategy III (286,736 versus 82,319). With strategy IV as reference, ovarian cancer cases were reduced by 15.34% in strategy I, 9.78% in II, and 5.48% in III. Setting costs for OS to €216.19 (calculated from average OS duration and operating room minute costs), implementation of OS would lead to healthcare cost savings as indicated by an ICER of €-8,685.50 per quality-adjusted life year (QALY) gained for strategy I, €-8,270.55/QALY for II, and €-4,511.86/QALY for III. Sensitivity analyses demonstrated stable results over a wide range of input parameters with strategy I being the superior approach in the majority of simulations. However, the extent of cancer risk reduction after OS appeared as the critical factor for effectiveness. Preventable ovarian cancer cases dropped to 4.07% (I versus IV), 1.90% (II versus IV), and 0.37% (III versus IV) if risk reduction would be <27% (hazard ratio [HR] > 0.73). ICER of strategies I and II was lower than the 2× gross domestic product per capita (GDP/C) (€94,366/QALY, Germany 2022) within the range of all tested parameters, but strategy III exceeded this threshold in case-risk reduction was <35% (HR > 0.65). The study is limited to data from the inpatient sector and direct medical costs.

Conclusions: Based on our model, interdisciplinary implementation of OS in any suitable abdominal surgeries could contribute to prevention of ovarian cancer and reduction of healthcare costs. The broader implementation approach demonstrated substantially better clinical and economic effectiveness and higher robustness with parameter variation. Based on a lifetime cost saving of €20.89 per capita if OS was performed at any suitable abdominal surgery, the estimated total healthcare cost savings in Germany could be more than €10 million annually.

Fig 1. The state-transition diagram of the opportunistic salpingectomy (OS) decision-analytic model, presented here in simplified form, represents the possible health states associated with surgery or the absence of it.

OS is thought to be performed exclusively on occasion of a gynecologic or non-gynecologic abdominal intervention that is medically necessary, or if a women decides to have permanent contraception. Women stay in each state until a relevant event occurs. Transition is only allowed if it leads to increased ovarian cancer risk reduction. Four strategies are compared: (I) OS performed at any suitable abdominal surgical intervention (Gyn. + Non-Gyn.), (II) OS performed only at any suitable gynecologic surgery (Gyn.), (III) OS performed only at hysterectomy or as an alternative to tubal ligation for sterilization (current practice in some countries) and (IV) no implementation of OS (reference strategy). Women can finally end up in the states “death of other causes” or “death of ovarian cancer” as absorbing states. Hazard ratios (HRs) for ovarian cancer risk after the respective interventions according to Falconer and colleagues [11]. Gyn., gynecologic; Non-Gyn., non-gynecologic.

Fig 2. Age-dependent yearly probabilities (risk) for surgery with occasion for opportunistic salpingectomy and risk of ovarian cancer.

Calculated from pre-pandemic case numbers (year 2019) obtained from the Federal Statistical Office of Germany and the German Center for Cancer Registry Data. Non-gynecologic (non-gyn) abdominal surgery included cholecystectomy, hernia closure, bariatric surgery and scheduled uncomplicated appendectomy starting from 40 years of age. Other gynecologic (other gyn) surgery includes cesarean section, ovarian cyst removal, inpatient endometriosis surgery, open abdominal or laparoscopic myomectomy and uterus fixation starting from age 40 years. HE+BSO, hysterectomy with bilateral salpingo-oophorectomy.

Fig 3. Results of one-way deterministic sensitivity analyses of the decision-analytic model for opportunistic salpingectomy (OS).

The incremental cost-effectiveness ratio (ICER) was calculated for strategy I (OS at any suitable gynecologic and non-gynecologic abdominal surgery), strategy II (OS at any suitable gynecologic surgery) and strategy III (OS only at hysterectomy and in lieu of tubal ligation for sterilization) compared to strategy IV (no OS) as reference. “Base case” refers to a simulation with base case values for all parameters. Parameters were varied within the range of measures of precision found in the literature. (A) Variation of ovarian cancer risk after salpingectomy [11]. (B) Variation of time from surgery to effect of OS (latency period) [13]. (C) Variation of OS costs [27,49]. (D) Variation of ovarian cancer follow-up costs ([50] and own calculations). QALY, quality-adjusted life year. Gross domestic product per capita in Germany was €47,183 in the year 2022 [51].