Comparison of complication rates of concurrent or sequential breast, plastic and gynecologic surgery using the PearlDiver-Mariner database

Introduction

Breast cancer is the most common malignancy affecting women, other than skin cancer, and 5–10% of new cases are attributed to hereditary mutations (1). While not all women with breast cancer will benefit from a risk-reducing salpingo-oophorectomy (RRSO), the National Comprehensive Cancer Network (NCCN) recommends women with a high-risk genetic mutation, such as BRCA, consider risk-reduction mastectomy (RRM) and RRSO to decrease the risk of development of breast or ovarian cancer (2). Ovarian suppression or RRSO may also be recommended to reduce recurrence in premenopausal women with a history of estrogen receptor (ER) positive breast cancer (3-5). After RRM or therapeutic mastectomy, patients may also be offered breast reconstruction.

In a short time span patients may be subjected to multiple procedures: mastectomy, breast reconstruction (possibly multistage), and RRSO. As these prophylactic procedures become more common, a better understanding of logistics, such as optimal timing, should be investigated. Concurrent surgeries may decrease patient burden with fewer trips to the operating room and may impact timing of adjuvant chemotherapy or radiotherapy, if required (6,7). Previous work has shown shortened time to adjuvant radiotherapy with concurrent surgery (7). Patients report high levels of satisfaction following concurrent surgery, and often report they would prefer concurrent surgery again (8,9). Finally, concurrent surgery may be more cost effective.

However, conflicting data exists on the safety and feasibility of mastectomy with or without reconstruction in combination with RRSO. While some studies report similar complication rates, others have shown higher complication rates for patients after concurrent breast, plastic and gynecologic surgery (7,10-13). Several retrospective, single institution studies have found that concurrent surgeries are a safe and feasible option for appropriate patients (6,8-10,12-18). However, these studies are small, ranging from 6–73 patients undergoing concurrent surgery. Two studies looking specifically at free flap and autologous breast reconstruction found no significant difference in wound complication rates when compared to patients who did not have a gynecologic surgery (6,14). Although longer operating times have been shown with concurrent surgery, the combined operating time of each sequential surgery is typically longer (10). An American College of Surgeon’s National Surgical Quality Improvement Program (NSQIP) analysis compared patients undergoing RRM with concurrent or sequential RRSO and found no significant difference in morbidity or postoperative complications (19). This study included 149 patients who underwent concurrent surgery, however, included patients without reconstruction and noted that RRSO patients were less likely to have reconstruction (19). In contrast, a single institution study with 58 patients who underwent concurrent surgery with reconstruction found significantly higher risk of complications, including infection and delayed wound healing, for concurrent surgery (7). A separate analysis of NSQIP identified 74 patient who underwent concurrent surgery with reconstruction found a significantly higher rate of postoperative complications for this group (11). However, this study used breast surgery alone, without plastic or gynecologic surgery, as the control group and did not provide details on included complications (11).

These studies are often limited secondary to a small sample size or include relatively few concurrent surgeries within their cohorts (6,12). There is inconsistency between studies on if procedures included were RRMs or therapeutic for breast malignancy, if there was reconstruction, and which procedural complications were included. Additionally, some studies were lacking a gynecologic surgery control group (6). There is concern that a gynecologic surgery concurrent with reconstruction options may increase the risk of patient complications, specifically infection or impaired wound healing, as it involves entering the abdomen (7,11).

Our objective in this study was to compare postoperative wound complication rates and cost effectiveness following reconstructive surgery for patients who underwent concurrent and sequential mastectomy, reconstruction, and RRSO using a large, national database. We aim to specifically compare patients who had all three surgery types and include both high-risk patients and those with a primary breast malignancy. While an individual’s risk assessment is dependent on multiple factors and decision to undergo prophylactic surgery should be a nuanced discussion between patient and provider on a case-by-case basis, our goal was to analyze postoperative wound complication rates for those who choose to undergo RRSO. Analysis using large, national database can provide overall trends, but may not be applicable to all patients on an individual level. We present this article in accordance with the STROBE reporting checklist (available at https://abs.amegroups.com/article/view/10.21037/abs-23-57/rc).

Methods

Data source

We utilized the PearlDiver-Mariner Database (PearlDiver) (PearlDiver Technologies, Colorado Springs, CO, USA) to conduct a retrospective cohort study. PearlDiver contains over 151 million patients from 2010 through mid-2020 and is a commercially available, deidentified, Health Insurance Portability and Accountability Act (HIPAA)-compliant database of insurance billing records nationally. This database includes commercial insurance, Medicare, Medicaid, other government insurance, and self-pay patients (20). Users can query the database for inpatient, outpatient, and prescription claims adjudicated by all insurance payers. The appropriate Institutional Review Board approved this study with an exemption as all data was deidentified prior to analysis.

Study population

Adult patients who underwent mastectomy, breast reconstruction, and salpingo-oophorectomy were identified using the appropriate 9^th and 10^th editions of the International Classification of Disease (ICD) procedure and the current procedural terminology (CPT) codes. Only patients with breast reconstruction and salpingectomy or salpingo-oophorectomy within 2 years of the date of mastectomy were included. Both implant and autologous breast reconstruction procedures were included; patients may have had multiple reconstruction procedures, including both implant and autologous reconstruction procedures. Patients with a history of endometrial, ovarian, or cervical cancer by ICD diagnosis code were excluded to ensure only prophylactic salpingectomy or salpingo-oophorectomy were captured. Patients who underwent prophylactic gynecologic surgery and any stage breast reconstruction within one operation as identified by ICD procedure or CPT codes were considered concurrent surgery. Patients with operations for prophylactic gynecologic surgery and breast reconstruction on different days were considered sequential surgery. Patients who underwent axillary lymph node dissection (ALND) or sentinel lymph node biopsy (SLNB) were identified by appropriate ICD or CPT codes. Mariner does not reliably separate by molecular subtype, therefore ER, progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) data were not included. Patient characteristics, including age, sex, Charlson Comorbidity Index (CCI), insurance type, and region, were obtained via PearlDiver and included in multivariable analysis. CCI is a standardized measure for patient disease burden. Race and ethnicity data is not collected by PearlDiver and therefore is not available for analysis. Socioeconomic status measures including mean family income, unemployment rate, high school graduation rate and Bachelor’s degree of the patient’s home location was collected. These data points are not patient level, but are based on the patient’s area of residence.

For both the concurrent surgery and sequential surgery groups, wound complications were identified by associated ICD diagnosis codes within 30 days of any stage breast reconstruction surgery to align with National Surgical Quality Improvement Program (NSQIP) standards. Wound complications included bleeding, hematoma, fat necrosis, seroma, implant infection, surgical site infection, and impaired wound healing or dehiscence. If present, each complication was counted once per patient, even if ICD codes were included on multiple encounters. In the PearlDiver data set, postoperative complications are not associated with a specific site (e.g., an ICD code for hematoma cannot be attributed to breast versus gynecologic surgical site). ICD diagnosis and CPT codes are listed in Table S1.

Cost analysis

We analyzed the total cost of care within 2 years from the date of mastectomy, which would encompass reconstruction and prophylactic gynecologic surgery according to our inclusion criteria. Reported costs are the actual reimbursement paid out by the insurance provider or by the patient, if uninsured. Analysis includes all diagnostic tests, hospitalizations, emergency department (ED) visits, outpatient clinic visits, medications, and procedures.

Costs were separated as inpatient, outpatient, and prescription costs. Inpatient costs included all costs incurred for services during a hospital admission. Outpatient costs include any costs while a patient was not admitted, including clinic visits, ambulatory surgeries, or ED visits if the patient was discharged from the ED. Prescription costs include all costs associated with a prescription filled at an outpatient pharmacy (including hospital outpatient pharmacies).

Statistical analysis

Statistical analysis was conducted using R built into the Bellweather software within PearlDiver. Categorical variables were summarized using frequencies and percentages, and continuous variables were summarized with median and standard deviation (SD). Wilcoxon rank-sum compared socioeconomic status measures. Multivariable logistic regression models analyzed factors associated with complications, including age, insurance plan, year of surgery, region, and comorbidity index. For each concurrent and sequential surgery, multivariable linear regression models analyzed differences in cost while controlling for age, insurance plan, year of surgery, region, and comorbidity index. There was no missing data in this insurance database, and we were unable to determine follow up status. All tests were two-sided, with P values of 0.05 or less considered to be statistically significant.

Ethical considerations

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by institutional ethics board of Rush University Medical Center and individual consent for this retrospective analysis was waived.

Results

Overall, 11,093 patients met inclusion criteria. Of these patients, 2,307 (21%) underwent concurrent reconstruction and prophylactic gynecologic surgery, while 8,786 (79%) patients underwent sequential surgery. All patients were female. Women were most commonly in their 40s and covered by private insurance. While the median CCI for both groups was 2, there was a higher portion of patients in the concurrent surgery group with a CCI of 0 (16% vs. 12%) and a higher portion of patients in the sequential group with a CCI ≥3 (42% vs. 48%) (P<0.001) (Table 1). Of these patients, 98% in the concurrent surgery group and 96% in the sequential surgery group had at least one tissue expander or implant-based breast reconstruction procedure (P<0.001); 20% of patients in both the concurrent surgery and sequential surgery group had an autologous tissue transfer as part of their reconstruction (P=0.84). Most patients had surgery due to cancer rather than prophylaxis (91% vs. 97%) (P<0.001) (Table 1). Patients who underwent concurrent surgery lived in areas with a generally higher mean family income ($75,611 vs. $72,320) (P<0.001), lower unemployment rate (7.04% vs. 7.23%) (P<0.001), higher rate of high school graduation (88.57% vs. 85.23%) (P=0.02), and higher rate of Bachelor’s degree (30.49% vs. 28.90%) (P<0.001) (Table 2).

Complication rates were higher for patients in the sequential surgery group for all complications (Table 3). The most common complication in both groups was impaired wound healing, but was significantly higher in the sequential surgery group (3.1% vs. 8.1%, P<0.001). Patients who underwent sequential surgery had significantly higher rates of hematoma (P<0.001), fat necrosis (P<0.001), seroma (P<0.001), implant infection (P<0.001), and surgical site infection (P<0.001).

After adjusting for age, CCI, insurance, and region, this trend remained significant (Table 4). Patients who underwent concurrent surgery had significantly lower odds of developing hematoma [adjusted odds ratio (aOR) 0.45, 95% CI: 0.30–0.65], fat necrosis (aOR 0.37, 95% CI: 0.27–0.51), seroma (aOR 0.38, 95% CI: 0.26–0.54), implant infection (aOR 0.33, 95% CI: 0.24–0.44), surgical site infection (aOR 0.42, 95% CI: 0.31–0.55), and impaired wound healing (aOR 0.37, 95% CI: 0.29–0.47).

Patients who underwent concurrent surgery cost $50,998 on average in the two years after mastectomy, while patients who underwent sequential surgery cost an average of $56,149. Inpatient and prescription costs were similar, and the largest difference was in the outpatient setting ($37,805 vs. $42,797) (Table 5). Multivariable cost analysis controlling for age, CCI, insurance and region is shown in Table 6. There was a significantly lower total cost and outpatient cost for patients who underwent concurrent surgery (P=0.04). A higher CCI was associated with higher cost for total, inpatient, outpatient, and prescription (P<0.0001). Increasing age was associated with a higher prescription cost (P<0.0001), but lower overall cost (P<0.0001) and outpatient cost (P<0.0001). Patients with private insurance paid more than those with Medicare for overall (P=0.005) and outpatient costs (P<0.0001).

Discussion

As genetic testing increases and more women elect to pursue risk-reduction surgery for breast and ovarian cancer, surgeons must evaluate the optimal sequence of these surgeries. While risk-reduction surgery is not necessary for all patients with breast cancer or the general population, for patients who may benefit from and desire RRSO, concurrent surgery may be advantageous as it can streamline the time and cost of multiple procedures and ultimately shorten time to adjuvant chemotherapy or radiotherapy, if needed. Through review of a large national patient database, we have shown that concurrent risk-reducing gynecologic surgery during any stage of breast reconstruction may be safe, cost-effective, and equivalent to sequential surgery with respect to surgical site complications.

To our knowledge, this study includes the largest group of patients who underwent concurrent surgery by a wide margin. Expansion of our patient population to include RRSO patients during any stage of reconstruction and including patients who underwent therapeutic mastectomy we can better evaluate the complication rates. Our conclusions are strengthened by a well-defined control cohort of similar patients who underwent the same set of surgeries: mastectomy, breast reconstruction and prophylactic gynecologic surgery. We show that concurrent surgery is not associated with an increased risk of wound healing complications. In fact, our data suggests there are more complications for patients who undergo sequential surgery. This difference may be secondary to concurrent surgeries being performed at large, high-volume academic centers, however this cannot be confirmed in the current study as PearlDiver does not provide hospital level data. The difference also may be influenced by having fewer comorbidities and higher socioeconomic status of the concurrent surgery group. More patients in the sequential surgery group had a diagnosis of breast cancer which may impact complication rates, however cannot be confirmed in this study as we cannot associate a complication with a specific surgery. A similar portion of patients in each group underwent ALND, but a higher percentage of patients underwent SLNB in the sequential surgery group. This difference in axillary surgery may influence complication rates, but the PearlDiver database does not associate complications with a specific surgery therefore cannot be assessed in this study. Patients in the concurrent surgery group were significantly more likely to undergo an implant-based breast reconstruction procedure (98% vs. 96%, P<0.001). However, individual patients may undergo a variety of combinations of implant-based and autologous reconstructive procedures, either simultaneously or in a staged fashion. Therefore, it is difficult to determine the influence of implant-based procedures on the difference of complication rates between the concurrent and sequential groups.

Concurrent surgery is also cost-effective over time. One study found the cost of concurrent reconstruction and RRSO to be more expensive than reconstruction without RRSO (6). However, this study did not include the cost of the RRSO as a second surgery. Our cost analysis covers two years following mastectomy in order to include all surgeries and effects of complications. We find that overall concurrent surgery saves over $5,000 compared to sequential surgery. Most of this cost savings comes in the outpatient setting, indicating decreased cost for office visits, ED visits, or ambulatory surgeries. Even when controlling for age, CCI, insurance and region, concurrent surgery is significantly less expensive than sequential surgery in total cost and outpatient cost. The PearlDiver database does not differentiate between surgery-related or primary care-related appointments, therefore this data represents the aggregate appointments and cost. Each patient will have different health needs, therefore individual cost may differ from the average of the group.

Although PearlDiver is a large, national database including patients in all 50 states, it is not inclusive of all patients across the United States. This is a cross-sectional study that may not be applicable to all patients, and is unable to analyze the specifics of any one individuals treatment plan and treatment outcomes (21). Additionally, as it standard for all insurance claims database studies, our data may be biased from coding variations for various complications and surgeries. We are unable to determine the molecular subtype of each patient’s cancer, which is an important aspect of their treatment plan. This data also suggests that younger, healthier, wealthier, and more educated women underwent concurrent surgery. These trends may indicate a selection bias for concurrent surgery by individual providers that impacts their recovery rates and confound our results. Additionally, a slightly higher percentage of women undergoing concurrent surgery had private insurance. Different insurance companies may have different regulations regarding coverage of prophylactic surgery, which may influence an individuals’ treatment choice.

The PearlDiver data set does not allow us to determine which surgery is associated with each complication. We are also unable to determine how many reconstructive surgeries each individual patient completed, but did show more patients in the concurrent surgery group had at least one implant-based reconstruction procedure and a similar number of patients underwent an autologous tissue transfer in each group. Additionally, there are complications following breast reconstruction that develop longer than 30 days postoperatively, which are not captured in this study. We evaluated 30 days postoperatively to align with a NSQIP level analysis. However, PearlDiver is advantageous over NSQIP as we have access to directly compare concurrent and sequential surgeries, which is not possible in the NSQIP database as we cannot identify patients who underwent sequential surgery. Finally, PearlDiver does not provide granular hospital or provider level details, which limits our ability to assess where concurrent surgeries are happening more often. Despite these limitations, this data represents the largest assessment of the safety and cost-effectiveness of concurrent surgery in the United States to date.

Conclusions

This large, national database study indicates mastectomy, breast reconstruction, and RRSO can be safely performed without an increased risk of wound healing complications. Integrating multidisciplinary surgical planning into practice is an important step in increasing access to concurrent surgery. Further research can help specify which patients may benefit most from concurrent surgery, including impacts from neoadjuvant chemotherapy and molecular subtype. The decision to undergo RRSO should be based on an individual’s risk factors and a risk-benefits discussion with their provider on a case-by-case basis, which concurrent surgery may be one aspect of this discussion.

Acknowledgments

The abstract of this study was accepted for publication at the Society of Surgical Oncology SSO 2023 - International Conference on Surgical Cancer Care, March 22–25, 2023, Boston, Massachusetts.

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://abs.amegroups.com/article/view/10.21037/abs-23-57/rc

Data Sharing Statement: Available at https://abs.amegroups.com/article/view/10.21037/abs-23-57/dss

Peer Review File: Available at https://abs.amegroups.com/article/view/10.21037/abs-23-57/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://abs.amegroups.com/article/view/10.21037/abs-23-57/coif). A.M. is a consultant for Merit Oncology and Kubtec. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by institutional ethics board of Rush University Medical Center and individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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