Outpatient opioid use after minimally invasive surgery for lung cancer: a Surveillance, Epidemiology, and End Results-Medicare cohort study

Introduction

Opioids remain a mainstay for managing postoperative pain following thoracic surgery. However, their use is associated with increased morbidity and mortality due to cognitive effects, tolerance, and addiction (1). Postoperative opioid prescribing practices vary widely, and although larger prescriptions are often given to ensure adequate pain control, they are associated with an increased risk of prolonged use and have inadvertently contributed to the ongoing opioid crisis (2-7). In response, evidence-based guidelines have been developed to standardize opioid prescribing practices and reduce the risks associated with overprescribing (8).

This effort is particularly important in thoracic surgery, where patients are less likely to use opioids preoperatively, yet experience higher rates of prolonged postoperative use compared to other surgical populations (9-11). Current guidelines for opioid prescriptions typically differentiate between open and minimally invasive approaches, without distinguishing between minimally invasive approaches (12). While prior studies found lower postoperative inpatient opioid use with robotic-assisted surgery (RAS) as compared to open and video-assisted thoracoscopic surgery (VATS), the impact of surgical approach on outpatient opioid prescriptions following discharge remains unknown (13). This distinction provides additional insight into patient risk, as outpatient prescriptions carry the potential for persistent opioid use, misuse, overdose, and unintended familial exposure in a setting with less monitoring than inpatient administration (2-7,14-16). In this study, we aimed to compare postoperative outpatient prescription opioid use following RAS and VATS lung resection for non-small cell lung cancer (NSCLC) once patients are discharged from hospital. We hypothesize that RAS is associated with fewer outpatient opioid prescription fill as compared to VATS. We present this article in accordance with the STROBE reporting checklist (17) (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1443/rc).

Methods

Data source

The study used the Surveillance, Epidemiology, and End Results (SEER) cancer registry, linked with Medicare claims databases. The SEER database supported by the National Cancer Institute’s Surveillance Research Program is an epidemiologic surveillance system consisting of population-based cancer registries that cover approximately 48% of the United States (U.S.) population (18). The SEER-Medicare linked database contains clinical, demographic, and cause of death information for persons with cancer, and the Medicare claims for covered health care services from Medicare eligibility date until death (19). This study was a retrospective, population-based cohort study. In accordance with 45 Code of Federal Regulations (CFR) §46, it was exempted from review by an institutional review board (20). The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Patient selection

The study population for this study was elderly Medicare beneficiaries (≥66 years old) with histologically confirmed stage 0–III NSCLC who underwent minimally invasive (RAS or VATS) lobectomy or sub-lobar resection between January 2016 and July 2020. The admission date for lobectomy or sub-lobar resection was considered the index date for the study. As shown in the study design (Figure 1), patients were retrospectively assessed for 12 months before admission for determination of eligibility criteria and baseline characteristics, and then assessed for 180 days after discharge for determination of study outcomes. Continuous insurance enrollment in Medicare Part A/B (medical coverage) and Medicare Part D (prescription coverage), and absence of health maintenance organization (HMO) enrollment were required to ensure complete data was captured. Exclusion criteria included a metastatic lung cancer diagnosis, neoadjuvant therapy, a diagnosis of prior chronic pain diagnosis, or opioid abuse history, or a chronic opioid prescription fill behavior defined as ≥120 cumulative days of opioid supply before the perioperative period (21). These exclusions allow for a clearer assessment of the impact of surgical approach on post-surgical opioid prescription fill among patients who would not need opioids otherwise. All patients who fulfilled the eligibility criteria were included in the study. Patients were assigned to either the RAS or VATS group based on their surgical approach. This was an intention-to-treat analysis and cases that resulted in conversion were included in the original cohort. All codes used for cohort identification and surgical approach definition are shown in Table S1.

Figure 1 Study design. MME, morphine milligram equivalent; Rx., prescription.

Outcome variables

The study examined postoperative outpatient opioid prescription fill in the immediate (0 to 42 days postop), short-term (43 to 90 days postop), and long-term (91 to 180 days postop) periods. Three types of opioid prescription fill outcomes were assessed in similar manner for all patients: any opioid fill, abuse-potential opioid fill, and high-dose opioid fill. Abuse-potential opioid fill was defined as prescription fill for controlled substance schedule II or III opioids, per the Drug Enforcement Administration (DEA) classification, and high-dose opioid fill was defined as prescription fill with a calculated ≥50 morphine milligram equivalent (MME) dosing per day. These definitions were considered to represent high-risk opioid use because of the potential of abuse with schedule II/III opioids, and increased overdose risk with ≥50 MME per day intake with minimal additional benefit to the patient (22,23).

Study covariates

Patients’ demographic, clinical, and treatment characteristics were assessed as study covariates. Demographic characteristics included age (66–74, 75–84, or ≥85 years), sex, race/ethnicity (White, Black, Hispanic, or other), marital status (married/with partner, not-married, or never-married), residence census region, metropolitan residence, year of surgery, and census tract socioeconomic status (SES). SES variables included median household income, percentage of no high school education, and percentage below poverty level. Income was inflation-adjusted to 2020 U.S. dollars using Medical Consumer Price Index (24). All SES variables were categorized into terciles for the study population. Clinical characteristics included tumor characteristics from the SEER registry and other diagnoses based on the claims file (Table S2). These were tumor site (lower, middle, upper lobe, or others), nodule size (1 to 20, 21 to 30, 31 to 40, 41 to 50, ≥51 mm, or unknown), grade (well, moderately, or poorly/not-differentiated, or unknown), histology (adenocarcinoma, squamous, or others), cancer stage at diagnosis (stage 0/I, stage II, or stage III), Charlson’s comorbidity index (CCI), and diagnosis of tobacco abuse/history, alcohol abuse/dependence, mental disorder, and obesity/overweight status. Treatment characteristics included procedure type (lobectomy or sub-lobar resection), prior non-chronic opioid use, number of unique opioids prescribed, and days of supply of opioids at discharge as a proxy for prescriber behavior. In addition, hospital surgical volume was measured by the number of lobar or sub-lobar resections performed at the hospital in the 1-year before admission, categorized into terciles.

Statistical analysis

Descriptive analyses of demographic and clinical characteristics were conducted in the entire study population and by surgical approach (RAS vs. VATS). To adjust for differences in sample characteristics between groups and minimize potential sample selection bias, we used an inverse-probability of treatment weighting (IPTW) technique before examining the association between surgical approach and opioid uses. A total of 25 patients with missing income (n=15), education data (n=12), region (n=5), or surgical volume (n=3) were removed from analysis to improve model fit. A separate category for “unknown” was created for other variables with missing values. Logistic regression was used to estimate probability of treatment (RAS vs. VATS) with all baseline characteristics included as covariates, and inverse probabilities were assigned to patients. IPTW adjustment creates a synthetic sample which is independent of covariates allowing for unbiased estimate of average treatment effects (25). The weighted distribution of each sample characteristics by surgical approach was examined, and the balance between groups was assessed using standardized mean differences (SMDs) before and after IPTW, using SMD of <0.1 as an indicator of sufficient balance. Any characteristics left unbalanced after IPTW were added as additional covariate in the outcome analysis. For the outcome analysis, IPTW adjusted logistic regression was performed separately for each binary outcome (any opioid, abuse-potential opioid, and high-dose opioid use). Sub-group analyses were performed by procedure type (lobectomy and sub-lobar resection), adjuvant therapy (treated and not-treated), and cancer stage (stage 0/I and stage II/III), using the same statistical approach. For an ad-hoc analysis of cumulative quantity of opioids filled by month, a generalized linear model with gamma distribution and log-link was used to estimate marginal means MME at each month postop, and the mean adjusted cumulative quantity of opioids filled by surgical approach was plotted over time.

Results

There were 14,853 patients aged ≥66 years with histologically confirmed stage 0–III NSCLC who had minimally invasive (RAS or VATS) inpatient lobectomy or sub-lobar resection between January 2016 and July 2020 in the SEER-Medicare database. After applying exclusion criteria, 4,243 patients were included in the analysis, of whom 27.3% underwent RAS (n=1,157) and 72.7% underwent VATS (n=3,086) (Figure 2). As shown in Table 1, the majority of the cohort was female (58%), aged 66–74 years (57%), and had a history of tobacco abuse (68%). Nearly half of the patients (49%) had tumor ≤20 mm in size and 78% underwent lobectomy. Approximately 71% of the sample had opioid prescription fill in the immediate postop period (0 to 42 days), 12% in the short-term period (43–90 days), and 13% in the long-term period (91 to 180 days). As shown in Table S3, all baseline characteristics were balanced between RAS and VATS groups after IPTW adjustment (SMD <0.1), except for tumor grade (SMD =0.102). Tumor grade was therefore included as additional covariate in the outcome regression model (Figure 3).

Figure 2 Sample selection flowchart. dx., diagnosis; HMO, health maintenance organization; RAS, robotic-assisted surgery; SEER, Surveillance, Epidemiology, and End Results; VATS, video-assisted thoracoscopic surgery.

Figure 3 Standardized difference between RAS and VATS before and after IPTW. IPTW, inverse-probability of treatment weighting; RAS, robotic-assisted surgery; VATS, video-assisted thoracoscopic surgery.

IPTW adjusted results comparing opioid prescription fills between RAS and VATS are presented in Table 2. In the immediate postop period (0 to 42 days), RAS and VATS patients had comparable fill of any opioid prescription [70% vs. 71%; odds ratio (OR) =0.94; P=0.40]. However, RAS patients were less likely to fill abuse-potential opioids (59% vs. 63%, OR =0.85, P=0.02) and high-dose opioids (14% vs. 18%, OR =0.76, P=0.006) as compared to VATS. In the short-term postop period (43–90 days), RAS patients were approximately 25% less likely to fill any opioid prescription than VATS patients [9.8% vs. 13%; OR =0.76; 95% confidence interval (CI): 0.60–0.95; P=0.02]. Further, RAS was associated with less likelihood of abuse-potential opioid fill (6.8% vs. 10%; OR =0.65; 95% CI: 0.50–0.85; P=0.002) and high-dose opioid fill (<1.0% vs. 1.9%; OR =0.46; 95% CI: 0.22–0.88; P=0.03) as compared to VATS. There was no significant difference in long-term (91 to 180 days) opioid fill between RAS and VATS (P>0.05). An ad-hoc analysis of the cumulative quantity of opioid filled (in MME) by patients who were started on opioid treatment demonstrated that VATS patients filled a higher cumulative quantity of opioids than RAS patients over time (Figure 4). In a sensitivity analysis, excluding patients who were converted to open procedures resulted in no substantial change in the findings (Table S4).

Figure 4 Monthly cumulative quantity of opioids filled after IPTW adjustment. CI, confidence interval; IPTW, inverse-probability of treatment weighting; MME, morphine milligram equivalent; RAS, robotic-assisted surgery; VATS, video-assisted thoracoscopic surgery.

Sub-group analyses were performed based on procedure type (lobectomy and sub-lobar resection, Table S5), adjuvant therapy (treated, and not-treated, Table S6), and clinical cancer stage (stage 0/I and stage II/III, Table S7). In the lobectomy subgroup, RAS was associated with 33% lower odds of abuse-potential (P=0.005) and 61% lower odds of high-dose opioid use (P=0.02) in the short-term period as compared to VATS. In the no-adjuvant therapy sub-group, RAS was associated with 33% lower odds of any opioid (P=0.01), 30% lower odds of abuse-potential (P=0.006), and 74% lower odds of high-dose (P=0.02) opioid uses in the short-term period as compared to VATS. In the stage-0/I cancer cohort, RAS was associated with 35% lower odds of any opioid (P=0.004), 40% lower odds of abuse-potential (P=0.003), and 75% lower odds of high-dose (P=0.02) opioid uses in the short-term period than VATS. There were no significant differences in the short-term opioid uses between RAS and VATS among the sub-lobar resection, adjuvant therapy, and stage-II/III cancer cohort sub-groups (P>0.05).

When examining long-term opioid use (91–180 days postop) in our subgroup analysis, we found that opiate use was significantly lower for RAS compared to VATS within the adjuvant therapy sub-group. Specifically, RAS was associated with up to 30% lower odds of any opioid use (OR =0.70; 95% CI: 0.49–0.99; P=0.047) and 42% lower odds for abuse potential opioid use (OR =0.58; 95% CI: 0.38–0.85; P=0.007) compared to VATS.

Discussion

In this large, population-based cohort study of elderly lung cancer patients undergoing minimally invasive thoracic surgery in the U.S., RAS was associated with less opioid exposure compared to VATS. Notably, while overall opioid use during the immediate postoperative period (up to 42 days) was similar between groups, RAS patients received fewer high-dose and abuse-potential opioids. Differences became more pronounced in the 43–90 days postop window, where RAS was associated with significantly lower rates of overall opioid use, as well as high-dose and abuse-potential prescriptions. Similar patterns were identified across multiple subgroups, including patients undergoing lobectomy, those not receiving adjuvant therapy, and patients with early-stage lung cancer. We found no significant differences in the other subgroup analyses which could be due to sample size. We suggest further research among these subgroups with larger sample sizes. No significant difference in long-term opioid use was observed in the overall cohort, but RAS was associated with significantly lower long-term use of any opioid, and abuse-potential opioids in patients receiving adjuvant therapy.

While the benefits of minimally invasive techniques over open surgery for postoperative pain are well-established, there is limited research on the differences between minimally invasive approaches. As a result, current prescribing guidelines differentiate between open and minimally invasive approaches, but not between VATS and RAS (12). Our results suggest that such differentiation may be warranted, as RAS may confer additional opioid-sparing benefits beyond those of VATS. While the need for any opioid therapy during immediate recovery is similar following both minimally invasive resections, VATS requires a longer duration and higher dosage of opioids, including those with greater abuse potential, compared to RAS. A potential explanation for the observed differences is that RAS is a completely port-based approach, which may reduce intraoperative trauma at the chest wall and, in turn, lead to less postoperative discomfort and faster recovery (26-30). Additionally, the robotic system’s fixed remote center of motion (remote centering of the trocar) may further minimize surrounding tissue damage during the operation and minimize the fulcrum effect of instruments passing through the intercostal space (31). Given the risks of opioid use, especially among older adults, incorporating the type of minimally invasive surgical modality into postoperative opioid prescribing protocols could enhance efforts to reduce opioid use (6,32,33). Specifically, patients undergoing RAS may be appropriate candidates for shorter-duration or lower-dosage opioid prescriptions, thereby limiting unnecessary exposure to high-risk medications. Furthermore, these results may inform shared decision-making discussions between patients and surgeons regarding the choice of surgical approach.

In comparing long-term opioid use, a significant difference between VATS and RAS was found only in patients who received adjuvant therapy. This aligns with existing literature indicating that adjuvant therapy increases the risk of chronic pain following VATS (34). The differences observed between VATS and RAS in this population may be attributed to the reduced operative trauma associated with RAS, as described above, which are magnified by the use of adjuvant therapy with its potential for neuralgia. While long-term opioid use is often a primary concern, it is equally important to recognize the potentially life-altering consequences of even short-term opioid exposure. Short term opioid use following major surgery has been linked to risks of overdose, readmission, and subsequent opioid dependence among family (14-16). Our findings highlight RAS’s potential to reduce opioid use compared to VATS, especially during the perioperative period and short-term recovery.

This study has limitations inherent to its retrospective design and dependence on a large database. To address potential bias associated with the retrospective design, we conducted an IPTW adjusted analysis to control for known confounders. However, despite this adjustment, there may still be residual or unidentified confounders. In addition, analyses of the Medicare claims relies on diagnostic and procedural coding, which can be prone to inaccuracies or inconsistencies. It is worth to note that Medicare claims data has low sensitivity in measuring behavioral factors such as tobacco abuse/history, alcohol abuse/dependence, mental disorder, and obese/overweight status, and that analysis of hospital volume was limited to facilities located in SEER areas. Further, opioid prescription fill is a proxy measure for opioid use and does not account for in-hospital opioid use. A prior study has reported higher in-hospital opioid use with VATS as compared to RAS using hospital discharge database (13). While we may assume opioid use in the presence of continued prescription fill in the 43 to 90 days period, this may not necessarily be true. Due to the limitation of databases used in the current study, we were unable to examine in-hospital opioid use. In addition, humanistic outcomes such as pain score, functional recovery and quality of life were not assessed in this study. Although a prior study has reported lower pain score and improved quality of life after RAS compared to VATS (35), further studies are recommended to add support to our findings. Finally, the study utilized a large, nationally representative dataset, which enhances the robustness and generalizability of the findings. However, it was limited to Medicare beneficiaries, which may limit generalizability to younger patients or those outside the U.S. healthcare system.

Conclusions

In conclusion, our study demonstrates that RAS is associated with lower opioid use compared to VATS, particularly with regard to high-dose and abuse-potential opioids. Our findings suggest that RAS may minimize opioid exposure and potentially help reduce opioid overutilization. Distinguishing between RAS and VATS minimally invasive surgical techniques in opioid prescribing guidelines may further optimize patient care and reduce opioid-related complications.

Acknowledgments

This study used the linked SEER-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. The authors acknowledge the efforts of the National Cancer Institute; Information Management Services (IMS), Inc.; and the Surveillance, Epidemiology, and End Results (SEER) Program tumor registries in the creation of the SEER-Medicare database. The collection of cancer incidence data used in this study was supported by the California Department of Public Health pursuant to California Health and Safety Code Section 103885; Centers for Disease Control and Prevention’s (CDC) National Program of Cancer Registries, under cooperative agreement 1NU58DP007156; the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program under contract HHSN261201800032I awarded to the University of California, San Francisco, contract HHSN261201800015I awarded to the University of Southern California, and contract HHSN261201800009I awarded to the Public Health Institute. The ideas and opinions expressed herein are those of the author(s) and do not necessarily reflect the opinions of the State of California, Department of Public Health, the National Cancer Institute, and the Centers for Disease Control and Prevention or their Contractors and Subcontractors.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1443/rc

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1443/prf

Funding: Intuitive Surgical sponsored access to the SEER-Medicare database.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1443/coif). A.M. indirectly receives funding for research through the Intuitive Surgical-UCSF Simulation-Based Surgical Education Research Fellowship. G.M. reports that Intuitive Surgical sponsored access to the SEER-Medicare database, and article processing charges. G.M., T.R., I.F.S. are employed by Intuitive Surgical and report stock or stock options with Intuitive Surgical. D.S.O. has dual employment at Intuitive Surgical as a medical advisor and at City of Hope Cancer Center, California. D.S.O. reports stock or stock options with Intuitive Surgical. J.R.K. is a consultant for Intuitive Surgical and receives support from Intuitive Surgical Corp. for attending meetings and/or travel. J.R.K. is on the ION Medical Advisory Board. The authors have no other 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 and its subsequent amendments.

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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