Minimally Invasive Surgery in Advanced and Recurrent Ovarian Cancer: Current Evidence and Future Directions

Abstract

Purpose of review:

The use of minimally invasive surgery (MIS) in advanced ovarian cancer management following neoadjuvant chemotherapy yields potential benefits in patient recovery and quality of life compared with traditional open surgery. MIS techniques, including robot-assisted procedures, have been increasingly utilized in recent years despite ongoing debates about their oncologic safety.

Recent findings:

Recent prospective and retrospective studies indicate that MIS for interval debulking after neoadjuvant chemotherapy can achieve similar cytoreductive outcomes (no visible residual disease, CC-0) to laparotomy in carefully selected patients. Key reported advantages include reduced perioperative morbidity, lower blood loss, and shorter hospital stays. Nonetheless, current data are limited by patient selection bias, power of the studies to detect differences, and concerns about accurately detecting small-volume disease laparoscopically. Ongoing randomized controlled trials, such as the LANCE trial, are expected to provide robust evidence to clarify oncologic outcomes of MIS. Additionally, early studies indicate MIS might be feasible for selected cases of recurrent ovarian cancer.

Summary:

MIS is emerging as a viable and potentially advantageous alternative to open surgery for advanced ovarian cancer after neoadjuvant chemotherapy, provided careful patient selection and surgical expertise. Definitive conclusions about long-term oncologic outcomes and recurrence require results from randomized clinical trials.

Introduction

Epithelial ovarian cancer (EOC) is associated with the highest mortality rate among gynecological tumors.¹ Most patients are diagnosed at an advanced stage, marked by widespread tumor within the abdominal cavity. Surgical cytoreduction combined with platinum-based chemotherapy has long been the cornerstone of management, historically requiring extensive open surgery.² In recent years, however, minimally invasive surgery (MIS) techniques, including both conventional laparoscopy and robot-assisted surgery, have been investigated as less invasive alternatives for cytoreduction. Early feasibility studies and retrospective series have suggested that MIS can achieve high rates of complete resection with acceptable oncologic outcomes in carefully selected patients.^3,4 Nevertheless, the role of MIS in advanced ovarian cancer, including its application in recurrent disease, remains controversial and has not yet been universally adopted in international guidelines.⁵ The objective of this review is to examine the current evidence on MIS in advanced-stage ovarian cancer and ovarian cancer recurrences, highlighting its potential advantages, its limitations, and the context of evolving treatment strategies.

Background

EOC is the leading cause of gynecologic cancer death in Western countries, and the majority of patients worldwide present at an advanced stage (International Federation of Gynecology and Obstetrics [FIGO] stage III or IV), which contributes to the high mortality associated with this disease. Importantly, achieving complete resection of all visible tumor deposits—known as CC-0—is the strongest predictor of improved overall and progression-free survival.^5,6

For many years, primary debulking surgery (PDS) via laparotomy followed by chemotherapy was the standard treatment for advanced ovarian cancer.⁷ This approach, aiming to remove as much tumor burden as possible up front, often requires extensive surgeries that might include multiorgan resection and carry substantial morbidity. Such extensive procedures may hinder timely administration of chemotherapy, lead to prolonged length of stay and readmission, and decrease survival.^8,9 These limitations led to the exploration of neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) as an alternative, particularly for patients with very bulky disease or poor surgical candidacy. Landmark randomized trials^8–11 demonstrated that NACT followed by IDS can achieve surgical and survival outcomes similar to those of upfront debulking while significantly reducing surgical morbidity and improving quality of life.

Role of MIS in interval debulking for advanced ovarian cancer

With the growing adoption of NACT for EOC,¹² defining the optimal surgical approach for IDS has become increasingly important. In this context, the use of MIS for IDS has gained traction as a means to further reduce perioperative morbidity. In the United States, the application of MIS for IDS rose from 20.3% of patients treated for advanced-stage EOC in 2013 to 29.11% by 2020 (Figure 1). Patients who have a robust response to NACT may have little or no measurable disease at the time of IDS; in these patients, a MIS approach may achieve complete cytoreduction. However, the promising advantages of MIS and optimal surgical outcomes are contingent upon meticulous patient selection and preoperative assessment.

Figure 1.

Trends in the use of minimally invasive surgery and open approaches for interval debulking surgery for patients with advanced-stage epithelial ovarian cancer from 2010 to 2020. Data from the National Cancer Database.

Feasibility and selection criteria

Selecting appropriate candidates is crucial for successful MIS. Five prospective^3,4,13–15 studies have evaluated MIS for IDS after NACT, all sharing core eligibility requirements. These include advanced-stage EOC (FIGO IIIC–IV), a demonstrable response to platinum-based NACT, a good performance status, and tumor characteristics indicating that laparoscopic or robotic cytoreduction is technically feasible. The National Comprehensive Cancer Network (NCCN) guidelines endorse MIS as an approach for IDS in “select patients”.⁶

The studies vary in design and scale. The largest ones, namely the Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy (LANCE)³ pilot trial (100 patients), CILOVE¹³ (48 patients) and MISSION¹⁵ (52 patients), were multicenter trials, whereas MIRRORS⁴ (23 patients), and a study by Favero et al.¹⁴ (21 patients) were conducted in single-center settings. Selection thresholds also differed. For instance, MIRRORS⁴ required a pelvic mass of ≤8 cm, whereas CILOVE¹³ set a cutoff of <10 cm and excluded supramesocolic disease on imaging. In the MISSION study,¹⁵ a clinical complete response was required, though patients with a partial radiologic response were still eligible if CA-125 levels had normalized. Similarly, the LANCE pilot study³ mandated normal CA-125 levels as a prerequisite for inclusion. LANCE³ limited NACT to 3–4 cycles, whereas Favero et al.¹⁴ used 6 consecutive cycles—considered equally effective while allowing additional time for surgical planning and tumor downstaging.

Preoperative imaging with contrast-enhanced computed tomography is routinely used to assess residual tumor burden following NACT. Radiologic evaluation helps determine whether disease is confined mainly to the pelvis or lower abdomen, with limited upper abdominal involvement, meaning IDS might be feasible. However, imaging may underestimate the true extent of disease; hence, adjunct diagnostic laparoscopy can confirm resectability. Indeed, CILOVE,¹³ MIRRORS,⁴ and MISSION¹⁵ proposed an initial laparoscopic assessment to confirm feasibility before proceeding with MIS.

Feasibility is typically defined by low conversion rates, from 0%^4,14,15 to 9.4%,¹³ and a high proportion of complete or optimal cytoreduction and acceptable morbidity. In the LANCE pilot trial,³ a conversion rate of up to 25% was considered acceptable, and the authors reported 12.5%. Although each study had a relatively small patient population, these prospective data collectively suggest that with careful patient selection, favoring those demonstrating a strong response to NACT and limited disease outside the pelvis, MIS for IDS appears both feasible and safe. Retrospective analyses offer additional perspectives, with conversion rates were generally low, typically 3% to 17%, reinforcing the practical viability of MIS (table 1)

Table 1.

Comparison of Minimally Invasive Surgery vs. Laparotomy for Interval Debulking Surgery in Advanced Ovarian Cancer

First author (year)	Design & sample	Cytoreduction	Operative outcomes	Oncologic outcomes
Favero et al. (2015)14	MIS: 10 patients (prospective) LPT: 11 patients (retrospective)	MIS: CC-0 100% LPT: CC-0 100%	EBL (mean): MIS 180 mL (90–320), LPT not reported. LOS: MIS 3.6 days (2–12), LPT 5.4 days​ (3–14) OR time (mean): MIS 292 min, LPT 264 min (192–410) Conversion rate: 0% Complications: MIS: 2 patients with grade ≥2 complications	OS (%): MIS 20%, LPT 0% (P=0.086)​ Recurrence: MIS 80%, LPT 88%​ Follow-up: MIS 20 mo, LPT 36​ mo
Aletti et al. (2016) 25	MIS: 30 patients (prospective) LPT: 65 patients (retrospective) Matched analysis	MIS: CC-0 in 29 (96.6%), optimal in 1 (3.4%) LPT: CC-0 in 62 (95.4%), optimal in 3 (4.6%)	EBL (median): MIS 100 mL (50–200), LPT 200 mL (100–400 L); p = 0.047 LOS (median): MIS 2 days (2–3) / LPT 4 days (3-8); p = 0.032 OR time (median): MIS 285 min (124–418), LPT 180 min (120–450); p = 0.025 Conversions: Not reported Complications: No early complications in MIS, 2 mild grade 2 complications	PFS: MIS 18 mo, LPT 12 mo (P=0.027); adjusted multivariate analysis showed no differences (P=0.48) OS: Not reported Recurrence: Not reported Follow-up: 28 mo
Liang et al.(2017) 24	MIS: 64 patients LPT: 68 patients Retrospective	MIS: CC-0 in 55 (85.9%), <1 cm in 6 (9.4%) LPT: CC-0 in 46 (67.6%), <1 cm in 6 (8.8%) P=0.008	EBL(mean): MIS 232.2 ± 295.0 mL, LPT 769.6 ± 613.2 mL (P<0.001) LOS (mean): MIS not reported, LPT not reported OR time(mean): MIS 304.5 ± 111.7 min, LPT 389.0 ± 117.4 min (P<0.001) Conversions: 3.1% Complications: Intra-operative: MIS n=3 (4.7%), LPT n=4 (5.9%); post-operative: MIS n=5 (7.8%), LPT n=11 (16.2%)	PFS: 3-year, MIS 55.5%, LPT 33.3%. No significant difference OS: 3-year, MIS 88.7%, LPT 83.7%. No significant difference Recurrence: Not reported Follow-up: Median 18 mo (no significant difference between groups)
Melamed et al. (2017) 17	MIS: 450 patients LPT: 2,621 patients Retrospective	MIS: CC-0 in 130 (46.9%), <1 cm in 90 (32.5%) LPT: CC-0 in 789 (49.5%), <1 cm in 445 (27.9%) (P=0.29)	EBL: Not reported LOS (median): MIS 4 days (2–6), LPT 5 days (4–7) (P<0.001) OR time: Not reported Conversions: 20% (traditional laparoscopy), 5% (robotic) (P<0.001) Complications: Not reported	PFS: Not reported OS: 3-year survival: MIS 47.5%, LPT 52.6% (P=0.12) Recurrence: MIS 80%; LPT 88% (P=0.086) Follow-up: median 32.0mo (95% CI 31.2–33.0)
Brown et al. (2018) 21	MIS: 53 patients (retrospective) LPT: 104 patients Retrospective	MIS: CC-0 in 32 (60.4%), <1 cm in 19 (35.9%) LPT: CC-0 in 44 (42.3%), <1 cm in 42 (40.4%) (P=.02)	EBL(mean): MIS 156 mL (±151), LPT 278 mL (±277) (P<0.001) LOS (mean): MIS 3.0 days (±2.6), LPT 5.7 days (±2.8) (P<0.001) OR time (mean): MIS 171 min (±47), LPT 150 min (±55) (P=0.007) Conversion rate: 17% (MIS to LPT) Complications: Intra-operative: MIS n=1 (1.9%), LPT n=3 (2.9%); post-operative: MIS n=22 (41.5%), LPT n=49 (47.1%) (P=0.45)	PFS: MIS 27 mo, LPT 29 mo (P=0.45) OS: MIS 37, LPT 35 (P=0.74) Recurrence: Not reported Follow-up: Median 15 mo
Abitbol et al. (2019) 22	Robotic era (LPT + robotics): 91 patients Pre-robotic era (LPT only): 22 patients Retrospective	MIS: CC-0 in 47 (82.5%), <1 cm in 10 (17.5%) LPT (pre-robotic era): CC-0 in 9 (40.9%), <1 cm in 11 (50%)	EBL(mean): MIS 135 mL (mean), LPT 505 mL (mean) in pre-robotic era LOS (mean): MIS 1 day (1–17), LPT 6 days (4–27) in pre-robotic era OR time (mean): MIS 312 min (mean), LPT 213 min (mean) in pre-robotic era Conversion: n=6 (10.5%) Complications: No significant difference (P>0.05)	PFS: MIS 20.6 ± 2.4 mo, LPT 11.9 mo (pre-robotic era), 13.9 mo (laparotomy during robotic era) (P=0.005) OS: MIS 47.2 ± 9.8 mo, LPT 37.9 mo (pre-robotic era), 37.8 mo (laparotomy during robotic era) (P=0.04) Recurrence: Pre-robotic era: 19 (86%), robotic era: 73 (80%) Follow-up: Median 41 mo (6–86)​
Persenaire et al. (2021) 18	MIS: 1372 patients LPT: 6713 patients Retrospective	MIS: CC-0: 329 (37.3%), optimal: 264 (29.9%) LPT: CC-0: 1567 (35.5%), optimal: 1370 (31.0%)	EBL: Not reported LOS (median): MIS 3 days / LPT 5 days (p<0.01) OR time: Not reported Conversion rate: 2.3% Complications: Not reported Others: Lower frequency of bowel resections in MIS (16% vs. 24.6% in LPT) 30-day readmission: Similar in both groups (3%)	Median OS: MIS 36.5 vs. LPT 35.2 months (HR 0.94, 95% CI 0.86–1.04) Multivariable-adjusted OS: No significant difference in OS Recurrence: Not reported
Zhang et al. (2021) 23	MIS (robotic): 43 patients LPT: 50 patients Retrospective, single-institution study	MIS: CC-0: in 63% LPT: CC-0 in 52% (p=0.4)	EBL: MIS 98.7 mL vs. LPT 372.9 mL (P<0.001) LOS: MIS 1.6 days vs. LPT 4.7 days (P<0.001) OR time: MIS 250.8 min vs. LPT 239.4 min (P=0.3) Conversion rate: 5 patients converted from MIS (analyzed via intention-to-treat) 30-day complication rate: MIS 18% vs. LPT 47% (P=0.005)	PFS: MIS 16.7 mo vs. LPT 15.4 mo (P=0.7) OS: MIS 35.6 mo vs. LPT 38.2 mo (P=0.7) Follow-up: Median ~27–32 mo
Lecointre et al. (2022) 26	MIS: 37 patients LPT: 40 patients Retrospective propensity-matched (25 patients per group)	MIS: CC-0 in 100% LPT: CC-0 in 100%	EBL (mean): Not reported LOS (mean): MIS 7.6 days, LPT 12.1 days (P<0.001)​ OR time (mean): Not reported Conversion rate: Not applicable (100% CC-0 in both groups)​ Complications: MIS n=6, LPT n=17 (P=0.01)​	OS: MIS 23.1 mo, LPT 26.3 mo (P=0.17)​ After matching: HR 0.45 [95% CI 0.19–0.95], p = 0.04 PFS: MIS 14.8 mo, LPT 12.0 mo (P=0.057)​ After matching: HR 0.71 (95% CI 0.27–1.88, P=0.49) Recurrence: Not explicitly reported Follow-up: Not explicitly reported
Jorgensen et al. (2023) 19	MIS: 2021 patients LPT: 5876 patients Matched analysis from National Cancer Database	MIS: CC-0 in 43.2% Residual disease present in 23.9% LPT: CC-0 in 38.6% Residual disease present in 26.7%	EBL: Not reported LOS (median): MIS 3 days (median), LPT 5 days (median) (P<0.01)​ OR time: Not reported Conversion rate: 10.3% (208/2021)​ Complications: Not reported	OS: MIS 46.7 mo, LPT 41.0 mo (HR 0.86, 95% CI 0.79–0.94)​; OS (adjusted): HR 0.45 (95% CI 0.19–0.95, P=0.04) PFS: Not reported Recurrence: Not reported Follow-up: Not reported
Rauh-Hain et al. (2024) 3	MIS: 49 patients LPT: 51 patients All received neoadjuvant chemotherapy Randomized controlled trial (pilot phase)	MIS: CC-0 in 88% (42/48) LPT: CC-0 in 83% (39/47)	EBL(median): MIS 100 mL (IQR 50–250), LPT 200 mL (IQR 100–400) (P=0.03)​ LOS (median): MIS 1 day (IQR 0–4), LPT 4 days (IQR 3–6) (P<0.01)​ OR time: Not reported Conversion rate: 12.5% (6/48)​ Complications: MIS 8% (4/48), LPT 26% (12/47) (P=0.04)​	Not yet available (awaiting full trial results)

Operative outcomes: When the study does not indicate the specific statistical measure used, no assumption is made as to whether the values represent means or medians

Follow-up was the median follow-up value.

CC-O, no visible residual disease; EBL, estimated blood loss; HR, hazard ratio; IQR, interquartile range; LOS, length of hospital stay; LPT, laparotomy or open surgery; MIS, minimally invasive surgery; OR, operating room; OS, overall survival; PFS, progression-free survival

Oncologic outcomes

A central concern regarding MIS for IDS in advanced EOC is whether it achieves oncologic outcomes similar to those of an open approach. Despite the increasing popularity of MIS, high-grade evidence remains limited, primarily due to reliance on non-randomized studies. Observational data, including national database analyses,^16–18 indicate similar overall survival (OS) outcomes after adjustment for key clinical variables. Specifically, Jorgensen et al.¹⁸ demonstrated improved 5-year survival probabilities for MIS compared with laparotomy (38.3% vs. 34.8%; hazard ratio [HR] 0.86, 95% CI 0.79–0.94). However, the study’s ability to estimate survival at baseline, before surgery, was limited by a lack of data on functional status and disease burden, and information on residual disease status was missing, which may affect the interpretation of results.

A recent systematic review and meta-analysis¹⁹ focusing on patients undergoing IDS found no significant difference in OS between MIS and laparotomy (HR 0.80, 95% CI 0.61–1.05, P=0.11), although MIS showed a significant improvement in progression-free survival (PFS) (HR 0.67, 95% CI 0.48–0.94, P=0.02). This systematic review highlighted the heterogeneity and predominantly retrospective nature of the included studies, introducing potential selection biases and confounders.

Several retrospective studies^20–23 have compared MIS versus laparotomy for interval debulking in advanced ovarian cancer, generally suggesting that both approaches yield similar oncologic outcomes when patients are appropriately selected (Table 1). In cohorts studied by Brown et al.²⁰ and Zhang et al.,²² no significant difference in PFS was detected between MIS and laparotomy, despite median PFS values exceeding 15 months in both arms, increasing the likelihood of observing a difference if present. However, Abitbol et al.²¹ showed that while PFS did not significantly differ between the pre-robotic era (laparotomy only) and the post-robotic era (laparotomy combined with robotics), patients treated with MIS within the post-robotic era achieved a significant PFS benefit. Conversely, Liang et al.²³ found no significant difference in PFS between approaches, although both groups achieved median PFS exceeding 18 months. Similarly, in a retrospective, matched study including 65 laparotomies and 50 MIS cases, Alletti et al.²⁴ reported that after adjustment for confounding factors, the surgical approach was not independently associated with PFS (P=0.48). More recently, Lecointre et al.²⁵ published a propensity-matched cohort study (n=25 per group) in which both groups achieved 100% complete cytoreduction and showed no significant difference in median PFS (14.8 vs. 12.0 months, P=0.057), and OS (26.3 vs. 23.1 months, P=0.17).

Overall, the majority of comparative studies underscore that as long as complete cytoreduction is achieved, neither surgical approach produces a marked oncologic benefit or detriment. Nonetheless, many of these studies carry significant limitations. Centers may preferentially select MIS for patients with lower tumor burden or better response to chemotherapy, introducing selection bias. Additionally, most of these studies were observational and carried a high risk of bias. Few accounted for potential confounders, and those that did were unlikely to have addressed all relevant variables. Furthermore, many were underpowered to detect meaningful clinical differences.^19,26

Prospective trials¹³⁴¹⁴ report preliminary survival outcomes for MIS that are generally similar to those of historical laparotomy cohorts. Notably, CILOVE reported favorable 12-month PFS rates (87.5%) while MIRRORS similarly showed promising early survival data. Conversely, Favero et al.¹⁴ highlighted inferior oncologic outcomes, including a potentially higher cancer-related mortality in the MIS cohort, although the study was limited by the small sample size and was observational.

Perioperative outcomes

Assessing perioperative complications is essential in evaluating MIS versus laparotomy for IDS in patients with advanced-stage EOC, as these outcomes critically influence patient safety, quality of care, and healthcare resource utilization. Current evidence indicates generally similar or potentially improved perioperative outcomes for MIS compared to laparotomy, although methodological biases and heterogeneity among studies limit the generalizability of these findings. Prospective single-arm trials designed to explore perioperative safety and feasibility,¹³ alongside comparative prospective trials like LANCE and MIRRORS,^3,4 consistently report favorable outcomes of MIS. Most notably, these trials demonstrate shorter hospital stays (2–4 days), reduced estimated blood loss (100–180 mL), and acceptable complication rates (grade ≥2 complication rates of 0%–8%), underscoring further practical benefits of MIS. Notably, CILOVE¹³ documented minimal serious postoperative complications, with no grade ≥2 events, and a low intraoperative complication rate of 2%. Similarly, MIRRORS⁴ highlighted the low complication rates of robotic IDS, reporting minimal postoperative morbidity and reinforcing the safety profile of MIS techniques in carefully selected patients.

Retrospective analyses provide complementary insights, typically reflecting real-world practice variability (Table 1). Across multiple studies, MIS has been associated with favorable operative profiles, including shorter hospital stays (1–4 days for MIS vs. 4–12 days for laparotomy) and reduced estimated blood loss (99–232 mL for MIS vs. 278–770 mL for laparotomy). Intraoperative complication rates were typically low, generally under 5%, while postoperative complication rates ranged broadly from 7.8% to 41.5% for MIS versus 16.2% to 47% for laparotomy. Nevertheless, again, these findings are limited by their observational nature, the potential for confounding factors, and varying degrees of extension of disease at diagnosis.

Overall, except for longer operative times, evidence collectively suggests that MIS for IDS in advanced-stage EOC can offer favorable perioperative outcomes, including reduced blood loss, shorter hospital stays, and acceptable complication rates compared to traditional laparotomy. However, definitive confirmation of these findings requires randomized controlled trials to provide robust comparative evidence.

Controversies and technical challenges

Despite its promising advantages, several controversies and technical challenges persist with MIS for IDS. One concern is that the limited tactile feedback inherent to laparoscopy may lead to underestimation of disease extent, potentially resulting in incomplete cytoreduction. Small peritoneal implants, particularly in the subdiaphragmatic or mesenteric regions, may be missed during a minimally invasive exploration. Additionally, complex procedures such as diaphragm stripping, splenectomy, or bowel resections via MIS remain technically demanding and are typically limited to specialized, high-volume centers. Furthermore, the learning curve associated with advanced MIS techniques is steep, and inter-operator variability remains a significant factor. Some early series¹⁴ reported higher complication rates during the initial adoption phase, although outcomes improved with experience. Lastly, although port-site metastases are low ²⁷,they represent an additional oncologic risk to monitor and warrant preventive measures. Overall, while MIS offers distinct perioperative benefits, its use for IDS should be limited to selected patients and performed by surgeons with proven expertise in advanced MIS. Certain intraoperative precautions should be standard practice to reduce the risk of tumor dissemination, including the routine use of specimen retrieval bags (i.e Endo Bags), minimizing surgical specimen manipulation, and ensuring controlled exsufflation.

The use of MIS in primary debulking surgery remains controversial due to limited and methodologically flawed evidence. Few studies have assessed long-term outcomes beyond 5 years, and a recent systematic review found a lack of high-quality data to accurately determine its risks and benefits in advanced EOC.¹⁹ A meta-analysis by Nezhad et al.²⁸ suggested similar operative times, blood loss, and hospital stays between MIS and laparotomy, along with slightly improved rates of optimal and complete cytoreduction for MIS. However, these findings must be cautiously interpreted, given substantial heterogeneity, small sample sizes, and inherent selection biases across studies. Overall, the role of MIS in primary cytoreduction remains controversial and considerably more complex compared to interval or secondary debulking settings, emphasizing the need for rigorous, adequately powered randomized studies to establish clear clinical guidelines.

Role of minimally invasive surgery in secondary cytoreductive surgery

The role of secondary cytoreductive surgery in recurrent ovarian cancer remains an area of active investigation, with three landmark randomized trials yielding conflicting results. The GOG-213 trial²⁹ randomized 485 patients (240 to secondary cytoreduction before chemotherapy and 245 to chemotherapy alone). With a median follow-up of 48.1 months, the trial reported no statistically significant OS advantage with secondary surgery compared to chemotherapy alone (HR for death, 1.29, 95% CI 0.97–1.72, p=0.08). In contrast, the DESKTOP III trial³⁰, involving 407 randomized patients (206 assigned to secondary cytoreduction plus chemotherapy, and 201 to chemotherapy alone), reported a significantly higher complete cytoreduction rate of 75%. The median OS was significantly improved in the surgery group (53.7 months) compared to chemotherapy alone (46 months), with an HR for death of 0.75 (95% CI 0.59–0.96, P=0.02). Complementing these findings, the SOC-1 trial³¹ demonstrated a marked PFS benefit from the surgery, with a median PFS of 17.4 months versus 11.9 months without surgery (HR 0.58, 95% CI 0.45–0.74, P<0.0001). However, OS analysis³² reported no differences in OS, with a median OS of 58.1 months for the surgery group versus 52.1 months for the no-surgery group (HR 0.80, 95% CI 0.61–1.05, P=0.11). This narrative convergence underscores that while these trials support the role of secondary cytoreduction in delaying disease progression through complete resection, the impact on OS may be influenced by factors such as subsequent treatments and study design nuances.

Those trials exclusively employed open surgical approaches. However, retrospective studies have also investigated MIS as a potential alternative for secondary cytoreduction in carefully selected patients, particularly those presenting single or oligometastatic disease or isolated nodal recurrences. Conte et al.³³ conducted a propensity-matched cohort analysis of 276 patients, rigorously selected via preoperative positron emission tomography/computed tomography and diagnostic laparoscopy, achieving a complete cytoreduction rate of 100% in the MIS group versus 92.3% in the open surgery group (P=0.08). The study demonstrated significantly lower perioperative morbidity with MIS without compromising oncologic outcomes. Smaller retrospective studies further support these findings. For instance, Eriksson et al.,³⁴ with a cohort of 86 patients (39 with MIS, 47 with laparotomy), reported similar complete cytoreduction rates (MIS: 95% vs. laparotomy: 93%, P=1.0) and similar 2-year PFS (MIS: 56.1% vs. laparotomy: 63.5%, P=1.0) and OS (MIS: 92.2% vs. laparotomy: 81.4%, P=0.7). Magrina et al.,³⁵ evaluating 52 patients (19 MIS, 33 laparotomy), also found similar complete cytoreduction rates (MIS: 88.9%, laparotomy: 72.7%, robot-assisted: 70%, P=0.66), PFS at 3 years (MIS: 22.9%, laparotomy: 33.1%, robot-assisted: 43.8%, P=0.95), and OS (MIS: 66.7%, laparotomy: 48.4%, robot-assisted: 85.7%, P=0.18). Similarly, Fagotti et al,.³⁶ assessing a smaller matched cohort of 22 patients (11 MIS, 11 laparotomy), achieved complete cytoreduction in all patients in both groups, with significantly reduced median operative times (125 min for MIS vs. 295 min for laparotomy, P=0.001), lower median blood loss (MIS: 50 mL vs. laparotomy: 500 mL, P=0.025), and shorter median hospital stays (MIS: 4 days vs. laparotomy: 8 days, P=0.002). The NCCN guidelines⁶ permit secondary cytoreduction using either open or MIS approaches. Using validated scoring methods to assess patient suitability for secondary cytoreduction is recommended.

Despite promising perioperative and oncologic outcomes, these retrospective analyses have significant methodological limitations. Selection bias is a major concern, as studies like those by Conte et al. and Fagotti et al. employ strict preoperative criteria, including advanced imaging and diagnostic laparoscopy, which likely increase success rates and limit generalizability. Small sample sizes and inadequate matching methods introduce further confounding. Additionally, key oncologic details—such as prior chemotherapy regimens, use of targeted therapies like PARP inhibitors or bevacizumab, and recurrence treatment protocols—are often underreported, complicating outcome interpretation.

While preliminary data suggest MIS is a feasible, safe, and effective option for select recurrent ovarian cancer patients, definitive conclusions remain elusive. Prospective randomized trials would be ideal but are impractical due to the need for large sample sizes, highly selected patient populations, and complex stratification. As a result, clinicians and researchers will likely rely on retrospective feasibility studies and large, multicenter prospective registries.

Ongoing trials and future directions

The ongoing LANCE trial³⁷ is a rigorously designed study that aims to provide definitive evidence on the optimal surgical approach for women with EOC after NACT. This international, prospective, randomized, multicenter, non-inferiority study aims to compare minimally invasive IDS (experimental arm) with open IDS (control arm) among women with EOC that has responded to NACT. This trial is especially relevant given the recent concerns about the oncologic safety of MIS in cervical cancer, where MIS hysterectomy, previously standard, was found to be inferior to open radical hysterectomy.³⁸

Additionally, MIRRORS⁴ is a planned randomized controlled trial assessing the feasibility and oncologic safety of robotic IDS in advanced ovarian cancer. Building on the findings of the MIRRORS cohort study, this trial will compare robotic surgery with standard open IDS to determine non-inferiority in survival, morbidity, and quality of life outcomes. If robotic MIS for IDS is proven safe and effective, such findings could further expand the role of MIS in ovarian cancer treatment.

Looking ahead, another major component of personalized care involves comprehensive molecular profiling, particularly BRCA testing. High-grade serous ovarian carcinomas often harbor BRCA mutations, with germline alterations identified in approximately 13%–15% of patients and somatic mutations in an additional 5%–7%. This molecular signature correlates with enhanced responses to platinum-based chemotherapy and PARP inhibitors and may also predict improved surgical outcomes. As a result, routine BRCA testing is now recommended as an integral part of the diagnostic workup.⁵ Future directions in ovarian cancer management will likely combine refined surgical selection strategies—like those studied in LANCE—with routine genetic testing and targeted systemic therapies, offering an increasingly individualized approach to patient care.

Conclusion

MIS for IDS after NACT has shown promise for select patients with advanced EOC, offering similar oncologic outcomes to laparotomy while reducing perioperative morbidity and hospital stays. However, concerns remain regarding selection bias, limitations in assessing disease extent laparoscopically, and variability in surgeon expertise. Ongoing randomized trials, such as LANCE, will help define the oncologic safety of and refine clinical guidelines for this approach. Additionally, early data suggest MIS may be feasible for secondary cytoreductive surgery in recurrent ovarian cancer, but stronger evidence is needed to confirm oncologic safety and ensure appropriate patient selection.

Key Points:

• Minimally invasive surgery (MIS) after neoadjuvant chemotherapy offers reduced morbidity and shorter hospital stays compared to laparotomy.

• Careful patient selection and surgeon expertise are critical to achieving optimal outcomes in MIS.

• Preliminary evidence suggests similar recurrence outcomes between MIS and laparotomy.

• Ongoing randomized trials, such as LANCE, will clarify the oncologic safety of MIS for interval cytoreduction.