Imaging methods often cannot differentiate between the different kinds of adnexal masses on their own, when it comes to functional and benign variants. Accurately predicting the presence of ovarian cancer and the need for surgery can both be improved with laparoscopy. This method also helps in making a correct diagnosis before surgery. Laparoscopy is an improved technique as it helps reduce the need for individuals to undergo unnecessary surgery to treat functional and benign ovarian cysts (25,26). A histology examination of the tumor and its implants typically offer additional diagnostic insights, along with information regarding the stage of disease. Laparoscopy facilitates the sampling of purulent peritoneal effusion for culture testing, which aids in the identification of any accompanying infection and in determining the appropriate surgical approach (20).

In the context of malignant diseases, prioritizing the complete removal of the primary tumor is key in ovarian cancer as well. The primary objective of oncologists and gynecologists is to ensure the safety of the patient; therefore, it is essential to maintain a pathway for the potential conversion of laparoscopy to laparotomy at any given time. Furthermore, depending on the experience of the surgical oncologist, MITs such as laparoscopy can provide patients with adnexal masses of unclear origin the same diagnostic and therapeutic surgical staging benefits as laparotomy (21). Furthermore, the prevention of notable surgical procedures and complications can lead to a more efficient recovery process for the patient. These factors enhance the quality of life (QoL) and potentially the self-esteem of patients while reducing their costs (21,27,28).

In EOC surgery, the robotic system enhances precision and dexterity of the surgeon, enabling fine dissection and removal of primary tumors, targeted omentectomy and systematic lymphadenectomy through small ports with three-dimensional magnified visualization (29). Robotic-assisted surgery is particularly crucial for patients with cardiovascular, hepatic, renal or pulmonary comorbidities, as it minimizes physiological stress by reducing intraoperative blood loss, shortening operative time and maintaining stable intra-abdominal pressures, thereby lowering cardiopulmonary complication rates. In women aged 18–40 years who desire fertility preservation, combining laparoscopy with robotic precision enables accurate tumor resection, targeted omentectomy and unilateral salpingo-oophorectomy while sparing the contralateral ovary (29). Multiple retrospective series have demonstrated that robotic cytoreduction reduces hospital stays to an average of 2–3 days and decreases 90-day morbidity compared with open surgery, driving its increasing adoption among gynecological oncologists (21,28,30,31).

A 2-year retrospective observational study was conducted, analyzing data on women diagnosed with ovarian cancer and compared outcomes according to their surgical methods (29,30). Robot-assisted surgery enables precise pelvic and para-aortic lymphadenectomy, including dissection of nodal stations enriched with hematopoietic progenitor cell niches, thereby improving staging accuracy while minimizing collateral tissue trauma. This allows the provision of gonadotoxic treatments to these patients, which protects their ability to have children. The robot-assisted surgical approach has been employed to perform systematic pelvic and para-aortic lymphadenectomy, enabling accurate staging of ovarian cancer and facilitating evaluation of the therapeutic impact of varying lymph node harvests (31). Robotic surgery methods may help identify high-risk patients who can have a full lymphadenectomy and still receive fertility-preserving treatment. The growing adoption of MITs in ovarian cancer surgery highlights various benefits, including enhanced patient satisfaction and potential cost savings associated with these approaches.

Targeted therapies are fundamental in ovarian cancer management as they are designed to interfere with specific molecular pathways that cancer cells rely on for growth, survival and proliferation, distinguishing them from traditional chemotherapy agents such as carboplatin, paclitaxel and doxorubicin, which broadly target all rapidly dividing cells. Unlike conventional chemotherapy, which causes damage to both malignant and normal cells leading to significant side effects such as neutropenia, alopecia, mucositis and fatigue, targeted therapies such as PARP inhibitors (including olaparib and rucaparib), anti-angiogenic agents (including bevacizumab) and folate receptor α inhibitors (including mirvetuximab), specifically attack pathways activated only in cancer cells, resulting in fewer off-target effects. These therapies work by inducing apoptosis through disruption of cancer-specific signaling pathways, including homologous recombination repair pathways and tumor angiogenesis processes, which suppress tumor growth and promote cancer cell death. Furthermore, predictive biomarkers such as BRCA mutations and HRD status enable clinicians to identify patients who are most likely to benefit from these targeted treatments, providing a personalized approach that enhances efficacy (35,43–45).

Nonetheless, the emergence of drug resistance presents a notable limitation. A potentially more effective strategy may involve a combination therapy utilizing ≥2 targeted agents or integrating chemotherapy with hormone therapy alongside a targeted agent to enhance sensitivities (46). The foundation of these approaches relies on current understanding of the molecular pathways that serve a role in the development and progression of cancer. In the past decade, research on EOC has highlighted mutations or amplifications in specific genes that indicate the involvement of pathways associated with DNA damage repair, apoptosis, cell cycle control and anti-angiogenesis. The present review underscores the necessity for innovative pharmaceuticals and the initiation of clinical trials to explore therapeutic alternatives.

In recent years, PARP inhibitors have emerged as a prominent class of targeted therapies in EOC (32,33,47). These agents act by disrupting the DNA repair process, specifically, the repair of single-strand DNA breaks. When PARP is inhibited, these breaks evolve into double-strand DNA damage, which cannot be effectively repaired in cancer cells harboring BRCA1/2 mutations, which leads to cell death via synthetic lethality (37,46,48). Currently, three PARP inhibitors, olaparib, rucaparib and niraparib, are approved by the Food and Drug Administration for ovarian cancer treatment, based on a number of pivotal trials (40,41,49).

For instance, the SOLO-1 trial demonstrated a notable increase in PFS from 13.8 to 56 months in newly diagnosed patients with BRCA-mutated EOC receiving olaparib as maintenance therapy [Hazard ratio (HR), 0.30; P<0.001] (40). The PRIMA trial extended this benefit to a broader population, which demonstrated improved PFS from 8.2 to 13.8 months with niraparib in both BRCA and non-BRCA advanced cases (HR, 0.62; P<0.001) (41). In recurrent BRCA-mutated EOC, the ARIEL3 trial confirmed the efficacy of rucaparib, with PFS increasing from 5.4 to 10.8 months (HR, 0.36; P<0.0001) (49). The VELIA trial assessed veliparib added to first-line chemotherapy and as maintenance, which reported an increase in PFS from 17.3 to 23.5 months (HR, 0.68; P<0.001), which supports the role of PARP inhibitors in newly diagnosed EOC (50). Notably, the PAOLA-1 trial evaluated the combination of olaparib with bevacizumab in HRD-positive patients, which demonstrated improved PFS from 16.6 to 22.1 months (HR, 0.59; P<0.001), which suggested potential synergy between DNA repair inhibition and anti-angiogenic therapy (35). Together, these trials establish the clinical efficacy of PARP inhibitors across different settings: BRCA-mutated, HRD-positive and BRCA wild-type subpopulations. While resistance mechanisms and optimal combinations remain areas of active research, ongoing research continues to explore the role of PARP inhibitors in frontline and maintenance therapy (Table I). These results have firmly established PARP inhibitors, particularly olaparib and niraparib, as standard of care in maintenance therapy for EOC.

Angiogenesis serves a key role in ovarian cancer progression, which supports tumor growth and metastasis by establishing a dedicated blood supply. Targeting this pathway has yielded promising therapeutic strategies, particularly with bevacizumab, a monoclonal antibody against VEGF and pazopanib, a multi-targeted angiogenesis inhibitor (16,51).

In the GOG-0218 trial, bevacizumab added to standard first-line chemotherapy extended PFS from 10.3 to 14.1 months (HR, 0.717; P<0.001), which highlighted its benefit in newly diagnosed advanced ovarian cancer (16). Similarly, the ICON7 trial demonstrated a modest but notable improvement in PFS (17.3–19 months) in patients receiving bevacizumab with chemotherapy (HR, 0.81; P=0.004) (52). In the recurrent setting, the OCEANS trial confirmed the benefit of bevacizumab in platinum-sensitive relapse, with PFS rising from 8.4 to 12.4 months (HR, 0.484; P<0.0001) (53). For maintenance therapy, the AGO-OVAR16 study evaluated pazopanib and observed a PFS extension from 12.3 to 17.9 months in advanced ovarian cancer (HR, 0.77; P=0.0021) (51).

In recurrent settings, the OCEANS trial demonstrated that adding bevacizumab to chemotherapy improved PFS from 8.4 to 12.4 months (HR, 0.484; P<0.0001) in platinum-sensitive relapses. Similarly, the AGO-OV/AR16 study demonstrated that pazopanib maintenance extended PFS from 12.3 to 17.9 months in advanced ovarian cancer (HR, 0.77; P=0.0021). Despite these positive results, resistance to anti-angiogenic therapy remains a challenge and future directions may involve biomarker-guided patient selection or combination regimens with immunotherapy or PARP inhibitors (Table I). While bevacizumab is incorporated into standard regimens based on GOG-0218 and ICON7, other agents such as pazopanib warrant further investigation.

TKIs represent a diverse class of targeted agents designed to interfere with signaling pathways that mediate tumor cell proliferation, survival, angiogenesis and invasion (54–56). TKIs block multiple oncogenic signaling cascades that contribute to ovarian cancer growth and spread. By inhibiting the VEGFR and platelet-derived growth factor receptor, TKIs disrupt angiogenesis and stromal support for tumor proliferation, while blockade of fibroblast growth factor receptor signaling further impairs neovascularization and cell survival. In addition, inhibition of the hepatocyte growth factor/c-MET axis reduces tumor cell motility and invasion, and targeting other kinases such as AXL and RET overcome resistance mechanisms and attenuates survival pathways in cancer cells (57–59). Several TKIs have been investigated in ovarian and endometrial cancer types, with growing evidence supporting their utility, especially in combination strategies. For example, anlotinib, a multi-targeted TKI assessed in the ALTER-GO-010 phase II trial for newly diagnosed advanced ovarian cancer. This single-arm study reported a 100% PFS at both 6 and 9 months, with a median PFS of 5.36 months (95% CI, 3.68–7.98), although final PFS was not yet reached due to ongoing follow-up (54,60). The MITO 11 study, while primarily assessing anti-angiogenesis, also demonstrated the efficacy of pazopanib, which possesses TKI activity. Pazopanib combination with paclitaxel yielded notable improvements in PFS in a platinum-resistant/refractory cohort (55). A novel combination of a TKI and immunotherapy was explored in trial NCT03367741, which evaluated cabozantinib plus nivolumab in recurrent endometrial cancer. Patients receiving the combination had a PFS of 5.3 vs. 1.9 months with nivolumab alone (HR, 0.59; P=0.09) (56). Although these trials focused on endometrial compared with ovarian cancer, these findings highlight the expanding landscape of TKI-based combinations in gynecological oncology.

Furthermore, in the NCT03367741 study, the combination of cabozantinib and nivolumab was investigated in recurrent endometrial cancer, which indicated a PFS improvement from 1.9 to 5.3 months (HR, 0.59), which suggests potential synergy between TKIs and immune checkpoint inhibitors, although these findings remain preliminary and warrant further exploration in ovarian cancer (56). Overall, while TKIs alone have demonstrated modest efficacy, their integration into combinatorial regimens, especially with immune checkpoint inhibitors, may offer enhanced therapeutic outcomes. Ongoing trials continue to assess the optimal positioning of TKIs in ovarian cancer treatment, including in front-line, maintenance and recurrent settings (Table I). TKI-based combinations, such as those explored in ALTER-GO-010 and NCT03367741, remain investigational and require validation through larger trials.

Several types of vaccines have been investigated in EOC, most containing proteins or peptides that are associated with ovarian cancer. Examples of tumor-associated antigens targeted in ovarian cancer vaccines include MUC1, cancer-testis antigen NY-ESO-1, WT1, folate receptor α and mesothelin (61). Numerous studies have seen T-cell responses or longer disease stability in patients who are getting treatment; however, not all of these studies demonstrated the same benefits (62–64). The initial vaccine evaluated in EOC and the only vaccine assessed in a randomized phase III trial was canvaxin. Autologous tumor cell lysates were changed to add a novel glycosylation site to the mucin 1 protein, which is a known antigen located in ovarian tumors. The vaccine generated antibody responses in 88% of vaccinated patients and seemed to improve tolerance compared with the chemotherapy recommended by the physician in a selected group of women. Eventually, this trial had to be discontinued because the tumors were not under control (65–67). However, canvaxin was still investigated in other studies as an adjuvant, with and without chemotherapy, specifically in patients with EOC (68,69). Several recent clinical trials have evaluated novel antigen-targeted vaccines in EOC (61). The phase I study of folate receptor-α peptide vaccine in patients with advanced ovarian cancer demonstrated induction of FRα-specific CD8⁺ T-cell responses in 90% of participants and disease stabilization in 40% at 6 months. A multicenter phase II trial of the MUC1-liposomal vaccine tecemotide added to neoadjuvant platinum-taxane chemotherapy reported enhanced MUC1-specific CD4⁺ and CD8⁺ T-cell responses in 75% of patients, with a 12-month PFS of 65% compared with 50% historical controls. These treatments demonstrate the potential to prepare women for subsequent therapy with immune checkpoint inhibitors (61,67).

Adoptive transfer of tumor-infiltrating lymphocytes and engineered CAR-T cells targeting mesothelin, HER2 or folate receptor α have demonstrated potent antigen-specific cytotoxicity and clinical activity in early-phase trials of EOC, especially for antibody-coated T cells, chimeric antigen receptor T cells (CAR-T), specifically chosen tumor-infiltrating lymphocytes or those that have been engineered to express a tumor-specific T-cell receptor (70–72). By using genetic engineering to change the T cells of a patient, CAR-T therapies make it possible for these cells to express specific receptors that help find and kill cancer cells. CAR molecules have an antigen-binding domain that is outside of cells, a transmembrane domain and an intracellular signaling domain that activates more co-stimulatory receptors after interacting with the target epitope (73,74). Therefore, CAR-Ts demonstrate specificity for a certain antigen while also being less dependent on HLA expression. CAR-T therapies have evolved in recent years and gaining attention in the field. The anti-CD19 therapy has demonstrated potential in treating patients with B-cell malignancies (75). Concerning EOC, CAR-T-based approaches have been created to target different antigens associated with tumors, such as mesothelin, HER2 and folate receptor α. These treatment approaches have demonstrated potential in early-stage clinical trials (76–79).

Immune checkpoint inhibitors have transformed the treatment landscape for multiple malignancies, including metastatic melanoma, non-small cell lung cancer and renal cell carcinoma. By blocking receptors such as PD-1 on T cells or ligands like PD-L1 on tumor cells, these agents prevent inhibitory signaling that normally dampens T-cell activation. Specifically, PD-1/PD-L1 blockade restores T-cell receptor signaling, leading to increased proliferation of effector T cells, enhanced cytokine production and sustained antitumor cytotoxicity. The goal of anti-PD-1/PD-L1 therapies was to revive lymphocytes that had been eliminated by advanced tumors. Anti-PD-1/PD-L1 therapies demonstrated efficacy for several types of cancer that exhibited HLA-antigen presentation; therefore, the demonstrating potential for these types of drugs to help treat EOC. The effectiveness of these drugs could be increased by combining them with other treatments, such as VEGF inhibitors, PARP inhibitors or platinum-based chemotherapy (64,80). The efficacy of both anti-PD-1 and anti-PD-L1 antibodies have been assessed in patients with EOC. Anti-PD-1/PD-L1 monotherapy in EOC has produced modest clinical benefits. In the phase II trial of nivolumab in platinum-resistant ovarian cancer, the objective response rate was 15% and the disease control rate (responses plus stable disease ≥6 months) was 45%, with a median PFS of 3.5 months. Similarly, pembrolizumab in the KEYNOTE-100 study achieved an ORR of 8% and a DCR of 34%, with a median PFS of 2.1 months, indicating that while a subset of patients experiences prolonged stabilization, the overall impact on disease control remains limited (81,82). As a stand-alone treatment, PD-L1 blockade has had response rates of <15%. This suggests that blocking the PD-L1/PD-1 interaction may not be enough to activate and grow T cells, unlike what has been reported with anti-CTLA-4 therapies. Consequently, further immunotherapy approaches are currently being investigated (64,80).

Combining targeted therapies with immunotherapy or chemotherapy holds notable potential in improving outcomes for patients with EOC. PARP inhibitors, when combined with immune checkpoint inhibitors, may enhance antitumor immunity by increasing the tumor neoantigen load and modulating the tumor microenvironment (37,83). Similarly, combining anti-angiogenic agents with immunotherapy can normalize tumor vasculature, promoting enhanced immune cell infiltration. However, these combinations present challenges, including increased risk of overlapping toxicities, optimal treatment schedule, dosing strategies and patient selection. Optimal sequencing refers to the strategic order and timing of administering each therapy to maximize synergistic efficacy and minimize cumulative toxicity. In EOC combinations: For PARP inhibitor + ICI: Sequencing may involve giving the PARP inhibitor first to induce DNA damage and neoantigen release, then administering PD-1/PD-L1 blockade at the peak of antigen presentation to reinvigorate T cells. For anti-angiogenic + ICI: VEGF inhibition is often delivered prior to checkpoint blockade to normalize abnormal tumor vasculature and improve effector T-cell infiltration, followed by PD-1/PD-L1 antibodies to sustain the immune response (37,84,85). Furthermore, identifying reliable biomarkers to predict response remains an unmet need (86). Ongoing trials are actively exploring these strategies and future research will be key to refining combination approaches and determining their place in clinical practice (37).

Achieving minimal or no gross residual disease (R0) is critical in advanced ovarian cancer. Recent studies indicate that MIS can attain similar optimal cytoreduction rates as open surgery in selected patients. A 2024 meta-analysis stratified by surgery timing reported no notable difference in optimal debulking rates between MIS and laparotomy for both primary debulking surgery (PDS) and interval debulking surgery (IDS). In interval debulking after NACT, the pooled risk ratio for achieving optimal cytoreduction with MIS was ~1.03 relative to open surgery (95% CI, 0.96–1.11; P=0.05), essentially indicating equivalent success rates. Similarly, the rate of complete gross resection (no macroscopic disease) did not differ between MIS and open approaches (risk ratio, ~1.01; 95% CI, 0.97–1.07) (34). These findings have been similarly reported by other studies (34,42,89); a 2022 systematic review reported no notable disparity in R0 (complete debulking) or R1 (≤1 cm residual) rates between laparoscopic/robotic IDS and open IDS (89).

Individual cohort studies reinforce that well-selected MIS cases can achieve high R0 rates. In the multi-center MISSION trial (2019), which evaluated 127 patients undergoing MIS IDS, 96.1% of patients had no gross residual disease at surgery. The conversion to laparotomy in that series was only ~3.9%, which implied that nearly all intended MIS procedures could be completed with optimal resection (42). Certain single-center studies have reported slightly lower complete resection rates with MIS, but these differences appear to reflect case selection. For example, Pereira et al (90) observed a higher R0 rate in their laparotomy group compared with MIS groups, potentially because surgeons attempted MIS only in cases with smaller tumor burden. Across numerous reports, when MIS was chosen for patients with limited disease distribution or marked chemotherapy response, residual disease outcomes were comparable with to open surgery (34,89).

Long-term survival outcomes (overall survival and PFS) have been a central concern when comparing MIS to open debulking in advanced ovarian cancer. Notably, no RCT has yet reported survival comparisons, although the phase III LANCE trial is currently evaluating MIS vs. open laparotomy in this setting (9,27,91). However, multiple large observational studies and meta-analyses in the last 5 years consistently reported no OS disadvantage with MIS and some even suggest non-inferiority or parity in survival (34,88,89).

A comprehensive 2023 analysis of nearly 7,900 patients from the U.S. National Cancer Database (https://www.facs.org/quality-programs/cancer-programs/national-cancer-database/) demonstrated no notable difference in overall survival between MIS and open surgery for interval debulking after NACT. After propensity score matching, the median OS was ~46.7 months with MIS vs. 41.0 months with laparotomy (HR, 0.86; 95% CI, 0.79–0.94); 5-year survival probabilities were essentially equivalent (38.3% MIS vs. 34.8% open; P<0.01 in favor of MIS. This apparent advantage may have been influenced by differences in patient selection). There was no detriment to survival with MIS, if anything, MIS reported a slight survival benefit in this weighted analysis (27). This aligns with a Japanese Gynecologic Oncology Committee meta-analysis (2024) which reported no notable OS differences between MIS and open approaches in advanced-stage disease, whether for PDS or IDS. For instance, in advanced primary debulking cases, the pooled odds of survival were similar (OR, ~0.66; 95% CI, 0.36–1.22; P>0.05), and likewise no OS disadvantage was seen for MIS IDS (OR, ~0.93; CI 0.25–3.44) (88).

PFS has also been reported to be equivalent between minimally invasive and open surgery approaches. Numerous studies found no notable PFS difference between MIS and open surgery groups (20). In a meta-analysis of 6 studies (3,528 patients) focusing on IDS after NACT, MIS was associated with a trend toward improved PFS but no OS difference (89). Specifically, patients in the MIS group had slightly improved PFS in some cohorts, possibly due to selection of improved responders, but on the whole PFS is equivalent when accounting for confounders. For example, Alletti et al (92) reported median PFS of 18 months with laparoscopy vs. 12 months with open in a single-center IDS series, but no difference in 5-year OS. In the pooled analysis of six studies (3,528 patients) after NACT, MIS was associated with a median PFS of 15.8–18.0 months vs. 12.0–14.2 months with open surgery, translating into an absolute PFS gain of 1.6–3.8 months. From meta-analysis data, the pooled hazard ratio for progression was 0.85 (95% CI, 0.73–0.99; P=0.04), indicating a 15% lower risk of progression with MIS, even though overall survival did not differ between the groups (89).

Several individual center studies and registry analyses further support OS parity. A study by Pereira et al (90) reported that 5-year survival rates were comparable with MIS. In their analysis, 47.5% of patients with MIS IDS were alive at 5 years vs. 30% of patients with open IDS (41 vs. 28% for MIS vs. open PDS). While such differences reflect selection factors, MIS did not compromise long-term survival in appropriate candidates. Additionally, a recent conference report including >2,400 interval debulking cases with R0 resection reported median OS ~51 months MIS vs. 46 months open, a difference that was not statistically significant (HR, ~1.1; P=0.17) (92). Taken together, current evidence indicated that overall survival with MIS in advanced ovarian cancer is comparable to open surgery, provided patients are selected for achievable complete cytoreduction (88,93).

Beyond survival duration, the pattern and timing of disease recurrence are important considerations. Thus far, studies have not identified any unique or worse recurrence patterns associated with minimally invasive debulking. Recurrence rates appear similar between MIS and open approaches in advanced-stage patients. For patients with advanced-stage (FIGO III–IV) EOC undergoing interval debulking after NACT, Zeng et al (89) performed a meta-analysis of six studies encompassing 3,528 patients and found no significant difference in recurrence rates between minimally invasive surgery and open laparotomy groups. In a dual-center retrospective cohort of 89 patients with stage IIIC-IV EOC (59 MIS vs. 30 open IDS), Pereira et al (90) reported equivalent recurrence frequencies in both approaches. Similarly, Alletti et al (92) evaluated 46 patients with stage III EOC (23 MIS vs. 23 open IDS) and observed no increase in early or atypical recurrences with minimally invasive techniques. A single-center comparison of robotic vs. open cytoreduction reported that the recurrence-free survival was longer in the MIS cohort (potentially reflecting case-specific factors such as patient selection bias, tumor stage distribution, preoperative disease burden, performance status or differences in adjuvant therapy protocols), but recurrence frequency was similar across groups. No study to date has demonstrated a higher risk of recurrence solely due to the minimally invasive technique when surgical completeness is equivalent (34).

A specific concern with MIS is the risk of port-site metastases (tumor seeding at trocar sites). Port-site metastases have been documented in advanced ovarian cancer after diagnostic laparoscopy, with rates of 5–17% reported when no precautions were taken. However, these metastases are usually detected at the time of subsequent surgery or during chemotherapy and are resected or sterilized by treatment. Furthermore, long-term follow-up has indicated no adverse impact on prognosis from port-site implants if patients receive standard therapy (94). In a novel published series of MIS IDS (from 2015 onwards), port-site recurrences were rare (>1–2% of cases) and have not been reported as a notable pattern of failure compared to the overall recurrence rates in ovarian cancer (89,95). The majority of recurrences after either MIS or open debulking occur in typical intra-abdominal locations (peritoneum and retroperitoneum account for 75–80% of recurrence sites), with remaining recurrences distributed among distant sites (liver, brain and lungs), reflecting the biology of ovarian cancer compared with the surgical route (42,94). Overall, current evidence suggests no difference in recurrence patterns between MIS and open surgery; the key determinant is whether complete cytoreduction is achieved, not the incision type (89). Notably, no increase in distant or early recurrence has been observed with MIS, unlike early-stage cervical cancer MIS trials (95). Ongoing studies will continue to monitor for any subtle differences in recurrence dynamics with MIS.

Patient selection is a key factor in the success of minimally invasive cytoreductive surgery. Several previous studies emphasize that MIS in advanced ovarian cancer should be reserved for patients with a limited disease burden that can be addressed with standard cytoreductive techniques not requiring extensive multiorgan resections. Common selection criteria include: Notable response to NACT (for interval cases) with substantial tumor shrinkage; disease distribution confined to areas amenable to laparoscopic resection (for example, superficial peritoneal implants, easily accessible pelvic/abdominal disease, omental caking that can be removed en bloc); absence of extensive diaphragmatic or mesenteric disease requiring large incisions; and patient factors such as body habitus and comorbidities that favor a minimally invasive approach (42,94). In practice, surgeons often perform a thorough preoperative imaging assessment and may even use diagnostic laparoscopy to confirm that complete resection may be feasible via MIS ports (89).

Previous studies demonstrated that when these selection principles are applied, patients with MIS tend to have lower initial tumor load. For example, in the National Cancer Database (NCDB; http://www.facs.org/quality-programs/cancer/ncdb/) study, MIS cases had significantly fewer ‘additional cytoreductive procedures’ (for example, bowel or spleen resections) compared with open cases (59.3 vs. 70.8%; P<0.01). This suggests surgeons selected MIS for patients with less disseminated disease, hence needing fewer organ resections. In the same dataset, the rate of any gross residual disease was slightly lower in patients with MIS (23.9 vs. 26.7% in open; corresponding to higher complete resection rates) (27), which suggested that surgeons attempted MIS primarily in cases where they anticipated achieving R0. Another analysis noted patients with MIS were less likely to require ‘extensive’ surgery compared with open patients (41 vs. 53%; P<0.001). All of this reflects a selection bias: Candidates for MIS are typically those with resectable disease of low complexity (42,93). A multi-center consensus concluded that MIS is appropriate when surgery can be limited to standard cytoreductive procedures without major complexity (42).

Beyond tumor factors, patient factors serve a role; a previous study reported that patients with MIS were on average older compared with those undergoing open surgery (93), possibly because surgeons chose MIS to minimize morbidity in older patients (≥65 years) who had adequate response to chemotherapy. Other selection considerations include performance status and surgeon experience. High-volume centers with advanced MIS skills are more likely to attempt laparoscopy/robotics on borderline cases, whereas less experienced centers might opt for laparotomy for the same patient. In summary, ideal candidates for MIS PDS/IDS are those with regionally confined disease, notable response to therapy and no need for large en bloc resections, as determined by imaging or laparoscopic assessment. These selection criteria underlie the similar outcomes seen, and differences in the characteristics of the patient groups, such as age, comorbidities, response to chemotherapy and extent of disease, rather than the surgical approach itself, may account for any modest benefits observed in the MIS cohorts (27,89).

Although outcomes thus far are encouraging, it is important to acknowledge the limitations of existing data. Selection bias is the foremost limitation, as all comparative studies to date are non-randomized and patients with MIS inevitably had more favorable disease characteristics. Propensity score matching and multivariable adjustments, as performed in the NCDB analyses (27), help mitigate but cannot eliminate this bias. Thus, it remains possible that equivalent patients with extensive disease would fare differently with MIS compared with open surgery. High-level evidence from randomized trials to confirm oncological safety.

To date, no RCT has published definitive results comparing MIS vs. open debulking in advanced ovarian cancer (34). However, the first such trial is presently underway. The international LANCE trial is a phase III multicenter RCT designed to evaluate non-inferiority of MIS vs. laparotomy for IDS in advanced-stage ovarian cancer after 3–4 cycles of NACT (95). The pilot phase of the trial demonstrated feasibility and acceptable conversion rates, enabling full accrual. The outcome of the trial (disease-free survival as primary endpoint) will provide level I evidence on the oncological efficacy of MIS in this setting (9,95). Therefore, until the LANCE trial results are reported, the present review relied on observational data.

Another limitation is that most studies have been conducted in specialized centers or databases from developed healthcare systems, which may not reflect all practice settings globally. There is a paucity of data on MIS outcomes in resource-limited regions or low-volume centers. Additionally, follow-up duration in previous MIS series was still short, as several studies reported a median follow-up of 3–4 years, so long-term survival equivalence and patterns of late recurrence require continued investigation (42). Data on recurrence patterns specifically (for example whether MIS might lead to different metastatic spread) are limited. To date, no concerning safety issues or unexpected complications have been reported. Numerous analyses (for example, NCDB) lack specific details such as exact residual tumor size or QoL outcomes. QoL and recovery metrics may favor MIS (due to faster recovery), but robust prospective data on patient-reported outcomes are needed.

In summary, although current evidence supports MIS as an acceptable approach in advanced ovarian cancer, it is still largely retrospective. Results must be interpreted with caution given the non-randomized nature of published studies and potential confounders (34). The ongoing LANCE RCT and other prospective studies will be key to conclusively establish whether MIS is comparable with open surgery in all oncological outcomes or if differences may emerge when selection bias is removed. To date, the National Comprehensive Cancer Network (NCCN) and the European Society of Gynecological Oncology (96) guidelines emphasize that MIS for advanced ovarian cancer should be offered only in highly selected patients by experienced surgeons, preferably in the context of clinical trials or protocols (38,89). Furthermore, current evidence is largely derived from retrospective studies with inherent selection biases. While several cohort analyses indicate non-inferior outcomes for MIT compared with open surgery, the lack of level I evidence from completed RCTs mandates cautious interpretation. The ongoing LANCE trial is expected to address this gap.

Real-world data from high-volume gynecological oncology centers have consistently reported that in appropriately selected patients, MIS can safely replicate the oncological outcomes of open cytoreduction. For instance, the NCDB analyses demonstrated that between 2013 and 2019, MIS usage in IDS increased significantly in the USA, with comparable overall survival (OS) and even lower perioperative mortality compared with open surgery (90-day mortality; 1.4 vs. 2.5%; P<0.01) (27). Similar findings were reported by the MISSION study in Europe and South America (42) and by multi-center registries from including a 2022 meta-analysis (89). These studies confirmed equivalent 5-year OS rates and high R0 rates with MIS when performed by experienced teams (90,92). MIS has also been associated with faster recovery, shorter hospital stays and earlier initiation of postoperative chemotherapy in some cohorts (93). Collectively, these real-world data suggest the feasibility and safety of MIS for advanced ovarian cancer and support its broader implementation when patient selection and surgical expertise are appropriate.

However, comprehensive data specifically addressing QoL in advanced-stage EOC are limited. While some retrospective analyses and small prospective series suggest potential QoL benefits, large, well-powered studies are needed to establish definitive conclusions. Furthermore, while some studies have utilized validated patient-reported outcome instruments such as the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ)-Core 30 and QLQ-Ovarian Cancer Module 28 to assess postoperative QoL in patients with EOC, robust PRO data specific to advanced-stage disease remain sparse and warrant further prospective investigation (97).

Currently, there is a lack of consensus in the field of gynecological oncology on the definition of ‘early stage’ ovarian cancer and its management. Typically, gynecological oncologists identify most EOC types at an advanced stage and the standard surgical intervention involves primary cytoreduction, followed by discrimination (12,13). However, two distinct cohorts of patients with apparently early-stage disease (those with Stage I disease on imaging who are ultimately found to have advanced disease at surgery and those with localized Stage I disease) may potentially gain from varying management approaches. In the early stages of the disease, surgery could lead to the diagnosis of Stage IIIB serous carcinoma, which may cause the disease stage to progress (12,13).

The NCCN guidelines currently advocate conducting the standard staging of surgical procedures for tumors classified as small stage I diseases (99). An alternative biological perspective suggested evaluating an early suspicious pelvic and/or para-aortic stage from a clinical standpoint. It is possible for these rare conditions to be caused by nodal endometriosis or dermoids or these conditions may be associated with a slow progression of hematogenous lymphangiomatosis, which usually occurs when endometriosis stays the same (38,57,92,100). Currently, research on the origins of these small, less aggressive atypical nodular forms of cancer is being conducted. The surgical techniques should vary when executed in a gynecology unit focused on these distinct procedures. Only certain patients qualify as suitable candidates for MIS in cases of advanced stage disease: i) Patients with documented major response to NACT, defined by imaging or laparoscopic assessment showing >80% reduction in tumor volume and confinement of residual disease to easily accessible pelvic and omental sites; ii) individuals whose disease distribution is limited to superficial peritoneal implants, minor omental caking that can be removed en bloc and absence of extensive diaphragmatic or mesenteric involvement; iii) cases without bulky upper abdominal disease or large bowel, splenic or hepatic surface metastases, such that no multiorgan resections are anticipated; iv) patients with Charlson comorbidity index <2 and adequate performance status (ECOG 0–1), minimizing anesthesia risk and facilitating rapid postoperative recovery; v) selected older patients (aged ≥65 years) with limited tumor burden who stand to benefit most from reduced perioperative morbidity and shorter hospital stays; and vi) selected older patients (aged ≥65 years) with limited tumor burden who stand to benefit most from reduced perioperative morbidity and shorter hospital stays.

The feasibility and safety of MIS in selected patients has been demonstrated in the MISSION study, where 96% achieved no gross residual disease via MIS after NACT and conversion to laparotomy occurred in only 3.9% of cases (57,92). It could be suggested that patients should have: i) Imaging after clinical evaluation by the multidisciplinary team with radiological diagnosis; ii) FIGO stage IIIC or less; iii) Charlson comorbidity index <2 (100); iv) pauci-symptomatic small disease; v) imaging with pre-operative diagnostic laparoscopy; and vi) no notable protein anemia. As for the patients with carcinoma in situ (CIS), strong de-swelling surgical procedures should be avoided; albumin and hemoglobin must be normal; albumin and creatinine must be normal; fitness status and adequate psycho-physiological support; no overfeeding of the pathology or performance status; and ovarian clear cell carcinoma and CIS, against serous papillary histotype required.

Proper patient selection is key to achieve favorable outcomes in MIS. While early-stage disease, lower histological aggressiveness and a lower Charlson comorbidity index favor the feasibility of this approach, further research is required to validate these selection criteria across diverse patient populations and advanced-stage cases.

The role of MIS in the management of ovarian cancer has been well documented in the form of low invasive techniques such as laparoscopic, robotic or single port surgery. Consequently, the approach has been associated with favorable reports in terms of blood loss, time, length of stay, wound complications and recovery time. However, despite favorable outcomes for recurrence, mortality and overall survival for patients receiving MIS, favorable surgical results are only associated with centers that have extensive experience in MIS.

The viability of hepatobiliary cytoreduction is markedly influenced by the skill level of the surgeon and the available resources at the institution. Previous studies have demonstrated that high-volume centers tend to achieve superior oncological outcomes compared with lower-volume centers (42,89,98). Di Donato et al (98) demonstrated that complete cytoreduction can be achieved in patients with hepatobiliary metastases when conducted in specialized centers with a multidisciplinary approach. In this situation, procedures such as sentinel node mapping and the removal of lymph nodes using minimally invasive methods have been recognized as important (42,89,98). However, these procedures should only be performed by surgeons with documented expertise in minimally invasive debulking surgery, following established institutional guidelines and quality standards to ensure patient safety and adequate disease management.