Mininvasive Cytoreduction Surgery plus HIPEC for Epithelial Ovarian Cancer: A Systematic Review.

Background and objectives: The Gold-Standard treatment for Advanced Epithelial Ovarian Cancer remains cytoreductive surgery followed by systemic chemotherapy. Surgery can be performed either by an open or minimally invasive approach (MIS), although the former remains the most widely used approach. Recently, Van Driel et al. proved that adding 100 mg/m2 of Cisplatin in Hyperthermic Intraperitoneal Chemotherapy (HIPEC) at Interval Debulking Surgery (IDS) gives a disease-free survival (DFS) advantage. Similarly, Gueli-Alletti et al. demonstrated how the MIS approach is feasible and safe in IDS. Moreover, Petrillo et al. reported pharmacokinetic profiles with a higher chemotherapy concentration in patients undergoing HIPEC after MIS compared with the open approach. Therefore, the following review investigates the oncological and clinical safety consequences of the association between MIS and HIPEC. Methods: Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically searched the PubMed and Scopus databases in April 2022. Studies containing data about oncological and safety outcomes were included. We registered the Review to the PROSPERO site for meta-analysis with protocol number CRD42022329503. Results: Five studies fulfilled inclusion criteria. 42 patients were included in the review from three different Gynecological Oncological referral centers. The systematic review highlighted a Recurrence Rate ranging between 0 and 100%, with a 3-year Platinum-Free Survival between 10 and 70%. The most common HIPEC drug was Cisplatin, used at concentrations between 75 and 100 mg/m2 and at an average temperature of 42 °C, for 60 to 90 min. Only 1 Acute Kidney Insufficiency has been reported. Conclusions: The scarcity of clinical trials focusing on a direct comparison between MIS and the open approach followed by HIPEC in EOC treatment does not make it possible to identify an oncological advantage between these two techniques. However, the safety profiles shown are highly reassuring.

Pharmacokinetics of cisplatin during open and minimally-invasive secondary cytoreductive surgery plus HIPEC in women with platinum-sensitive recurrent ovarian cancer: a prospective study.

OBJECTIVE: Evidences from animal models seem to suggest that minimally invasive surgery may enhance cisplatin diffusion when the drug is administered in the context of post-operative hyperthermic intraperitoneal chemotherapy (HIPEC). The present study evaluates the cisplatin pharmacokinetic profile in a prospective series of women with platinum sensitive recurrent epithelial ovarian cancer treated with open secondary cytoreductive surgery (O-SCS) or minimally-invasive secondary cytoreductive surgery (MI-SCS). METHODS: Cisplatin levels were assessed at 0, 20, 40, 60, and 120 minutes in: 1) blood samples, 2) peritoneal perfusate, and 3) peritoneal biopsies at the end of HIPEC. Median Cmax has been used to identify women with high and low drug levels. Progression-free survival (PFS) was calculated as the time elapsed between SCS+HIPEC and secondary recurrence or last follow-up visit. RESULTS: Nine (45.0%) women received MI-SCS, and 11 (55.0%) O-SCS. At 60 minutes, median cisplatin Cmax in peritoneal tissue was higher in patients treated with MI-SCS compared to O-SCS (Cmax=8.262 µg/mL vs. Cmax=4.057 µg/mL). Furthermore, median cisplatin plasma Cmax was higher in patients treated with MI-SCS compared to O-SCS (Cmax=0.511 vs. Cmax=0.254 µg/mL; p-value=0.012) at 120 minutes. With a median follow-up time of 24 months, women with higher cisplatin peritoneal Cmax showed a longer PFS compared to women with low cisplatin peritoneal levels (2-years PFS=70% vs. 35%; p-value=0.054). CONCLUSIONS: We demonstrate for the first time that minimally invasive route enhances cisplatin peritoneal tissue uptake during HIPEC, further evaluations are needed to confirm the correlation between peritoneal cisplatin levels after HIPEC and survival. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01539785.

Cytoreductive surgery followed by HIPEC repetition for secondary ovarian cancer recurrence.

Secondary and tertiary cytoreductive surgery was associated with improved overall survival in platinum-sensitive recurrent ovarian cancer (ROC). Hyperthermic intraoperative intra-peritoneal chemotherapy (HIPEC) is considered an attractive method in the treatment of ROC to deliver chemotherapy with enhanced effect directly at the tumor site. However, another deserving aspect is the feasibility and the oncologic role of HIPEC repetition. Twelve patients affected by secondary ovarian cancer recurrence previously submitted to cytoreduction followed by HIPEC were enrolled for the present study to receive tertiary cytoreduction followed by HIPEC repetition. The median operative time, including time for HIPEC procedure, was 360 min (range 240-540). Average EBL was 325 ml (from 100 to 500 ml). The median hospital stay was of 5 days, from 4 to 10. Low-grade post operatory complications occurred in 2 patients (16.6%) and high-grade complication in 1 case (8.3%). Our study report encouraging data about safety of HIPEC repetition in ovarian cancer treatment.

Minimally invasive secondary cytoreduction plus HIPEC versus open surgery plus HIPEC in isolated relapse from ovarian cancer: a retrospective cohort study on perioperative outcomes.

STUDY OBJECTIVE: To compare the perioperative outcomes of minimally invasive secondary cytoreduction surgery (SCS) plus hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) versus open surgery plus HIPEC in a group of platinum-sensitive patients with advanced epithelial ovarian cancer (AEOC) with isolated relapse. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome, Italy. PATIENTS: We selected 22 patients with a peritoneal cancer index value of 2. The laparoscopic group consisted of 11 patients who underwent laparoscopic and/or robotic complete cytoreduction plus HIPEC, whereas the laparotomic group consisted of 11 patients who underwent complete laparotomic cytoreduction plus HIPEC. INTERVENTIONS: The minimally invasive surgery (MIS) group were platinum-sensitive single recurrent ovarian cancer patients who underwent either laparoscopic or robotic complete secondary cytoreduction plus HIPEC, whereas the open group were women with similar clinical characteristics who underwent complete secondary cytoreduction plus HIPEC by laparotomy. MEASUREMENTS AND MAIN RESULTS: The median operative time, calculated from the skin incision to the end of SCS (i.e., excluding HIPEC phase) was 125 min (range 95-150 min) in the MIS group and 295 min (range 180-420) in the open group (p = .001), with a median estimated blood loss of 50 mL (range 50-100) and 500 mL (range 50-1300), respectively (p = .025). The median length of hospital stay was 4 days (range 3-17) in the MIS group and 8.5 days (range 4-30) in the open group (p = .002). No statistically significant differences were registered in terms of intra- and postoperative complications between the 2 groups. CONCLUSION: The minimally invasive approach for SCS plus HIPEC is safe and efficient in terms of toxicity and postoperative outcomes for single isolated relapse. HIPEC should not be considered a major contraindication to a minimally invasive approach.