Gynecologic Oncology 200 (2025) 161–168

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Gynecologic Oncology

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The role of hyperthermic intraperitoneal chemotherapy (HIPEC) in

ovarian cancer
Giorgio Bogani a,⁎, Anna Fagotti b, Vito Chiantera c, Pierandrea De Iaco d,k, Enrico Vizza e, Paolo Scollo f,
Marco Petrillo g, Andrea Giannini h, Violante Di Donato h, Francesco Raspagliesi a, Giuseppe Vizzielli i,j
a
Gynecologic Oncologic Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
b
Department Woman and Child Health and Public Health, Fondazione Policlinico Universitario A, Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
c
Department of Gynecologic Oncology, Istituto Nazionale Tumori - Fondazione “G. Pascale” IRCCS, Naples, Italy
d
IRCCS Azienda Ospedaliero-Universitaria di Bologna, Division of Oncologic Gynecology, Bologna, Italy
e
Gynecologic Oncology Unit, Department of Experimental Clinical Oncology, IRCSS-Regina Elena National Cancer Institute, Rome, Italy
f
Department of Obstetrics and Gynecology, Cannizzaro Hospital, University of Enna “Kore” (D'Agate and Scibilia), 95126 Catania, Italy
g
Department of Obstetrics and Gynecology, University of Sassari, Sassari, Italy
h
Department of Gynecological, Obstetrical and Urological Sciences, “Sapienza” University of Rome, 00185 Rome, Italy
i
Clinic of Obstetrics and Gynecology, “Santa Maria della Misericordia” University Hospital, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy
j
Department of Medicine (DMED), University of Udine, Udine, Italy
k
University of Bologna, Department of Medical and Surgical Sciences (DIMEC), Bologna, Italy

H I G H L I G H T S

• HIPEC might improve survival when combined with cytoreductive surgery in advanced ovarian cancer.
• Evidence supports the efficacy of HIPEC in interval debulking and selected cases of recurrent ovarian cancer.
• Optimal patient selection and complete cytoreduction are crucial to maximizing the benefits of HIPEC.

a r t i c l e i n f o a b s t r a c t

Article history: Objectives. Hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly recognized as an effective
Received 4 June 2025 addition to cytoreductive surgery in advanced ovarian cancer, particularly in patients who respond to
Received in revised form 21 July 2025 platinum-based chemotherapy.
Accepted 25 July 2025
Methods. A systematic review of phase III randomized controlled trials testing the role of HIPEC in ovarian
Available online xxxx
cancer was performed, according to the PRISMA guidelines.
Keywords:
Results. Seven randomized controlled trials were included. Data of 1252 patients with ovarian cancer were
HIPEC examined: 630 and 622 having surgery plus HIPEC and surgery alone, respectively. This review critically
Ovarian cancer evaluates the role of HIPEC in various clinical scenarios, including primary and interval debulking surgery and
Interval debulking surgery secondary cytoreduction. Evidence from key clinical trials is summarized, focusing on its effects on
Secondary cytoreductive surgery progression-free and overall survival. Important factors such as patient selection, chemotherapy regimens, tech-
nical procedures, and perioperative care are examined. Potential side effects (including renal toxicity, gastroin-
testinal injury, and delayed recovery) are discussed. The review also assesses cost-effectiveness and
integration of HIPEC into multidisciplinary treatment plans. Emerging approaches, such as combining HIPEC
with targeted therapies and personalized treatment strategies, are explored.
Conclusions. While HIPEC offers a promising therapeutic advance, further high-quality studies are needed to
refine its use and assess its role in earlier stages of disease. This review aims to inform clinical decisions and
support future research in the evolving management of ovarian cancer.
© 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar tech-
nologies.

⁎ Corresponding author.
E-mail address: [Link]@[Link] (G. Bogani).

[Link]
0090-8258/© 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
G. Bogani, A. Fagotti, V. Chiantera et al. Gynecologic Oncology 200 (2025) 161–168

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
1.1. HIPEC in ovarian cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
1.2. Primary debulking surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
1.3. Interval Debulking Surgery (IDS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163
1.4. HIPEC in recurrent ovarian cancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
2. Future directions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166
2.1. Exploring combination therapies with HIPEC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166
2.2. Improved patient selection and surgical techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166
2.3. Managing toxicity and postoperative care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166
2.4. Expanding access and cost-effectiveness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166
3. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
CRediT authorship contribution statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167

1. Introduction 1.1. HIPEC in ovarian cancer

Ovarian cancer is the most lethal gynecologic malignancy and HIPEC has gained growing attention in the treatment of ovarian
accounts for the highest mortality among gynecological cancers in cancer. The aim of this systematic review is to collect data from random-
developed countries [1]. Despite advances in diagnostic methods and ized trials testing the value of HIPEC in subjects with advanced/
treatment strategies, the overall 5-year survival rate remains low (ap- recurrent ovarian cancer. The review followed the suggestions from
proximately 30–40 %), mainly due to late-stage diagnosis [1]. The dis- the Preferred Reporting Items for Systematic Reviews and Meta-
ease often presents with vague and nonspecific symptoms, leading to Analyses (PRISMA) statement [13]. Data were extracted from random-
delayed detection and extensive peritoneal spread at diagnosis [1]. ized controlled trials (RCT). The search was comprehensive, using
Surgery is a key component in the management of ovarian cancer, several databases from each database's earliest inception to 30 June
both at initial presentation and, in selected cases, at recurrence [2–4]. 2025. PubMed (MEDLINE), Embase, CENTRAL, Scopus, and Web of Sci-
For newly diagnosed patients, standard treatment includes cyto- ence databases, as well as [Link] were systematically
reductive surgery (CRS) combined with platinum-based chemotherapy searched and supplemented by secondary screening of the references
(with or without maintenance therapy) [1,2]. The prognostic value of of all studies included. We searched for abstracts and conference pro-
complete cytoreduction (defined as no visible residual disease (CC-0 ceedings as well. Two (GB, GV) authors independently screened records
resection)) is well established [1]. In a pooled analysis of three random- retrieved through the search strategy from titles and abstracts. Poten-
ized trials, Du Bois et al. showed that complete tumor resection is the tially relevant studies were acquired in full text and assessed for final in-
strongest predictor of overall survival, with median overall survival ex- clusion independently by two authors. Any disagreement was discussed
ceeding 60 months in patients undergoing CC-0 resection [2]. In the re- with the other authors.
current setting, the role of surgery is more controversial. The DESKTOP The database search identified 1065 records. Based on study eligibil-
trials by the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) ity criteria, seven studies were included for the quantitative synthesis.
have provided evidence to guide patient selection for secondary Fig. 1 shows the PRISMA flow chart. Notably, HIPEC has been studied
cytoreductive surgery. The DESKTOP I study introduced the AGO score in combination with primary debulking surgery, interval debulking fol-
(a predictive model based on performance status, absence of ascites, lowing neoadjuvant chemotherapy, and secondary cytoreductive sur-
and complete resection during primary surgery) to identify patients gery, administered either before or after systemic therapy. We found
most likely to benefit from secondary cytoreductive surgery [3]. studies reporting data on HIPEC at the time of primary debulking sur-
DESKTOP III later confirmed a survival benefit when complete resection gery (n = 2) [7,11], interval debulking surgery (n = 4) [5,7,11,12],
was achieved, with a median overall survival of 53.7 months in the and secondary cytoreductive surgery (n = 4) [8–11]. Data of 1252 pa-
surgical group versus 46 months in the non-surgical group [4]. tients with ovarian cancer were examined: 630 and 622 having surgery
Hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged plus HIPEC and surgery alone, respectively. Table 1 summarizes
as a promising adjunct to CRS, especially in patients with newly diag- evidence in across various clinical settings [5–12].
nosed or recurrent ovarian cancer [5–12]. HIPEC involves the intraoper-
ative delivery of heated chemotherapy directly into the peritoneal 1.2. Primary debulking surgery
cavity after surgical debulking. The elevated temperature enhances
drug penetration and cytotoxicity while exerting direct thermal damage In treatment-naïve patients with advanced ovarian cancer, emerging
to tumor cells. By targeting microscopic residual disease, HIPEC aims to retrospective evidence suggests that HIPEC following CRS may confer a
lower recurrence risk and improve long-term outcomes, with poten- significant survival benefit [14–16]. In a retrospective multicenter study
tially reduced systemic toxicity [5–12]. conducted in China, Lei et al. evaluated 584 patients with FIGO stage III
While the role of HIPEC in newly diagnosed ovarian cancer is still disease and reported a median overall survival of 49.8 months in pa-
under investigation, its use in recurrent disease remains debated due tients undergoing primary debulking surgery with HIPEC, compared to
to mixed results from clinical studies. This review evaluates current 34.0 months in those treated with surgery alone [14]. Similarly,
evidence on HIPEC in primary and interval debulking surgeries as well Karanikas et al., in a retrospective analysis, reported 5- and 10-year
as in recurrence. We critically analyze its therapeutic potential, limita- overall survival rates of 69.6 % and 64.2 %, respectively, in patients
tions, and the challenges in incorporating HIPEC into standard clinical treated with CRS plus HIPEC (n = 79), compared to 40.8 % and 35.0 %
practice. in the CRS-alone group (n = 72). The adjusted hazard ratio (aHR) for

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G. Bogani, A. Fagotti, V. Chiantera et al. Gynecologic Oncology 200 (2025) 161–168

Fig. 1. PRISMA flow chart.

all-cause mortality in the HIPEC group was 0.33 (95 % CI: 0.17–0.63, p = the relatively small sample size (245 patients), a modest absolute
0.001). Additionally, both disease-specific survival and disease-free difference in events (n = 15), and a limited number of deaths (n =
survival were significantly improved, with aHRs of 0.25 (p = 0.003) 8)) warrant cautious interpretation [5,6].
and 0.54 (p = 0.041), respectively [15]. Conversely, subgroup analysis The findings were further supported by the KOV-HIPEC-01 trial
from the Korean randomized trial (NCT01091636) failed to demon- (NCT01091636), in which Lim et al. reported a median progression-
strate a survival benefit from HIPEC in the primary debulking surgery free survival of 17.4 months in the HIPEC group versus 15.4 months in
setting [7]. These results underscore the need for further prospective, the control group, and median overall survival of 61.8 versus
adequately powered studies to definitively assess the therapeutic 48.2 months, respectively (n = 92 per arm) [7]. However, it is important
value of HIPEC at the time of primary debulking surgery. To date, to highlight that the study was not powered to assess the role of HIPEC
HIPEC at the time of primary debulking surgery, should be offered in patients undergoing IDS. Moreover, enrollment into the trial was not
only in the context of clinical trials. stratified by type of surgery, stage, BRCA status, or homologous recom-
bination deficiency, potentially introducing biases in the interpretation
1.3. Interval Debulking Surgery (IDS) of the results.
The study also demonstrated the cost-effectiveness of HIPEC, with
The role of hyperthermic HIPEC in interval debulking surgery has an incremental cost-effectiveness ratio (ICER) within acceptable thresh-
been validated by several phase III trials. In 2018, van Driel et al. demon- olds for advanced oncologic therapies, highlighting both the clinical and
strated the efficacy of HIPEC in a randomized trial comparing IDS plus economic value of the approach [17]. In a Phase II trial, Batista et al. in-
HIPEC versus IDS alone in patients with advanced ovarian cancer [5]. vestigated a short-course HIPEC regimen during IDS. Despite the limited
The study reported a median PFS of 14.2 months in the HIPEC group sample size (n = 15), the study suggested that abbreviated HIPEC pro-
compared to 10.7 months in the control group (HR: 0.66; 95 % CI: tocols may be feasible and potentially effective for selected patients
0.50–0.87; p = 0.03), and a median overall survival of 45.7 versus [18].
33.9 months, respectively (HR: 0.67; 95 % CI: 0.48–0.95; p = 0.02). Accumulating evidence supports the use of HIPEC during IDS follow-
Updated results from the OVHIPEC-1 trial confirmed the long-term sur- ing neoadjuvant chemotherapy. The intraperitoneal administration of
vival benefit of HIPEC in patients with FIGO stage III epithelial ovarian heated chemotherapy allows for high locoregional drug concentrations,
cancer undergoing IDS [6]. However, limitations of the study (including enhancing cytotoxic effects while minimizing systemic exposure.

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Table 1
Main prospective phase III trials of HIPEC in ovarian cancer.

Study Setting Chemotherapeutic Agents Duration Number of Number of Median disease- Median overall Key Findings
of HIPEC Patients Treated Patients free survival survival (HR
(HIPEC arm) Treated (HR (95 %CI)) (95 %CI))
(Control arm)

Lim et al., 2022 [7] Primary debulking Cisplatin 75 mg/m2 90 min 58 49 19.8 vs. 18.8 mo 69.5 vs. 61.3 mo KOV-HIPEC-01 demonstrated that
surgery HIPEC did not improved outcomes in
1.16 (0.74, 1.83) 1.38 (0.75, 2.54) the ITT population.
Lim et al., 2022 [7] Interval debulking Cisplatin 75 mg/m2 34 43 17.4 vs. 15.4 mo 61.8 vs. 48.2 mo The addition of HIPEC to IDS provided
surgery an improvement of progression-free
0.60 (0.37, 0.99) 0.53 (0.29, 0.96) and overall survival (subgroup
analysis).
2
Villarejo Campos et al., 2024 Primary debulking Paclitaxel 175 mg/m 60 min 12 14 23 vs. 19 mo 48 vs. 46 mo Paclitaxel-based HIPEC showed
[11] surgery improved local disease control;
Villarejo Campos et al., 2024 Interval debulking Paclitaxel 175 mg/m2 19 7 NR NR survival outcomes not statistically
[11] surgery significant
Villarejo Campos et al., 2024 Recurrent ovarian Paclitaxel 175 mg/m2 1 2
[11] cancer
2
van Driel et al., 2018 [5] Interval debulking Cisplatin 100 mg/m 90 min 122 118 14.2 vs. 10.7 mo 45.7 vs. 33.9 mo OVHIPEC-1 showed improved OS (45.7
surgery vs. 33.9 months) and PFS (14.2 vs.
0.66 (0.50, 0.87) 0.67 (0.48, 0.94) 10.7 months) in HIPEC group during
IDS.
Cascales Campos et al. [12] Interval debulking Cisplatin 75 mg/m2 60 min 35 36 18 vs. 12 mo 52 vs. 45 mo After NACT, HIPEC improved
surgery disease-free and overall survival.
0.12 (0.02, 0.89) NR
Spiliotis et al., 2015 [10] Recurrent ovarian For platinum sensitive disease (n = 34): 60 min 60 60 NR 26.7 vs. 13.4 mo Significant OS benefit in
cancer cisplatin 100 mg/m2 and paclitaxel 175 mg/m2. platinum-sensitive disease treated
164

For platinum resistant disease (n = 26): NR NR with HIPEC.

doxorubicin 35 mg/m2 and paclitaxel 175 mg/m2
or mitomycin 10 mg/m2
Classe et al., 2024 [9] Recurrent ovarian Cisplatin 75 mg/m2 60 min 207 208 10.2 vs. 9.5 mo 54.3 vs. 45.8 mo CHIPOR trial showed significant OS
cancer improvement with HIPEC compared to
0·79 (0·63–0·99) 0·73 (0·56–0·96) controls.
Fagotti et al., 2024 [8] Platinum-sensitive Cisplatin 75 mg/m2 60 min 82 85 25 vs. 23 mo NR HORSE trial showed survival benefit in
recurrent OC sensitive disease with HIPEC.
NR NR

Abbreviation: HIPEC, Hyperthermic intraperitoneal chemotherapy; RCT, randomized controlled trial; OS, overall survival; PFS, progression-free survival; HR: Hazard ratio; CI, confidence interval; NR, not reported; mo, months.

Gynecologic Oncology 200 (2025) 161–168

G. Bogani, A. Fagotti, V. Chiantera et al. Gynecologic Oncology 200 (2025) 161–168

Table 2
HIPEC during Interval Debulking Surgery (IDS) for ovarian cancer.

Step Details

Patient Selection - Stage III/IV ovarian cancer that cannot be optimally debulked at initial surgery (due to extensive disease or poor performance status).
- Patients are treated with neoadjuvant chemotherapy (NACT) before undergoing IDS and HIPEC.
- Assess the patient's response to NACT, aiming for a decrease in tumor burden and better feasibility of optimal debulking surgery.
Preoperative Preparation - Preoperative imaging (US/CT/MRI/PET) to assess residual disease after NACT and determine potential for optimal debulking.
- Regular preoperative evaluations: blood tests, assessment of liver, kidney, and bone marrow function, and nutritional status.
- Thorough informed consent process, discussing the benefits and risks of combining IDS with HIPEC.
Interval Debulking Surgery - Surgery performed after 3–4 cycles of NACT, focusing on maximal debulking with the goal of leaving no more than 1 cm of residual disease.
(IDS)
- Depending on disease distribution, procedures may include peritonectomy, omentectomy, bowel resections, or diaphragm stripping.
- Surgeons aim to achieve optimal debulking to maximize the benefit of HIPEC by reducing tumor burden before chemotherapy is introduced.
Placement of HIPEC Catheters - Two catheters are typically placed in the peritoneal cavity (one for inflow and one for outflow).
- Catheters are carefully positioned to ensure even distribution of the heated chemotherapy solution.
- Catheters are connected to the HIPEC machine, which controls the temperature and flow of the chemotherapy solution.
Chemotherapy Agent Selection - Common chemotherapy agents include Cisplatin and Paclitaxel for ovarian cancer.
- Dosing typically:
- Cisplatin: 75–100 mg/m2.
- Paclitaxel: 60–100 mg/m2.
- Institutions may use alternative agents based on patient characteristics, tumor biology, or institutional protocols.
Heating of Chemotherapy - Chemotherapy solution is heated to 41–43 °C (105.8–109.4 °F) to enhance the cytotoxicity of the drugs.
- The chemotherapy is circulated throughout the peritoneal cavity for 60–90 min to maximize contact with cancer cells.
Perfusion and Circulation - Chemotherapy solution is continuously circulated to ensure even distribution within the peritoneal cavity.
- The HIPEC system ensures the solution remains at the prescribed temperature and allows for controlled perfusion rates.
Postoperative Care - Postoperative monitoring is critical, as patients may experience complications such as renal toxicity, gastrointestinal perforation, or infection.
- Close monitoring for signs of acute kidney injury, cardiovascular instability, or gastrointestinal complications is required.
- Pain management, fluid balance, and nutritional support are essential in the recovery phase.
Follow-Up and Monitoring - Postoperative imaging (e.g., CT scans) to evaluate the extent of remaining disease or recurrence.
- Regular blood tests to monitor chemotherapy-related toxicity, including renal and hepatic function, and blood cell counts.
- Follow-up visits to evaluate recovery, assess the effects of HIPEC, and monitor for recurrence.
Complications and - Renal toxicity is a significant concern due to the use of platinum agents (e.g., cisplatin). Ensure hydration and monitor renal function closely.
Management
- Risk of gastrointestinal perforation, bowel obstruction, or peritoneal adhesions as a result of the surgery and HIPEC procedure.
- Infection risk due to catheter placement and surgical wounds; appropriate antibiotic prophylaxis is essential.
Adjuvant Chemotherapy - Following IDS and HIPEC, patients typically receive systemic chemotherapy (platinum and taxane-based) to target any residual microscopic
disease.
- The timing and type of systemic chemotherapy depend on the patient's response to NACT and HIPEC, as well as their clinical condition.
Long-Term Follow-Up - Regular surveillance imaging (CT/MRI) and blood tests to monitor for recurrence.
- Monitoring for late effects of chemotherapy and surgery, including peripheral neuropathy, lymphedema, and cardiovascular issues.

Abbreviation: HIPEC, Hyperthermic intraperitoneal chemotherapy; IDS, interval debulking surgery; NACT, neoadjuvant chemotherapy; CT, computed tomography; US, ultrasound, MRI,
magnetic resonance imaging, PET, positron emission tomography.

Nevertheless, optimal patient selection remains paramount; favorable 60) to secondary cytoreductive surgery plus HIPEC (n = 60), reporting
factors include ECOG performance status 0–1 and the ability to achieve a significant improvement in overall survival for the HIPEC group, with
CC-0 or CC-1 cytoreduction [5–7]. Table 2 shows an example of HIPEC median overall survival of 26.7 months versus 13.4 months in the sec-
application during IDS. Ongoing research is focused on refining ondary cytoreductive surgery-only group (p = 0.006) [10]. The study
treatment parameters, evaluating predictive biomarkers such as BRCA emphasized the potential benefit of HIPEC, particularly in patients
mutation status and homologous recombination deficiency (HRD), with limited disease burden and platinum-sensitive recurrence [10].
and assessing long-term quality-of-life outcomes. A secondary analysis Conversely, the HORSE trial (NCT01539785), led by Fagotti et al., did
of the OVHIPEC trial suggested that patients with HRD/BRCA wild- not demonstrate a significant overall survival benefit with HIPEC [8].
type tumors derived greater benefit from HIPEC compared to those This multicenter randomized phase III trial enrolled patients with
with BRCA-mutated or non-HRD tumors [19]. However, this evidence platinum-sensitive recurrent ovarian cancer and evaluated the addition
remains preliminary. Further prospective studies are needed to define of cisplatin-based HIPEC to secondary cytoreductive surgery, finding no
the molecular and clinical profiles most likely to benefit from HIPEC statistically significant difference in overall survival between groups [8].
and to guide its integration into personalized treatment strategies. Key factors potentially explaining these results include patient selection
and suboptimal cytoreduction in some cases, which may have compro-
1.4. HIPEC in recurrent ovarian cancer mised HIPEC efficacy, as the procedure's success heavily depends on
achieving minimal residual disease. In contrast, the CHIPOR trial
Recurrent ovarian cancer remains a significant clinical challenge due (NCT01376752) yielded promising results. This phase III randomized
to its high relapse rates following initial treatment. HIPEC has been in- study in platinum-sensitive recurrent ovarian cancer showed a signifi-
vestigated as an adjunct to secondary cytoreductive surgery in this set- cant overall survival improvement in patients treated with chemother-
ting, providing localized chemotherapy delivery potentiated by apy plus secondary cytoreductive surgery and HIPEC compared to
hyperthermia [8–10]. While some studies have suggested survival ben- chemotherapy plus secondary cytoreductive surgery alone. The
efits of HIPEC in recurrent ovarian cancer, its role remains controversial CHIPOR trial included patients having 6 cycles of chemotherapy (with
due to conflicting results from clinical trials. or without bevacizumab) plus cytoreductive surgery. Patients with
Several investigations have focused on the survival advantage of macroscopically complete tumor resection (CC0 or CC1) were then ran-
HIPEC in platinum-sensitive recurrent disease, a subgroup more likely domly assigned to receive HIPEC (1-h infusion of cisplatin 75 mg/m2 in
to benefit from surgery. Spiliotis et al. conducted a randomized con- 2 L/m2 of serum at 41 ± 1 °C) or no HIPEC. After surgery, patients re-
trolled trial comparing secondary cytoreductive surgery alone (n = ceived standard-of-care maintenance therapy at the investigator's

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discretion. The study enrolled 415 patients (207 HIPEC, 208 no HIPEC). amplify the immunostimulatory effects of these agents, potentially im-
Specifically, the 5-year overall survival rate was 50 % in the HIPEC group proving clinical responses [29,30]. Similarly, integrating HIPEC with
versus 36 % in the control group (p = 0.03), underscoring the impor- targeted therapies like PARP inhibitors offers a dual mechanism of ac-
tance of optimal cytoreduction and stringent patient selection [9]. Un- tion, particularly effective in BRCA-mutated ovarian cancers [14]. More-
like the HORSE trial, CHIPOR included patients who received and over, the combination of HIPEC with gene therapies (such as tumor
responded to chemotherapy before surgery, similar to the interval suppressor gene delivery or oncogene silencing) holds promise in over-
debulking surgery setting, which likely contributed to the differing out- coming resistance pathways, thereby enhancing HIPEC's therapeutic ef-
comes [8,9,20]. ficacy [27]. Ongoing clinical trials, including those evaluating HIPEC
Beyond these pivotal trials, other studies have highlighted consider- combined with immunotherapy (e.g., GOG-3068, HOTT), are expected
able heterogeneity in HIPEC protocols, including variations in drug se- to clarify the most effective combinatorial strategies for ovarian cancer
lection, perfusion temperature, and duration [21–24]. Ansaloni et al. management [31].
reviewed these discrepancies, noting cisplatin as the preferred agent
for its intraperitoneal penetration and cytotoxicity, although carbo- 2.2. Improved patient selection and surgical techniques
platin and paclitaxel have also been used with varying success. The op-
timal temperature remains debated, with most protocols targeting Optimizing patient selection is critical to maximizing the efficacy of
41–42 °C to maximize efficacy while minimizing toxicity [23]. Zivanovic HIPEC, as its success largely depends on the extent of cytoreductive sur-
et al. further demonstrated that achieving CC-0 cytoreduction prior to gery and tumor biological factors, including BRCA mutation status. The
HIPEC is crucial, as residual macroscopic disease significantly reduces identification of predictive biomarkers for HIPEC response could facili-
HIPEC's survival benefit due to limited chemotherapy penetration tate personalized therapeutic approaches. Emerging technologies such
[24]. These findings reinforce the necessity of surgical expertise and me- as liquid biopsy and comprehensive genetic profiling hold promise in
ticulous patient selection to optimize outcomes. The conflicting results stratifying patients who are most likely to benefit from cytoreduction
from trials such as HORSE and CHIPOR highlight several challenges in combined with HIPEC [27]. Advances in imaging modalities, notably in-
applying HIPEC for recurrent ovarian cancer [8,9]. First, no data support traoperative fluorescence imaging, can enhance the precision of
the role of HIPEC in patients receiving surgery and HIPEC followed by cytoreductive surgery by enabling the detection of microscopic tumor
chemotherapy [8,24]. The influence of preoperative chemotherapy on deposits that might otherwise remain undetected [32]. Additionally,
tumor biology and its role in identifying patients who may benefit the adoption of robotic-assisted surgical techniques is expanding, offer-
from HIPEC warrants further investigation. Second, the variability in ing improved surgical accuracy and reduced perioperative morbidity,
HIPEC protocols complicates cross-study comparisons and interpreta- which may contribute to more complete cytoreduction and, conse-
tion. Finally, achieving optimal cytoreduction remains a fundamental quently, improved HIPEC outcomes [33,34].
prerequisite for successful HIPEC, underscoring the need for experi-
enced surgical teams and strict patient selection criteria. 2.3. Managing toxicity and postoperative care

2. Future directions Despite its localized administration, HIPEC carries significant risks,
including nephrotoxicity, neurotoxicity, and gastrointestinal toxicity,
A major limitation in the widespread implementation of HIPEC for primarily attributable to platinum-based agents such as cisplatin [35].
ovarian cancer is the lack of standardized treatment protocols, with Current research aims to mitigate these toxicities by investigating alter-
significant variability in chemotherapy agents, perfusion temperatures, native drug delivery systems, including nanoparticle- and liposome-
and treatment durations. These inconsistencies impede protocol based formulations, which may enhance targeted peritoneal
optimization and complicate the comparison of outcomes across chemotherapy delivery while minimizing systemic exposure [27,36].
studies. Establishing standardized parameters is essential to enhance Moreover, optimizing postoperative care and quality of life is critical
reproducibility and support evidence-based clinical decision-making to reducing HIPEC-associated morbidity. Implementation of enhanced
[25,26]. recovery after surgery (ERAS) protocols, advanced multimodal pain
Cisplatin and carboplatin remain the most commonly used chemo- management, and vigilant monitoring of renal and gastrointestinal
therapeutic agents in HIPEC due to their proven efficacy; however, al- function are essential strategies to improve recovery outcomes
ternative agents such as paclitaxel and mitomycin C may provide [36,37]. The identification and validation of biomarkers for early detec-
improved tumor penetration and potentially more favorable toxicity tion of complications could further facilitate prompt intervention,
profiles [27]. Precise temperature control during HIPEC is critical to thereby decreasing postoperative morbidity rates [36].
maximize therapeutic efficacy. Advances in temperature regulation
and real-time monitoring technologies hold promise in minimizing 2.4. Expanding access and cost-effectiveness
risks associated with under-heating (leading to suboptimal drug deliv-
ery) or overheating, which increases toxicity [21–23]. The high cost and resource-intensive nature of HIPEC pose signifi-
Moreover, the development of personalized HIPEC regimens, guided cant barriers to its widespread implementation, particularly in low-
by the molecular and genetic profiling of individual tumors, could fur- resource settings. As evidence on HIPEC accrues, cost-effectiveness
ther optimize treatment efficacy while reducing adverse effects, repre- analyses will be critical to define its role in ovarian cancer management.
senting a promising avenue for future research and clinical application Long-term data on survival benefits and recurrence reduction are essen-
[27]. tial to justify the upfront financial investment associated with this
procedure [36]. Additionally, improving resource allocation through
2.1. Exploring combination therapies with HIPEC the establishment of dedicated HIPEC centers of excellence and foster-
ing interinstitutional collaboration may help mitigate disparities in
HIPEC may derive significant benefit from synergistic combinations access [27,36]. Furthermore, standardized training programs and proto-
with other therapeutic modalities, including immunotherapy, targeted col development are imperative to ensure safe and effective delivery of
agents, and gene therapy, to enhance patient outcomes. Immune check- HIPEC across diverse clinical settings, thereby expanding availability of
point inhibitors such as pembrolizumab and nivolumab have demon- this promising treatment to a broader patient population. The future
strated activity in ovarian cancer, and their combination with HIPEC of HIPEC in ovarian cancer is being shaped by ongoing clinical trials
could potentiate immune-mediated clearance of residual tumor cells aimed at refining its indications and maximizing its therapeutic benefit.
[27–29]. The hyperthermic environment during HIPEC may further Table 3 summarizes key active studies. Notable trials such as

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G. Bogani, A. Fagotti, V. Chiantera et al. Gynecologic Oncology 200 (2025) 161–168

Table 3
Main ongoing phase III trials testing HIPEC in ovarian cancer:

Trial Name Phase Population Setting Objective Key Findings

CHIPPI Phase Stage III/IV ovarian, peritoneal, or fallopian Primary and interval Evaluate HIPEC's impact on Assessing the role of HIPEC in primary
(NCT03842982) III tube cancer (n = 362) debulking surgery OS and PFS and interval debulking surgery
ENGOT-ov52 / Phase Newly diagnosed stage III epithelial ovarian Primary cytoreduction Evaluate HIPEC's impact on Expected results to clarify role of HIPEC in
OVHIPEC-2 III cancer (n = 538) + HIPEC OS and PFS upfront treatment.
(NCT03772028)
GOG-3068 Phase Stage III/IV ovarian, peritoneal, or fallopian Interval cytoreduction Compare HIPEC + niraparib Focuses on maintenance strategies
HOTT III tube cancer (n = 230) + HIPEC maintenance therapy post-HIPEC.
(NCT05659381)
KOV-HIPEC-02 Phase Platinum-resistant ovarian cancer (n = 140) Recurrent disease HIPEC plus chemotherapy vs. Assessing the role of HIPEC in
(NCT05316181) III chemotherapy platinum-resistant setting
KOV-HIPEC-04 Phase Primary epithelial ovarian cancer Interval cytoreduction Assess HIPEC efficacy in Aims to refine neoadjuvant therapy
(NCT05827523) III post-neoadjuvant chemotherapy (n = 520) + HIPEC reducing recurrence integration.

Abbreviation: HIPEC, Hyperthermic intraperitoneal chemotherapy; OS, overall survival; PFS, progression-free survival.

OVHIPEC-2, GOG-3068 (HOTT), and KOV-HIPEC-04 are investigating significant barriers to its widespread adoption, particularly in low-
various aspects of HIPEC, including the efficacy of different chemother- resource settings. Rigorous cost-effectiveness analyses and strategic re-
apeutic agents and optimization of treatment protocols. OVHIPEC-2, a source allocation, including the establishment of specialized centers,
phase III randomized trial, is evaluating the impact of HIPEC combined will be vital for broader implementation. As ongoing clinical trials eluci-
with cytoreductive surgery on progression-free and overall survival in date optimal HIPEC protocols and patient populations, this therapeutic
advanced ovarian cancer. Similarly, GOG-3068 (HOTT) examines the approach is poised to assume a central role in the multidisciplinary
addition of HIPEC to standard chemotherapy in recurrent or metastatic management of advanced and recurrent ovarian cancer, ultimately im-
disease, assessing improvements in clinical outcomes. KOV-HIPEC-04 proving survival outcomes and quality of life for affected patients.
focuses on patients with platinum-sensitive ovarian cancer, testing
whether HIPEC can prolong survival compared to systemic chemother- CRediT authorship contribution statement
apy alone. These and other studies will provide critical data on the
safety, efficacy, and optimal integration of HIPEC into ovarian cancer Giorgio Bogani: Writing – review & editing, Writing – original draft,
treatment algorithms, addressing key questions regarding patient selec- Visualization, Validation, Formal analysis, Data curation, Conceptualiza-
tion, chemotherapy regimens, and long-term benefits. As these trials tion. Anna Fagotti: Writing – review & editing, Writing – original draft,
mature, they are expected to facilitate the development of standardized Visualization, Validation, Methodology, Investigation, Data curation,
protocols and clarify the therapeutic role of HIPEC in ovarian cancer care Conceptualization. Vito Chiantera: Writing – review & editing, Writing
[31]. – original draft, Visualization, Project administration, Formal analysis,
Data curation, Conceptualization. Pierandrea De Iaco: Writing – review
3. Conclusions & editing, Writing – original draft, Visualization, Project administration,
Data curation, Conceptualization. Enrico Vizza: Writing – review &
HIPEC represents a promising therapeutic modality for ovarian can- editing, Writing – original draft, Visualization, Validation, Supervision,
cer, particularly in patients with advanced-stage disease or peritoneal Data curation, Conceptualization. Paolo Scollo: Writing – review &
carcinomatosis. Despite its potential benefits, challenges persist in stan- editing, Writing – original draft, Visualization, Validation, Supervision,
dardizing treatment protocols, optimizing chemotherapy regimens, and Software, Resources, Investigation, Formal analysis, Data curation,
refining patient selection criteria. Current evidence indicates that HIPEC Conceptualization. Marco Petrillo: Writing – review & editing, Writing
combined with cytoreductive surgery can improve progression-free and – original draft, Visualization, Validation, Project administration, Meth-
overall survival, though its efficacy is influenced by factors such as the odology, Data curation, Conceptualization. Andrea Giannini: Writing –
choice of chemotherapeutic agents, temperature control, and appropri- review & editing, Writing – original draft, Visualization, Validation,
ate patient selection. Notably, positive outcomes have been reported Supervision, Software, Methodology, Data curation, Conceptualization.
primarily in patients who demonstrate responsiveness to platinum- Violante Di Donato: Writing – review & editing, Writing – original
based chemotherapy. draft, Visualization, Validation, Supervision, Project administration, For-
The future of HIPEC in ovarian cancer management hinges on several mal analysis, Data curation, Conceptualization. Francesco Raspagliesi:
key developments. Standardization of treatment parameters (including Writing – review & editing, Writing – original draft, Visualization, Vali-
chemotherapy agents, thermal regulation, and perfusion duration) will dation, Formal analysis, Data curation, Conceptualization. Giuseppe
be essential to achieve consistent clinical outcomes and guide practice. Vizzielli: Writing – review & editing, Writing – original draft, Validation,
The exploration of combination strategies, notably integrating HIPEC Supervision, Investigation, Data curation, Conceptualization.
with immunotherapy, targeted agents, and gene therapies, offers con-
siderable potential to enhance antitumor efficacy by addressing tumor Funding
heterogeneity and resistance mechanisms. Furthermore, personalized
treatment approaches based on molecular profiling may optimize None.
therapeutic responses by tailoring interventions to individual tumor
biology. Optimizing patient selection through predictive biomarkers Declaration of competing interest
and advanced imaging modalities, such as intraoperative fluorescence
guidance, will be critical to maximize HIPEC's benefits. Advances in None.
surgical techniques, including robotic-assisted cytoreduction, may fur-
ther improve precision, minimize invasiveness, and enhance treatment References
outcomes [38–40].
[1] J.A. Ledermann, X. Matias-Guiu, F. Amant, et al., ESGO-ESMO-ESP consensus confer-
Efforts to minimize HIPEC-related toxicity and enhance postopera- ence recommendations on ovarian cancer: pathology and molecular biology and
tive recovery are essential to improve its safety profile and patient toler- early, advanced and recurrent disease, Ann. Oncol. 35 (3) (2024 Mar) 248–266,
ability. However, the high costs and resource demands of HIPEC remain doi:10.1016/[Link].2023.11.015 Epub 2024 Feb 1. PMID: 38307807.

167
G. Bogani, A. Fagotti, V. Chiantera et al. Gynecologic Oncology 200 (2025) 161–168

[2] A. du Bois, A. Reuss, E. Pujade-Lauraine, P. Harter, I. Ray-Coquard, J. Pfisterer, Role of [21] F. Coccolini, L. Campanati, F. Catena, et al., Hyperthermic intraperitoneal chemother-
surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a com- apy with cisplatin and paclitaxel in advanced ovarian cancer: a multicenter prospec-
bined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials: tive observational study, J. Gynecol. Oncol. 26 (1) (2015 Jan) 54–61, doi:10.3802/
by the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe jgo.2015.26.1.54 Epub 2014 Nov 3. PMID: 25376916; PMCID: PMC4302286.
Ovarialkarzinom (AGO-OVAR) and the Groupe d’Investigateurs Nationaux pour les [22] G. Grosso, D. Rossetti, F. Coccolini, G. Bogani, L. Ansaloni, L. Frigerio, Intraperitoneal
etudes des cancers de l’Ovaire (GINECO), Cancer 115 (6) (2009 Mar 15) chemotherapy in advanced epithelial ovarian cancer: a survey, Arch. Gynecol.
1234–1244, doi:10.1002/cncr.24149 Erratum in: Cancer. 2024 Sep 1;130(17): Obstet. 290 (3) (2014 Sep) 425–434, doi:10.1007/s00404-014-3252-2 Epub 2014
3043–3045. doi:10.1002/cncr.35344. (PMID: 19189349). May 21. PMID: 24845970.
[3] P. Harter, M. Hahmann, H.J. Lueck, et al., Surgery for recurrent ovarian cancer: role of [23] L. Ansaloni, F. Coccolini, L. Morosi, et al., Pharmacokinetics of concomitant cisplatin
peritoneal carcinomatosis: exploratory analysis of the DESKTOP I trial about risk fac- and paclitaxel administered by hyperthermic intraperitoneal chemotherapy to pa-
tors, surgical implications, and prognostic value of peritoneal carcinomatosis, Ann. tients with peritoneal carcinomatosis from epithelial ovarian cancer, Br. J. Cancer
Surg. Oncol. 16 (5) (2009 May) 1324–1330, doi:10.1245/s10434-009-0357-0 Epub 112 (2) (2015 Jan 20) 306–312, doi:10.1038/bjc.2014.602 Epub 2014 Dec 2.
2009 Feb 19. PMID: 19225844. PMID: 25461804; PMCID: PMC4453456.
[4] P. Harter, J. Sehouli, I. Vergote, et al., Randomized trial of Cytoreductive surgery for [24] O. Zivanovic, A. Abramian, M. Kullmann, et al., HIPEC ROC I: a phase I study of cis-
relapsed ovarian Cancer, N. Engl. J. Med. 385 (23) (2021 Dec 2) 2123–2131, doi: platin administered as hyperthermic intraoperative intraperitoneal chemoperfusion
10.1056/NEJMoa2103294 Erratum in: N. Engl. J. Med. 2022 Feb 17;386(7):704. followed by postoperative intravenous platinum-based chemotherapy in patients
doi:10.1056/NEJMx220002. (PMID: 34874631). with platinum-sensitive recurrent epithelial ovarian cancer, Int. J. Cancer 136 (3)
[5] W.J. van Driel, S.N. Koole, K. Sikorska, et al., Hyperthermic intraperitoneal chemo- (2015 Feb 1) 699–708, doi:10.1002/ijc.29011 Epub 2014 Jun 17. PMID: 24895230.
therapy in ovarian Cancer, N. Engl. J. Med. 378 (3) (2018 Jan 18) 230–240, doi:10. [25] P.H. Sugarbaker, Review of options to traditional HIPEC for prevention and treat-
1056/NEJMoa1708618 (PMID: 29342393). ment of peritoneal metastases, J. Surg. Oncol. (2024 Oct 13), doi:10.1002/jso.
[6] S.L. Aronson, M. Lopez-Yurda, S.N. Koole, et al., Cytoreductive surgery with or with- 27913 (Epub ahead of print. PMID: 39400331).
out hyperthermic intraperitoneal chemotherapy in patients with advanced ovarian [26] P.H. Sugarbaker, O.A. Stuart, HIPEC plus EPIC paclitaxel for maximal perioperative
cancer (OVHIPEC-1): final survival analysis of a randomised, controlled, phase 3 treatments of advanced epithelial ovarian cancer. Long-term results of a pilot
trial, Lancet Oncol. 24 (10) (2023 Oct) 1109–1118, doi:10.1016/S1470-2045(23) study, Surg. Oncol. 35 (2020 Dec) 441–446, doi:10.1016/[Link].2020.09.019
00396-0 Epub 2023 Sep 11. PMID: 37708912. Epub 2020 Sep 28. PMID: 33039850.
[7] M.C. Lim, S.J. Chang, B. Park, et al., Survival after Hyperthermic intraperitoneal che- [27] L. Della Corte, C. Conte, M. Palumbo, et al., Hyperthermic intraperitoneal chemother-
motherapy and primary or interval Cytoreductive surgery in ovarian Cancer: a ran- apy (HIPEC): new approaches and controversies on the treatment of advanced epi-
domized clinical trial, JAMA Surg. 157 (5) (2022 May 1) 374–383, doi:10.1001/ thelial ovarian Cancer-systematic review and Meta-analysis, J. Clin. Med. 12 (22)
jamasurg.2022.0143 PMID: 35262624; PMCID: PMC8908225. (2023 Nov 9) 7012, doi:10.3390/jcm12227012 PMID: 38002626; PMCID:
[8] A. Fagotti, B. Costantini, F. Fanfani, et al., Hyperthermic intraperitoneal chemother- PMC10672052.
apy in platinum-sensitive recurrent ovarian Cancer: a randomized trial on survival [28] M.F. Wu, X.Y. Cheng, D.Y. Wang, et al., Determining the maximum tolerated dose of
evaluation (HORSE; MITO-18), J. Clin. Oncol. (2024 Nov 21), doi:10.1200/JCO.24. paclitaxel combined with fixed dose of cisplatin for hyperthermic intraperitoneal
00686 JCO2400686. (Epub ahead of print. PMID: 39571127). chemotherapy in ovarian cancer: a multicenter phase I trial, Gynecol. Oncol. 181
[9] J.M. Classe, P. Meeus, D. Hudry, et al., Hyperthermic intraperitoneal chemotherapy (2024 Feb) 125–132, doi:10.1016/[Link].2023.12.019 Epub 2023 Dec 30. PMID:
for recurrent ovarian cancer (CHIPOR): a randomised, open-label, phase 3 trial, Lan- 38159362.
cet Oncol. 25 (12) (2024 Dec) 1551–1562, doi:10.1016/S1470-2045(24)00531-X [29] Z.Y. You, M.F. Wu, H. Li, et al., A phase I dose-finding trial of hyperthermic intraper-
Epub 2024 Nov 14. PMID: 39549720. itoneal docetaxel combined with cisplatin in patients with advanced-stage ovarian
[10] Spiliotis J, Halkia E, Lianos E, Kalantzi N, Grivas A, Efstathiou E, Giassas S. cancer, J. Gynecol. Oncol. 35 (1) (2024 Jan) e1, doi:10.3802/jgo.2024.35.e1 Epub
Cytoreductive surgery and HIPEC in recurrent epithelial ovarian cancer: a prospec- 2023 Jul 5. PMID: 37477105; PMCID: PMC10792218.
tive randomized phase III study. Ann. Surg. Oncol. 2015 May;22(5):1570–5. doi:10. [30] P. Corbaux, G. Freyer, O. Glehen, et al., Intraperitoneal Nivolumab after Debulking
1245/s10434-014-4157-9. Epub 2014 Nov 13. PMID: 25391263. surgery and Hyperthermic intraperitoneal chemotherapy in advanced ovarian Can-
[11] P. Villarejo Campos, S. Sánchez García, et al., Paclitaxel as HIPEC-drug after surgical cer: a phase I study with expansion cohort, Clin. Cancer Res. 30 (16) (2024 Aug 15)
Cytoreduction for ovarian peritoneal metastases: a randomized phase III clinical 3438–3446, doi:10.1158/[Link]-24-0507 (PMID: 38819408).
trial (HIPECOVA), Curr. Oncol. 31 (2) (2024 Jan 24) 660–671, doi:10.3390/ [31] NIH National Library of Medicine. [Link], 2025, Available at: https://
curroncol31020048 PMID: 38392042; PMCID: PMC10888026. [Link]/search?cond=Ovarian%20Cancer&term=HIPEC Accessed
[12] C.C.P. Antonio, G.G. Alida, G.G. Elena, et al., Cytoreductive surgery with or without January 2.
HIPEC after neoadjuvant chemotherapy in ovarian Cancer: a phase 3 clinical trial, [32] R. Solidoro, A. Centonze, M. Miciaccia, et al., Fluorescent imaging probes for in vivo
Ann. Surg. Oncol. 29 (4) (2022 Apr) 2617–2625, doi:10.1245/s10434-021-11087-7 ovarian cancer targeted detection and surgery, Med. Res. Rev. 44 (4) (2024 Jul)
Epub 2021 Nov 23. PMID: 34812982. 1800–1866, doi:10.1002/med.22027 Epub 2024 Feb 17. PMID: 38367227.
[13] M.J. Page, J.E. McKenzie, P.M. Bossuyt, et al., The PRISMA 2020 statement: an up- [33] J.A. Rauh-Hain, A. Melamed, R. Pareja, et al., Laparoscopic Cytoreduction after neoad-
dated guideline for reporting systematic reviews, BMJ 29 (372) (2021 Mar) n71, juvant chemotherapy in high-grade epithelial ovarian Cancer: a LANCE randomized
doi:10.1136/bmj.n71 PMID: 33782057; PMCID: PMC8005924. clinical trial, JAMA Netw. Open 7 (11) (2024 Nov 4) e2446325, doi:10.1001/
[14] Z. Lei, Y. Wang, J. Wang, et al., Evaluation of Cytoreductive surgery with or without jamanetworkopen.2024.46325 PMID: 39570589; PMCID: PMC11582931.
Hyperthermic intraperitoneal chemotherapy for stage III epithelial ovarian Cancer, [34] C.Y. Cho, J. Veerapong, J.M. Baumgartner, J.D. Murphy, A.M. Lowy, K.J. Kelly, Laparo-
JAMA Netw. Open 3 (8) (2020 Aug 3) e2013940, doi:10.1001/jamanetworkopen. scopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: a
2020.13940 PMID: 32840622; PMCID: PMC7448829. prospective clinical trial and comparative analysis, Surg. Endosc. 37 (7) (2023 Jul)
[15] M. Karanikas, K. Kofina, D. Kyziridis, G. Trypsianis, A. Kalakonas, A.A. Tentes, HIPEC 5644–5651, doi:10.1007/s00464-022-09589-w (Epub 2022 Dec 7. PMID:
as up-front treatment in locally advanced ovarian Cancer, Cancers (Basel) 16 (20) 36477643; PMCID: PMC10322763).
(2024 Oct 16) 3500, doi:10.3390/cancers16203500 PMID: 39456594; PMCID: [35] A.M. Praiss, Q. Zhou, A. Iasonos, L. Moukarzel, K. Dessources, K. Soldan, et al., Mor-
PMC11505607. bidity after secondary cytoreductive surgery with or without hyperthermic intra-
[16] V. Ghirardi, F. De Felice, M. D’Indinosante, F. Bernardini, M.T. Giudice, A. Fagotti, peritoneal chemotherapy for ovarian cancer: An analysis of a randomized phase II
et al., Hyperthermic intraperitoneal chemotherapy (HIPEC) after primary debulking trial, Gynecol. Oncol. 171 (2023 Apr) 23–30, doi:10.1016/[Link].2023.02.003
surgery in advanced epithelial ovarian cancer: is BRCA mutational status making the Epub 2023 Feb 16. PMID: 36804618; PMCID: PMC10206782.
difference? Cancer Treat Res Commun. 31 (2022) 100518, doi:10.1016/[Link].2022. [36] S. Kusamura, A. Bhatt, K. van Der Speeten, et al., Review of 2022 PSOGI/RENAPE con-
100518 Epub 2022 Jan 14. PMID: 35065323. sensus on HIPEC, J. Surg. Oncol. (2024 Sep 16)doi:10.1002/jso.27885 (Epub ahead of
[17] J.H. Kim, S.Y. Chun, D.E. Lee, et al., Cost-effectiveness of hyperthermic intraperitoneal print. PMID: 39285659).
chemotherapy following interval cytoreductive surgery for stage III-IV ovarian can- [37] J.H. Kim, D.E. Lee, Y. Lee, H.I. Ha, Y.J. Chang, S.J. Chang, et al., Quality of life outcomes
cer from a randomized controlled phase III trial in Korea (KOV-HIPEC-01), Gynecol. from the randomized trial of hyperthermic intraperitoneal chemotherapy following
Oncol. 170 (2023 Mar) 19–24, doi:10.1016/[Link].2022.12.021 Epub 2023 Jan 4. cytoreductive surgery for primary ovarian cancer (KOV-HIPEC-01), J. Gynecol.
PMID: 36608383. Oncol. 33 (4) (2022 Jul) e54, doi:10.3802/jgo.2022.33.e54 Epub 2022 May 31.
[18] T.P. Batista, V.C.G. Carneiro, R. Tancredi, et al., A phase 2 trial of short-course Hyper- PMID: 35712968; PMCID: PMC9250851.
thermic IntraPeritoneal chemotherapy (HIPEC) at interval cytoreductive surgery [38] F.A. Ferrari, M. Ceccaroni, G. Scambia, et al., Enhancing surgical precision in ovarian
(iCRS) for advanced ovarian cancer, Rev. Col. Bras. Cir. 28 (49) (2022 Feb) cancer with FRα-fluorescence-guided surgery, Eur. J. Surg. Oncol. 51 (8) (2025 May
e20223135, doi:10.1590/0100-6991e-20223135 PMID: 35239855; PMCID: 2) 110120, doi:10.1016/[Link].2025.110120 (Epub ahead of print. PMID: 40344696).
PMC10578806. [39] P. Aurello, M. Pace, M. Goglia, et al., Enhancing surgical education through artificial
[19] S.N. Koole, P.C. Schouten, J. Hauke, et al., Effect of HIPEC according to HRD/BRCAwt intelligence in the era of digital surgery, Am. Surg. 2 (2025 Jun), doi:10.1177/
genomic profile in stage III ovarian cancer: results from the phase III OVHIPEC 00031348251346539 31348251346539. Epub ahead of print. PMID: 40454799.
trial, Int. J. Cancer 151 (8) (2022 Oct 15) 1394–1404, doi:10.1002/ijc.34124 Epub [40] S. González Sánchez, J. García Fernández, P.A. Cascales-Campos, et al., Interval
2022 Jun 4. PMID: 35583992. Cytoreductive surgery and cisplatin- or paclitaxel-based HIPEC for advanced
[20] V. Ghirardi, R. Trozzi, F.R. Scanu, et al., Expanding the use of HIPEC in ovarian Cancer ovarian Cancer, JAMA Netw. Open 8 (6) (2025 Jun 2), e2517676, doi:10.1001/
at time of interval Debulking surgery to FIGO stage IV and after 6 cycles of neoadju- jamanetworkopen.2025.17676 (PMID: 40569595).
vant chemotherapy: a prospective analysis on perioperative and oncologic
outcomes, Ann. Surg. Oncol. 31 (5) (2024 May) 3350–3360, doi:10.1245/s10434-
024-15042-0 (Epub 2024 Feb 27. PMID: 38411761; PMCID: PMC10997530).

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