Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial

Quénet, François; Élias, Dominique; Roca, Lise; Goèré, Diane; Ghouti, Laurent; Pocard, Marc; Facy, Olivier; Arvieux, C.; Lorimier, G.; Pezet, Denis; Marchal, Frédéric; Loi, Valeria; Méeus, Pierre; Juzyna, Béata; Forges, Hélène de; Paineau, J; Gléhen, Olivier; Mariani, Pascale; Brigand, Cécile; Béréder, Jean-Marc; Msika, Simon; Portier, G.; Rat, Patrick

doi:10.1016/s1470-2045(20)30599-4

Cited by 538 publications

(466 citation statements)

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“…Assuming that the rate of DLS is inversely related to the incomplete and open-close rate, the potential benefit of additional MRI staging could nonetheless become apparent. Furthermore, the benefit of Oxaliplatin-based HIPEC in the combined CRS-HIPEC procedure has recently come under debate following the results of the PRODIGE-7 trial [11]. However, this study reinforced the notion that complete cytoreduction is the most determinant factor of survival, a finding that underlines how important it is to safely and effectively select those patients for whom a complete CRS is feasible.…”

Section: Discussionmentioning

confidence: 63%

“…Two trials are ongoing in the Netherlands exploring novel palliative strategies for patients with extensive CRCPM, namely the use of concomitant intraperitoneal and systemic chemotherapy (INTERACT) and repetitive electrostatic pressurized intraperitoneal aerosol chemotherapy with oxaliplatin (ePIPAC) [27,28]. Twenty-three percent of candidates for the PRODIGE-7 trial were excluded at laparotomy due to the extent of PM, liver metastases or non-resectable disease [11]. Other studies have reported incomplete CRS rates of around 20-40%, when selecting patients suitable for CRS-HIPEC with CT [6,7,10].…”

Section: Discussionmentioning

confidence: 99%

“…Currently, assessment of the extent and localization of peritoneal metastases, to determine whether a complete CRS is feasible, is ultimately performed during laparotomy. Open-close or incomplete procedures have been reported to occur in 20 to 40% of cases [6][7][8][9][10][11]. However, best practice would be to avoid futile, invasive and costly surgical procedures in patients for whom CRS-HIPEC is not feasible and/or unlikely to improve survival.…”

Section: Introductionmentioning

confidence: 99%

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Dedicated MRI staging versus surgical staging of peritoneal metastases in colorectal cancer patients considered for CRS-HIPEC; the DISCO randomized multicenter trial

et al. 2021

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Background Selecting patients with peritoneal metastases from colorectal cancer (CRCPM) who might benefit from cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is challenging. Computed tomography generally underestimates the peritoneal tumor load. Diagnostic laparoscopy is often used to determine whether patients are amenable for surgery. Magnetic resonance imaging (MRI) has shown to be accurate in predicting completeness of CRS. The aim of this study is to determine whether MRI can effectively reduce the need for surgical staging. Methods The study is designed as a multicenter randomized controlled trial (RCT) of colorectal cancer patients who are deemed eligible for CRS-HIPEC after conventional CT staging. Patients are randomly assigned to either MRI based staging (arm A) or to standard surgical staging with or without laparoscopy (arm B). In arm A, MRI assessment will determine whether patients are eligible for CRS-HIPEC. In borderline cases, an additional diagnostic laparoscopy is advised. The primary outcome is the number of unnecessary surgical procedures in both arms defined as: all surgeries in patients with definitely inoperable disease (PCI > 24) or explorative surgeries in patients with limited disease (PCI < 15). Secondary outcomes include correlations between surgical findings and MRI findings, cost-effectiveness, and quality of life (QOL) analysis. Conclusion This randomized trial determines whether MRI can effectively replace surgical staging in patients with CRCPM considered for CRS-HIPEC. Trial registration Registered in the clinical trials registry of U.S. National Library of Medicine under NCT04231175.

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Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dedicated MRI staging versus surgical staging of peritoneal metastases in colorectal cancer patients considered for CRS-HIPEC; the DISCO randomized multicenter trial

et al. 2021

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“…With regards to the chemotherapy regimen used in this study, the results of the recently published PRODIGE-7 trial may question the intraperitoneal use of oxaliplatin (combined with 5-fluorouracil and leucovorin) in patients with CPM. 37 However, in contrast with PRODIGE-7, patients in the present study are either systemic therapynaïve or had undergone a mandatory 6-month wash-out period of systemic therapy. As a result, the previously untreated patients in this study may be more sensitive to intraperitoneal oxaliplatin than patients in the PRODIGE-7 trial.…”

Section: Discussionmentioning

confidence: 93%

First-line palliative systemic therapy alternated with electrostatic pressurised intraperitoneal aerosol chemotherapy (oxaliplatin) for isolated unresectable colorectal peritoneal metastases: protocol of a multicentre, single-arm, phase II study (CRC-PIPAC-II)

et al. 2021

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IntroductionDespite its increasing use, first-line palliative systemic therapy alternated with electrostatic pressurised intraperitoneal aerosol chemotherapy with oxaliplatin (ePIPAC-OX), hereinafter referred to as first-line bidirectional therapy, has never been prospectively investigated in patients with colorectal peritoneal metastases (CPM). As a first step to address this evidence gap, the present study aims to assess the safety, feasibility, antitumour activity, patient-reported outcomes, costs and systemic pharmacokinetics of first-line bidirectional therapy in patients with isolated unresectable CPM.Methods and analysisIn this single-arm, phase II study in two Dutch tertiary referral centres, 20 patients are enrolled. Key eligibility criteria are a good performance status, pathologically proven isolated unresectable CPM, no previous palliative systemic therapy for colorectal cancer, no (neo)adjuvant systemic therapy ≤6 months prior to enrolment and no previous pressurised intraperitoneal aerosol chemotherapy (PIPAC). Patients receive three cycles of bidirectional therapy. Each cycle consists of 6 weeks first-line palliative systemic therapy at the medical oncologists’ decision (CAPOX-bevacizumab, FOLFOX-bevacizumab, FOLFIRI-bevacizumab or FOLFOXIRI-bevacizumab) followed by ePIPAC-OX (92 mg/m2) with an intraoperative bolus of intravenous leucovorin (20 mg/m2) and 5-fluorouracil (400 mg/m2). Study treatment ends after the third ePIPAC-OX. The primary outcome is the number of patients with—and procedures leading to—grade ≥3 adverse events (Common Terminology Criteria for Adverse Events V.5.0) up to 4 weeks after the last procedure. Key secondary outcomes include the number of bidirectional cycles in each patient, treatment-related characteristics, grade ≤2 adverse events, tumour response (histopathological, cytological, radiological, biochemical, macroscopic and ascites), patient-reported outcomes, systemic pharmacokinetics of oxaliplatin, costs, progression-free survival and overall survival.Ethics and disseminationThis study is approved by the Dutch competent authority, a medical ethics committee and the institutional review boards of both study centres. Results will be submitted for publication in peer-reviewed medical journals and presented to patients and healthcare professionals.Trial registration numberNL8303.

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“…Even if peritoneal carcinomatosis is a poor prognostic index, its responsiveness to chemotherapy has been documented [35,36]. A debate is ongoing regarding systemic and intraperitoneal chemotherapy [36,37], with the data from the Prodige 7 trial suggesting similar results between the two [38].…”

Section: Discussionmentioning

confidence: 99%

Hepatic and Extrahepatic Colorectal Metastases Have Discordant Responses to Systemic Therapy. Pathology Data from Patients Undergoing Simultaneous Resection of Multiple Tumor Sites

Viganò

Corleone

Darwish

et al. 2021

Cancers

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Background: Systemic therapy is the standard treatment for patients with hepatic and extrahepatic colorectal metastases. It is assumed to have the same effectiveness on all disease foci, independent of the involved organ. The present study aims to compare the response rates of hepatic and extrahepatic metastases to systemic therapy. Methods: All consecutive patients undergoing simultaneous resection of hepatic and extrahepatic metastases from colorectal cancer after oxaliplatin- and/or irinotecan-based preoperative chemotherapy were analyzed. All specimens were reviewed. Pathological response to chemotherapy was classified according to tumor regression grade (TRG). Results: We analyzed 45 patients undergoing resection of 134 hepatic and 72 extrahepatic metastases. Lung and lymph node metastases had lower response rates to chemotherapy than liver metastases (TRG 4–5 95% and 100% vs. 67%, p = 0.008, and p = 0.006). Peritoneal metastases had a higher pathological response rate than liver metastases (TRG 1–3 66% vs. 33%, p < 0.001) and non-hepatic non-peritoneal metastases (3%, p < 0.001). Metastases site was an independent predictor of pathological response to systemic therapy. Conclusions: Response to chemotherapy of distant metastases from colorectal cancer varies in different organs. Systemic treatment is highly effective for peritoneal metastases, more so than liver metastases, while it has a very poor impact on lung and lymph node metastases.

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Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial

Cited by 538 publications

References 31 publications

Dedicated MRI staging versus surgical staging of peritoneal metastases in colorectal cancer patients considered for CRS-HIPEC; the DISCO randomized multicenter trial

Dedicated MRI staging versus surgical staging of peritoneal metastases in colorectal cancer patients considered for CRS-HIPEC; the DISCO randomized multicenter trial

First-line palliative systemic therapy alternated with electrostatic pressurised intraperitoneal aerosol chemotherapy (oxaliplatin) for isolated unresectable colorectal peritoneal metastases: protocol of a multicentre, single-arm, phase II study (CRC-PIPAC-II)

Hepatic and Extrahepatic Colorectal Metastases Have Discordant Responses to Systemic Therapy. Pathology Data from Patients Undergoing Simultaneous Resection of Multiple Tumor Sites

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