CC BY-NC-ND 4.0 · South Asian J Cancer 2024; 13(04): 267-273
DOI: 10.1055/s-0045-1802982
Review Article
Multimodality

Current Status of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Colorectal Cancer (CRC)

1   Department of Surgical Oncology, Aster DM Healthcare, Bengaluru, Karnataka, India
,
2   Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
,
Deep Goyal
3   Department of Surgical Gastroenterology, BLK-Max Super Speciality Hospital, New Delhi, India
,
Saumitra Rawat
4   Department of Surgical Gastroenterology, Sir Ganga Ram Hospital (SGRH), New Delhi, India
,
Shyam Aggarwal
5   Department of Medical Oncology, Sir Ganga Ram Hospital, New Delhi, India
,
C. Selvasekar
6   Clinical Services & Specialist Surgery, The Christie NHS Foundation Trust, Manchester, United Kingdom
,
Purvish M. Parikh
7   Department of Clinical Hematology, Sri Ram Cancer Center, Mahatma Gandhi University of Medical Sciences and Technology, Jaipur, Rajasthan, India
› Institutsangaben

Abstract

Accounting for 8.7% of global cancer deaths, colorectal cancer (CRC) is one of the leading causes of cancer-related mortality. Cytoreduction surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is part of a multimodal strategy for managing CRC. HIPEC is designed to target residual microscopic disease using heated chemotherapy. There are several techniques including the open abdomen “coliseum” technique, which uses a silastic sheet to create a perfusion chamber and allows for manipulation of contents; whereas the closed abdomen technique maintains a sterile environment and may involve abdominal wall massage for heat distribution; lastly, the laparoscopic method combines the benefits of both techniques with enhanced drug distribution through laparoscopy. Research has shown that the coliseum technique offers superior heat uniformity, while the laparoscopic method provides optimal distribution with advanced monitoring tools. We examined early trials, procedural variations, and recent clinical research to assess its efficacy.

HIPEC involves the administration of heated chemotherapy directly into the peritoneal cavity after CRS in order to enhance local tumor control and survival. Various regimens that have been explored, including the Sugarbaker, triple dosing, and low dose mitomycin C regimen, report mixed results. The selection of chemotherapy drugs and their efficacy at high temperatures is crucial, with studies yielding mixed results for oxaliplatin and mitomycin C. The advantages of HIPEC, especially with oxaliplatin-based regimens, have been questioned by recent trials such as the PRODIGE 7 study because of problems like chemoresistance and greater postoperative morbidity. On the other hand, HIPEC is still supported by some as a good choice for individuals who are carefully chosen, particularly when combined with other forms of treatment. Despite being widely used in several cancer centers around the world for other pathologies, HIPEC remains a debated treatment option in CRC with peritoneal metastases. Even though the current evidence suggests that it might not provide a statistically meaningful overall survival improvement when compared to CRS alone, it might still be useful in some clinical settings or when combined with well-designed protocols. Thus, the necessity of more research and standardized protocols is paramount.

Determining the role of HIPEC, maximizing patient selection, and contrasting its effectiveness with other intraperitoneal treatments such as pressurized intraperitoneal aerosol chemotherapy and early postoperative intraperitoneal chemotherapy will require ongoing trials and future research. Until clearer evidence emerges, HIPEC should be considered a therapeutic option for selected patients and offered by dedicated, experienced centers and surgical teams.



Publikationsverlauf

Eingereicht: 12. Dezember 2024

Angenommen: 10. Januar 2025

Artikel online veröffentlicht:
14. Februar 2025

© 2025. MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

 
  • References

  • 1 Cancer of the Colon and Rectum - Cancer Stat Facts. SEER. Accessed May 14, 2024 at: https://seer.cancer.gov/statfacts/html/colorect.html
  • 2 Ben Aziz M, Di Napoli R. Hyperthermic Intraperitoneal Chemotherapy. In: StatPearls. StatPearls Publishing; 2024. . Accessed May 14, 2024 at: http://www.ncbi.nlm.nih.gov/books/NBK570563/
  • 3 Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer - PMC. . Accessed May 15, 2024 at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4716024/
  • 4 Coccolini F, Cotte E, Glehen O. et al. Intraperitoneal chemotherapy in advanced gastric cancer. Meta-analysis of randomized trials. Eur J Surg Oncol 2014; 40 (01) 12-26
  • 5 Hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS) in ovarian cancer: A systematic review and meta-analysis - PubMed. Accessed May 15, 2024 at: https://pubmed.ncbi.nlm.nih.gov/26453145/
  • 6 Verwaal VJ, van Ruth S, de Bree E. et al. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol 2003; 21 (20) 3737-3743
  • 7 Elias D, Lefevre JH, Chevalier J. et al. Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol 2009; 27 (05) 681-685
  • 8 Goéré D, Malka D, Tzanis D. et al. Is there a possibility of a cure in patients with colorectal peritoneal carcinomatosis amenable to complete cytoreductive surgery and intraperitoneal chemotherapy?. Ann Surg 2013; 257 (06) 1065-1071
  • 9 Van der Speeten K, Lemoine L, Sugarbaker P. Overview of the optimal perioperative intraperitoneal chemotherapy regimens used in current clinical practice. Pleura Peritoneum 2017; 2 (02) 63-72
  • 10 Dehal A, Smith JJ, Nash GM. Cytoreductive surgery and intraperitoneal chemotherapy: an evidence-based review-past, present and future. J Gastrointest Oncol 2016; 7 (01) 143-157
  • 11 González-Moreno S, González-Bayón LA, Ortega-Pérez G. Hyperthermic intraperitoneal chemotherapy: rationale and technique. World J Gastrointest Oncol 2010; 2 (02) 68-75
  • 12 Cavaliere F, Perri P, Di Filippo F. et al. Treatment of peritoneal carcinomatosis with intent to cure. J Surg Oncol 2000; 74 (01) 41-44
  • 13 Chemohyperthermic peritoneal perfusion for peritoneal dissemination in various intra-abdominal malignancies - PubMed. Accessed May 16, 2024 at: https://pubmed.ncbi.nlm.nih.gov/10421021/
  • 14 Schneebaum S, Arnold MW, Staubus A, Young DC, Dumond D, Martin Jr EW. Intraperitoneal hyperthermic perfusion with mitomycin C for colorectal cancer with peritoneal metastases. Ann Surg Oncol 1996; 3 (01) 44-50
  • 15 Glehen O, Kwiatkowski F, Sugarbaker PH. et al. Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study. J Clin Oncol 2004; 22 (16) 3284-3292
  • 16 Verwaal VJ, Bruin S, Boot H, van Slooten G, van Tinteren H. 8-year follow-up of randomized trial: cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer. Ann Surg Oncol 2008; 15 (09) 2426-2432
  • 17 Solanki SL, Mukherjee S, Agarwal V. et al. Society of Onco-Anaesthesia and Perioperative Care consensus guidelines for perioperative management of patients for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Indian J Anaesth 2019; 63 (12) 972-987
  • 18 Glehen O, Cotte E, Kusamura S. et al. Hyperthermic intraperitoneal chemotherapy: nomenclature and modalities of perfusion. J Surg Oncol 2008; 98 (04) 242-246
  • 19 Elias D, Antoun S, Goharin A, Otmany AE, Puizillout JM, Lasser P. Research on the best chemohyperthermia technique of treatment of peritoneal carcinomatosis after complete resection. Int J Surg Investig 2000; 1 (05) 431-439
  • 20 Lotti M, Capponi MG, Piazzalunga D. et al. Laparoscopic HIPEC: a bridge between open and closed-techniques. J Minim Access Surg 2016; 12 (01) 86-89
  • 21 Yang YC, Wang D, Jin L. et al. Circulating tumor DNA detectable in early- and late-stage colorectal cancer patients. Biosci Rep 2018; 38 (04) BSR20180322
  • 22 El Messaoudi S, Mouliere F, Du Manoir S. et al. Circulating DNA as a strong multimarker prognostic tool for metastatic colorectal cancer patient management care. Clin Cancer Res 2016; 22 (12) 3067-3077
  • 23 Kasi PM, Budde G, Krainock M. et al. Circulating tumor DNA (ctDNA) serial analysis during progression on PD-1 blockade and later CTLA-4 rescue in patients with mismatch repair deficient metastatic colorectal cancer. J Immunother Cancer 2022; 10 (01) e003312
  • 24 Circulating tumor DNA analysis for assessment of recurrence risk, benefit of adjuvant therapy, and early relapse detection after treatment in colorectal cancer patients.—Aalborg University's Research Portal. Accessed June 1, 2024 at: https://vbn.aau.dk/en/publications/circulating-tumor-dna-analysis-for-assessment-of-recurrence-risk-
  • 25 Cremolini C, Rossini D, Dell'Aquila E. et al. Rechallenge for patients with RAS and BRAF wild-type metastatic colorectal cancer with acquired resistance to first-line cetuximab and irinotecan: a phase 2 single-arm clinical trial. JAMA Oncol 2019; 5 (03) 343-350
  • 26 Raza A, Khan AQ, Inchakalody VP. et al. Dynamic liquid biopsy components as predictive and prognostic biomarkers in colorectal cancer. J Exp Clin Cancer Res 2022; 41 (01) 99
  • 27 Zhao PY, Hu SD, Li YX. et al. Clinical efficacy and safety of hyperthermic intraperitoneal chemotherapy in colorectal cancer patients at high risk of peritoneal carcinomatosis: a systematic review and meta-analysis. Front Surg 2020; 7: 590452
  • 28 Yurttas C, Hoffmann G, Tolios A. et al. Systematic review of variations in hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastasis from colorectal cancer. J Clin Med 2018; 7 (12) 567
  • 29 Stamou K, Gouvas N, Pechlivanides G, Xynos E. Primary curative surgery and preemptive or adjuvant hyperthermic peritoneal chemotherapy in colorectal cancer patients at high risk to develop peritoneal carcinomatosis. A systematic review. J Balkan Union Oncol 2018; 23 (05) 1249-1261
  • 30 Cohen L, Alam F, Flood MP. et al. A systematic review of minimally invasive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal malignancy. ANZ J Surg 2024; 94 (7-8): 1324-1332
  • 31 Zhang X, Wu Q, Wei M, Deng X, Gu C, Wang Z. Oxaliplatin versus mitomycin C in HIPEC for peritoneal metastasis from colorectal cancer: a systematic review and meta-analysis of comparative studies. Int J Colorectal Dis 2020; 35 (10) 1831-1839
  • 32 Hompes D, D'Hoore A, Wolthuis A. et al. The use of oxaliplatin or mitomycin C in HIPEC treatment for peritoneal carcinomatosis from colorectal cancer: a comparative study. J Surg Oncol 2014; 109 (06) 527-532
  • 33 Wisselink DD, Braakhuis LLF, Gallo G. et al. Systematic review of published literature on oxaliplatin and mitomycin C as chemotherapeutic agents for hyperthermic intraperitoneal chemotherapy in patients with peritoneal metastases from colorectal cancer. Crit Rev Oncol Hematol 2019; 142: 119-129
  • 34 Quenet F, Elias D, Roca L. et al. A UNICANCER phase III trial of hyperthermic intra-peritoneal chemotherapy (HIPEC) for colorectal peritoneal carcinomatosis (PC): PRODIGE 7. JCO 2018; 36 (18) LBA3503-LBA3503
  • 35 Quénet F, Elias D, Roca L. et al; UNICANCER-GI Group and BIG Renape Group. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 2021; 22 (02) 256-266
  • 36 Kitaguchi D, Park EJ, Baik SH, Sasaki S, Tsukada Y, Ito M. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus R0 resection for resectable colorectal cancer with peritoneal metastases and low peritoneal cancer index scores: a collaborative observational study from Korea and Japan. Int J Surg 2024; 110 (01) 45-52
  • 37 Di Giorgio A, Rotolo S, Cintoni M. et al. The prognostic value of skeletal muscle index on clinical and survival outcomes after cytoreduction and HIPEC for peritoneal metastases from colorectal cancer: a systematic review and meta-analysis. Eur J Surg Oncol 2022; 48 (03) 649-656
  • 38 Lundbech M, Krag AE, Iversen LH, Hvas AM. Postoperative bleeding and venous thromboembolism in colorectal cancer patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: a systematic review and meta-analysis. Int J Colorectal Dis 2022; 37 (01) 17-33
  • 39 Natalucci V, Virgili E, Calcagnoli F. et al. Cancer related anemia: an integrated multitarget approach and lifestyle interventions. Nutrients 2021; 13 (02) 482
  • 40 Mehta SS, Gelli M, Agarwal D, Goéré D. Complications of cytoreductive surgery and HIPEC in the treatment of peritoneal metastases. Indian J Surg Oncol 2016; 7 (02) 225-229
  • 41 Flood MP, Kong JCH, Wilson K. et al. The impact of neoadjuvant chemotherapy on the surgical management of colorectal peritoneal metastases: a systematic review and meta-analysis. Ann Surg Oncol 2022; 29 (11) 6619-6631
  • 42 de Cuba EMV, Kwakman R, Knol DL, Bonjer HJ, Meijer GA, Te Velde EA. Cytoreductive surgery and HIPEC for peritoneal metastases combined with curative treatment of colorectal liver metastases: systematic review of all literature and meta-analysis of observational studies. Cancer Treat Rev 2013; 39 (04) 321-327
  • 43 Cao C, Yan TD, Black D, Morris DL. A systematic review and meta-analysis of cytoreductive surgery with perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis of colorectal origin. Ann Surg Oncol 2009; 16 (08) 2152-2165
  • 44 Narasimhan V, Tan S, Kong J. et al. Prognostic factors influencing survival in patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for isolated colorectal peritoneal metastases: a systematic review and meta-analysis. Colorectal Dis 2020; 22 (11) 1482-1495
  • 45 Hallam S, Tyler R, Price M, Beggs A, Youssef H. Meta-analysis of prognostic factors for patients with colorectal peritoneal metastasis undergoing cytoreductive surgery and heated intraperitoneal chemotherapy. BJS Open 2019; 3 (05) 585-594
  • 46 Tonello M, Cenzi C, Pizzolato E. et al. Systemic chemotherapy in colorectal peritoneal metastases treated with cytoreductive surgery: systematic review and meta-analysis. Cancers (Basel) 2024; 16 (06) 1182
  • 47 Flood MP, Das AA, Soucisse ML. et al. Synchronous liver resection, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy for colorectal liver and peritoneal metastases: a systematic review and meta-analysis. Dis Colon Rectum 2021; 64 (06) 754-764
  • 48 Parikh MS, Johnson P, Romanes JP. et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: a systematic review. Dis Colon Rectum 2022; 65 (01) 16-26
  • 49 Dominic JL, Kannan A, Tara A. et al. Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) for the prevention and control of peritoneal metastasis in patients with gastrointestinal malignancies: a systematic review of randomized controlled trials. EXCLI J 2021; 20: 1328-1345
  • 50 Gurusamy K, Leung J, Vale C. et al. Cytoreductive surgery plus hyperthermic intraoperative peritoneal chemotherapy for people with peritoneal metastases from colorectal, ovarian or gastric origin: a systematic review of randomized controlled trials. World J Surg 2024; 48 (06) 1385-1403
  • 51 Goéré D, Glehen O, Quenet F. et al; BIG-RENAPE group. Second-look surgery plus hyperthermic intraperitoneal chemotherapy versus surveillance in patients at high risk of developing colorectal peritoneal metastases (PROPHYLOCHIP-PRODIGE 15): a randomised, phase 3 study. Lancet Oncol 2020; 21 (09) 1147-1154
  • 52 Klaver CEL, Wisselink DD, Punt CJA. et al; COLOPEC collaborators group. Adjuvant hyperthermic intraperitoneal chemotherapy in patients with locally advanced colon cancer (COLOPEC): a multicentre, open-label, randomised trial. Lancet Gastroenterol Hepatol 2019; 4 (10) 761-770
  • 53 Prabhu A, Brandl A, Wakama S. et al. Effect of oxaliplatin-based chemotherapy on chemosensitivity in patients with peritoneal metastasis from colorectal cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: proof-of-concept study. BJS Open 2021; 5 (02) zraa075
  • 54 Braam HJ, Boerma D, Wiezer MJ, van Ramshorst B. Cytoreductive surgery and HIPEC in treatment of colorectal peritoneal carcinomatosis: experiment or standard care? A survey among oncologic surgeons and medical oncologists. Int J Clin Oncol 2015; 20 (05) 928-934
  • 55 Sommariva A, Tonello M, Coccolini F. et al. Colorectal cancer with peritoneal metastases: the impact of the results of PROPHYLOCHIP, COLOPEC, and PRODIGE 7 trials on peritoneal disease management. Cancers (Basel) 2022; 15 (01) 165
  • 56 Arjona-Sanchez A, Cano-Osuna M, Gutierrez A. et al. 314O Adjuvant hyperthermic intraperitoneal chemotherapy in locally advanced colon cancer (HIPECT4): a randomized phase III study. Ann Oncol 2022; 33: S680