Heated Chemotherapy During Surgery for Abdominal Cancers: What Patients Need to Know

Table of Contents

• Background: Understanding Peritoneal Metastases
• How the Research Was Conducted
• Findings for Gastric Cancer
• Findings for Ovarian Cancer
• Findings for Colorectal Cancer
• What These Results Mean
• Study Limitations
• Patient Recommendations
• Source Information

Background: Understanding Peritoneal Metastases

Peritoneal metastases occur when cancer spreads to the lining of the abdominal cavity (peritoneum). This is a common progression for colorectal, ovarian, and gastric cancers, affecting 8-50% of patients diagnosed with these cancers. Unfortunately, peritoneal metastases typically indicate poorer prognosis than when cancer spreads to other organs like the liver or lungs.

Patients with peritoneal metastases historically faced limited treatment options and median survival ranging from just 6 to 24 months. The standard approach has been systemic chemotherapy (chemotherapy that travels throughout the entire body) either alone or combined with cytoreductive surgery (CRS), which aims to remove all visible cancer deposits.

A more aggressive approach called cytoreductive surgery plus hyperthermic intraoperative peritoneal chemotherapy (CRS + HIPEC) involves surgically removing visible cancer followed by circulating heated chemotherapy drugs directly into the abdominal cavity. The heat (typically 42°C/107.6°F) may enhance chemotherapy effectiveness against any remaining microscopic cancer cells.

This treatment approach carries significant risks, including major complication rates of 10-15% and costs ranging from $20,000 to $80,000 per patient. Given these substantial risks and costs, determining whether HIPEC provides meaningful benefits for patients is critically important.

How the Research Was Conducted

Researchers conducted a systematic review of all available randomized controlled trials (the gold standard in medical research) published through April 14, 2022. They searched multiple medical databases including MEDLINE, EMBASE, and Cochrane Library to identify every relevant study.

The analysis included eight randomized trials involving 955 participants across seven studies (one trial couldn't be included in numerical analysis due to how data was reported). The studies compared different treatment approaches:

• CRS + HIPEC + systemic chemotherapy versus CRS + systemic chemotherapy
• CRS + HIPEC + systemic chemotherapy versus systemic chemotherapy alone

Researchers assessed study quality using rigorous scientific standards (ROB 2.0 tool) and evaluated the certainty of evidence using GRADE methodology. They analyzed data on survival, serious adverse events, quality of life, and time to disease progression.

Most comparisons contained only one trial except for ovarian cancer, which had three trials. This limited the ability to combine results across multiple studies for some cancer types.

Findings for Gastric (Stomach) Cancer

The evidence for gastric cancer peritoneal metastases remains highly uncertain. One trial with 68 participants provided analyzable data, while another trial with 105 participants couldn't be included in the numerical analysis but reported no difference in survival between treatment groups.

For CRS + HIPEC + systemic chemotherapy versus CRS + systemic chemotherapy, the evidence was deemed very low certainty. The estimated effect showed a hazard ratio of 0.38 (95% CI 0.21 to 0.70), suggesting possible reduced mortality with HIPEC, but the high uncertainty means we cannot draw reliable conclusions.

Similarly, serious adverse events showed a risk ratio of 1.25 (95% CI 0.37 to 4.26), indicating possible increased complications with HIPEC, but again with very low certainty evidence.

For CRS + HIPEC + systemic chemotherapy versus systemic chemotherapy alone, only one small trial with 17 participants was available. It suggested HIPEC might decrease mortality (hazard ratio 0.40, 95% CI 0.30 to 0.52), but the very small sample size creates high uncertainty.

Findings for Ovarian Cancer

For women with stage III or greater epithelial ovarian cancer requiring interval cytoreductive surgery (surgery after initial chemotherapy), the evidence strongly supports considering HIPEC.

Combining data from three trials with 500 participants, researchers found that CRS + HIPEC + systemic chemotherapy probably decreases all-cause mortality compared to CRS + systemic chemotherapy alone. The hazard ratio was 0.73 (95% CI 0.57 to 0.93), which translates to 46.3% mortality in the HIPEC group versus 57.4% in the surgery-plus-chemotherapy-only group over 32-70 months of follow-up.

Regarding quality of life, one trial with 71 participants found little to no difference between groups (mean difference 4.85, 95% CI -7.74 to 17.44 on a 0-100 scale).

For serious adverse events:

• The proportion of people experiencing serious adverse events showed no significant difference (26.7% with HIPEC vs. 25.2% without; risk ratio 1.06, 95% CI 0.73 to 1.54)
• However, the number of serious adverse events per participant was higher with HIPEC (41.4 events per 100 participants vs. 32.6 events; rate ratio 1.27, 95% CI 1.09 to 1.49)

Time to disease progression also favored the HIPEC group with a hazard ratio of 0.73 (95% CI 0.60 to 0.89), meaning patients experienced longer periods before their cancer worsened.

Findings for Colorectal Cancer

For colorectal cancer peritoneal metastases, the results present a more complex picture that depends on what treatment HIPEC is being compared to.

When comparing CRS + HIPEC + systemic chemotherapy versus CRS + systemic chemotherapy (without HIPEC), one large trial with 265 participants found:

• No difference in all-cause mortality (hazard ratio 1.00, 95% CI 0.63 to 1.58; 60.6% mortality in both groups over 64 months)
• Increased serious adverse events with HIPEC (25.6% vs. 15.2%; risk ratio 1.69, 95% CI 1.03 to 2.77)
• No difference in time to disease progression (hazard ratio 0.91, 95% CI 0.72 to 1.16)

However, when comparing CRS + HIPEC + systemic chemotherapy versus systemic chemotherapy alone, one trial with 105 participants found:

• Probably decreased mortality with HIPEC (hazard ratio 0.55, 95% CI 0.32 to 0.95; 40.8% mortality with HIPEC vs. 60.8% with chemotherapy alone over 22 months)

What These Results Mean

The findings suggest different treatment recommendations depending on cancer type. For ovarian cancer patients with advanced disease undergoing interval cytoreductive surgery, CRS + HIPEC + systemic chemotherapy should probably be considered standard of care based on the survival benefit demonstrated across multiple trials.

For colorectal cancer, the addition of HIPEC to CRS + systemic chemotherapy doesn't appear to improve survival but increases complication risks. However, the combination of CRS + HIPEC + systemic chemotherapy does seem superior to systemic chemotherapy alone. This suggests that surgery remains important, but the value of adding HIPEC is questionable for most colorectal patients.

For gastric cancer, the evidence remains too uncertain to make any strong recommendations. The limited and conflicting data means patients should consider HIPEC only in the context of clinical trials where additional data can be gathered.

The researchers addressed controversies around the PRODIGE-7 trial (the main colorectal cancer study), explaining why they believe its findings should guide practice despite some expert criticisms. They emphasized that it was a high-quality trial with appropriate methodology.

Study Limitations

This review has several important limitations that patients should understand. Most comparisons included only one trial per cancer type (except ovarian cancer), which limits the strength of conclusions. The gastric cancer evidence was particularly sparse and uncertain.

Additionally, the studies used different chemotherapy drugs and protocols for HIPEC, including:

• Mitomycin C
• Oxaliplatin with 5-fluorouracil
• Cisplatin

This variation makes it difficult to determine if specific drugs or protocols might be more effective than others. The researchers could not perform planned subgroup analyses due to insufficient data.

Quality of life data was limited, only available for ovarian cancer, which is an important consideration for patients weighing treatment options and potential side effects.

Patient Recommendations

Based on this comprehensive review, patients should consider the following recommendations:

1. For ovarian cancer with peritoneal metastases: Discuss CRS + HIPEC + systemic chemotherapy with your care team, as it appears to provide survival benefits for advanced disease requiring interval cytoreductive surgery.
2. For colorectal cancer with peritoneal metastases: CRS + systemic chemotherapy should be standard care. HIPEC should only be considered in research settings focusing on specific patient subgroups or treatment protocols.
3. For gastric cancer with peritoneal metastases: The evidence remains too uncertain to recommend HIPEC outside of clinical trials where more data can be collected.
4. For all patients: Discuss both the potential benefits and risks of increased serious adverse events with HIPEC. Consider seeking care at high-volume centers with experience in these complex procedures, as complication rates are significantly lower at specialized centers.
5. Participate in shared decision-making with your oncology team, considering your individual situation, values, and preferences when choosing among treatment options.

Source Information

Original Article Title: 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

Authors: Kurinchi Gurusamy, Jeffrey Leung, Claire Vale, Danielle Roberts, Audrey Linden, Xiao Wei Tan, Priyal Taribagil, Sonam Patel, Elena Pizzo, Brian Davidson, Mark Saunders, Omer Aziz, Sarah T. O'Dwyer

Publication: World Journal of Surgery, 2024;48:1385–1403

DOI: 10.1002/wjs.12186

This patient-friendly article is based on peer-reviewed research funded by the National Institute for Health and Care Research (UK) and United Kingdom Research and Innovation Medical Research Council.