Title

The efficacy of second-look surgery with hyperthermic intraperitoneal chemotherapy and cytoreductive surgery in adult patients with advanced stage colorectal carcinoma

Date of Award

Spring 2020

Degree Name

Master of Medical Science (Physician Assistant)

Department

Physician Assistant; College of Health Sciences

First Advisor

Lisa Murphy

Second Advisor

Amanda Seymour

Abstract

Introduction: In 2020, it is estimated that there will be approximately 104,000 new cases of colon cancer. Peritoneal carcinoma (PC) represents the second most frequent recurrence of primary colorectal cancer. The mainstay of treatment for patients with advanced stage colorectal cancer at risk of developing PC after initial intervention is surveillance. However, PC is not detectable by imaging, symptoms, or tumor markers with current techniques and technology. Therefore, this review analyzes how to identify the patient population at a high risk for developing PC and performing a mandatory second-look surgery (SLS), typically a laparotomy, with hyperthermic intraperitoneal chemotherapy (HIPEC) or prophylactic HIPEC at the time of initial intervention compared to the standard of care.

Methods: A literature search was conducted through PubMed and Google Scholar in November 2018. A total of eleven articles were selected based on the following exclusion criteria: 1. Studies involving meta-analysis 2. Studies involving animals 3. Studies involving carcinomas other than advanced, primary colorectal carcinomas with the risk of PC 4. Studies involving adolescents. A final six articles were then analyzed and compared.

Results: The evidence collected by each of the studies demonstrated a statistically significant reduction in the mortality rate in patients with advanced stage colorectal cancer at risk of developing PC. However, the evidence collected was not strong enough to confirm what patient population is at most risk of developing PC and who would benefit the most from mandatory second-look surgery. Three studies compared the use of second-look surgery after treatment of colorectal cancer. All three studies support the promising results of second-look surgery but acknowledge the need for conducting randomized trial to further support and validate the data. Two of the studies compared the effectiveness of cytoreductive surgery and intraperitoneal chemotherapy vs the standard of care (systemic chemotherapy and surveillance) to treat PC of colorectal origin. Both studies showed the overall benefit of cytoreductive surgery and intraperitoneal chemotherapy. However, only one showed statistically significant disease-free survival due to the early termination of the other study. The final study recognized potential risk factors for developing PC to identify the correct population of patients that should be considered for second-look surgery with HIPEC and CRS.

Discussion: Significant positive results were found in most of the articles, but outcome measures varied among the studies. Limited sample populations, design of the studies, adequate follow-up and biases prevent the findings from having statistical power and therefore clinical significance. Consequently, performing second-look surgery with HIPEC and CRS in patients with colorectal cancer at high risk of developing PC cannot be confirmed despite many positive and promising findings. Further studies, including randomized trials, should be encouraged to decrease the mortality rate in a select group of patients with colorectal cancer at high risk of developing PC.

Conclusion: In adult patients with advanced, primary colorectal cancer who are at a high risk of developing PC, second-look surgery with HIPEC and CRS should be considered over the standard of care (systemic chemotherapy and surveillance) to improve patient outcomes and reduce mortality rates. Identifying the patient population at most risk for developing PC of colorectal origin is essential to achieve the greatest benefit of second-look surgery with HIPEC and CRS. Second-look surgery is not without risks and the morbidity and mortality of the procedure should be further studied. Future studies should focus on identifying the patient population most at risk in addition to the long-term outcomes of second-look surgery with HIPEC and CRS.

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The efficacy of second-look surgery with hyperthermic intraperitoneal chemotherapy and cytoreductive surgery in adult patients with advanced stage colorectal carcinoma

Introduction: In 2020, it is estimated that there will be approximately 104,000 new cases of colon cancer. Peritoneal carcinoma (PC) represents the second most frequent recurrence of primary colorectal cancer. The mainstay of treatment for patients with advanced stage colorectal cancer at risk of developing PC after initial intervention is surveillance. However, PC is not detectable by imaging, symptoms, or tumor markers with current techniques and technology. Therefore, this review analyzes how to identify the patient population at a high risk for developing PC and performing a mandatory second-look surgery (SLS), typically a laparotomy, with hyperthermic intraperitoneal chemotherapy (HIPEC) or prophylactic HIPEC at the time of initial intervention compared to the standard of care.

Methods: A literature search was conducted through PubMed and Google Scholar in November 2018. A total of eleven articles were selected based on the following exclusion criteria: 1. Studies involving meta-analysis 2. Studies involving animals 3. Studies involving carcinomas other than advanced, primary colorectal carcinomas with the risk of PC 4. Studies involving adolescents. A final six articles were then analyzed and compared.

Results: The evidence collected by each of the studies demonstrated a statistically significant reduction in the mortality rate in patients with advanced stage colorectal cancer at risk of developing PC. However, the evidence collected was not strong enough to confirm what patient population is at most risk of developing PC and who would benefit the most from mandatory second-look surgery. Three studies compared the use of second-look surgery after treatment of colorectal cancer. All three studies support the promising results of second-look surgery but acknowledge the need for conducting randomized trial to further support and validate the data. Two of the studies compared the effectiveness of cytoreductive surgery and intraperitoneal chemotherapy vs the standard of care (systemic chemotherapy and surveillance) to treat PC of colorectal origin. Both studies showed the overall benefit of cytoreductive surgery and intraperitoneal chemotherapy. However, only one showed statistically significant disease-free survival due to the early termination of the other study. The final study recognized potential risk factors for developing PC to identify the correct population of patients that should be considered for second-look surgery with HIPEC and CRS.

Discussion: Significant positive results were found in most of the articles, but outcome measures varied among the studies. Limited sample populations, design of the studies, adequate follow-up and biases prevent the findings from having statistical power and therefore clinical significance. Consequently, performing second-look surgery with HIPEC and CRS in patients with colorectal cancer at high risk of developing PC cannot be confirmed despite many positive and promising findings. Further studies, including randomized trials, should be encouraged to decrease the mortality rate in a select group of patients with colorectal cancer at high risk of developing PC.

Conclusion: In adult patients with advanced, primary colorectal cancer who are at a high risk of developing PC, second-look surgery with HIPEC and CRS should be considered over the standard of care (systemic chemotherapy and surveillance) to improve patient outcomes and reduce mortality rates. Identifying the patient population at most risk for developing PC of colorectal origin is essential to achieve the greatest benefit of second-look surgery with HIPEC and CRS. Second-look surgery is not without risks and the morbidity and mortality of the procedure should be further studied. Future studies should focus on identifying the patient population most at risk in addition to the long-term outcomes of second-look surgery with HIPEC and CRS.