A total neoadjuvant chemotherapy approach is associated with improved recurrence‐free survival in patients with colorectal peritoneal metastases undergoing cytoreductive surgery and HIPEC

Abstract

Background The primary aim of this study is to evaluate the oncologic outcomes of two popular systemic chemotherapy approaches in patients with colorectal peritoneal metastases (CPM) undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS‐HIPEC). Methods We performed a dual‐center retrospective review of consecutive patients who underwent CRS‐HIPEC for CPM due to high or intermediate‐grade colorectal cancer. Patients in the total neoadjuvant therapy (TNT) group received 6 months of preoperative chemotherapy. Patients in the “sandwich” (SAND) chemotherapy group received 3 months of preoperative chemotherapy with a maximum of 3 months of postoperative chemotherapy. Results A total of 34 (43%) patients were included in the TNT group and 45 (57%) patients in the SAND group. The median overall survival (OS) in the TNT and SAND groups were 77 and 61 months, respectively (p = 0.8). Patients in the TNT group had significantly longer recurrence‐free survival (RFS) than the SAND group (29 vs. 12 months, p = 0.02). In a multivariable analysis, the TNT approach was independently associated with improved RFS. Conclusion In this retrospective study, a TNT approach was associated with improved RFS, but not OS when compared with a SAND approach. Further prospective studies are needed to examine these systemic chemotherapeutic approaches in patients with CPM undergoing CRS‐HIPEC.

Consensus Guideline for the Management of Colorectal Cancer with Peritoneal Metastases

“…Three studies (<200 patients each) suggested a survival advantage of neoadjuvant therapy followed by CRS compared to upfront CRS [45, 46, 55]. Studies from the Peritoneal Surface Oncology Group International (PSOGI) Global Registry, with a sample size of over 2,000 patients, the United States HIPEC (Hyperthermic Intraperitoneal Chemotherapy) Collaborative, and several single institution studies failed to demonstrate a benefit of neoadjuvant therapy [43, 44, 47–54]. Proponents of neoadjuvant therapy argue for its potential to reduce PCI and increase complete cytoreduction rates, although this was not uniformly demonstrated across studies [55].…”

“…Of 72 clinical trials for metastatic CRC from 2003-2016, only seven trials reported inclusion of patients with PM [7]. Our systematic review (Table 4, Supplementary Table 1) synthesized findings from 13 observational studies, which reported receipt of systemic therapy for patients undergoing CRS for CRC-PM, with no published randomized controlled trials (RCTs) to date [43][44][45][46][47][48][49][50][51][52][53][54][55]. The timing, duration, and the agents used for neoadjuvant chemotherapy varied across studies.…”

“…As highlighted in our systematic review (Table 4, Supplementary Table 1), evidence regarding adjuvant systemic chemotherapy following complete CRS for CRC-PM remains equivocal [43][44][45][46][47][48][49][50][51][52][53][54][55]. Its role is better established in patients undergoing upfront CRS without neoadjuvant therapy (Block 3), but its role in a perioperative or "sandwich" regimen is more complex.…”

Systemic Chemotherapy in Colorectal Peritoneal Metastases Treated with Cytoreductive Surgery: Systematic Review and Meta-Analysis

“…These articles were extensively reviewed, and six were excluded due to a high rate of incomplete surgery, CC2 > 25% ( Table S1 ); finally, 15 studies (4523 patients) were included in the quantitative analysis ( Figure 1 ). Of these, 14 were case series (one prospective cohort study [ 21 ] and 13 were retrospective, of which 11 were cohort studies [ 5 , 9 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ] and two were case-control studies with propensity score analysis [ 31 , 32 ]) and one was a randomized controlled trial [ 13 ]. Four studies were monocentric, and 11 were multicentric; the median year of patient enrollment was 2009 (IQR range 2007–2012).…”

Neoadjuvant chemotherapy does not improve survival for patients with high volume colorectal peritoneal metastases undergoing cytoreductive surgery

“…Neoadjuvant chemotherapy for CRPM has been demonstrated to be a safe and feasible option, however there is conflicting evidence to support its efficacy. Confounding factors of heterogenous patient selection, small cohort studies, diversity in chemotherapy regimens, and most significantly the focus on low volume CRPM complicate the establishment of high-quality recommendations or their generalisability to patients with relatively advanced peritoneal disease [ 13 , 23 – 25 ]. The primary aim of this study was to evaluate whether neoadjuvant chemotherapy improves survival in patients with high volume CRPM undergoing CRS.…”