Adjuvant Systemic Chemotherapy vs Active Surveillance Following Up-front Resection of Isolated Synchronous Colorectal Peritoneal Metastases

Abstract

IMPORTANCE To date, there are no data on the value of adjuvant systemic chemotherapy following up-front resection of isolated synchronous colorectal peritoneal metastases.OBJECTIVE To assess the association between adjuvant systemic chemotherapy and overall survival following up-front resection of isolated synchronous colorectal peritoneal metastases. DESIGN, SETTING, AND PARTICIPANTSIn this population-based, observational cohort study using nationwide data from the Netherlands Cancer Registry (diagnoses between January 1, 2005, and December 31, 2017; follow-up until January 31, 2019), 393 patients with isolated synchronous colorectal peritoneal metastases who were alive 3 months after up-front complete cytoreductive surgery with hyperthermic intraperitoneal chemotherapy were included. Patients allocated to the adjuvant systemic chemotherapy group were matched (1:1) with those allocated to the active surveillance group by propensity scores based on patient-, tumor-, and treatment-level covariates.EXPOSURES Adjuvant systemic chemotherapy, defined as systemic chemotherapy without targeted therapy, starting within 3 months postoperatively. MAIN OUTCOMES AND MEASURESOverall survival was compared between matched groups using Cox proportional hazards regression analysis adjusted for residual imbalance. A landmark analysis was performed by excluding patients who died within 6 months postoperatively. A sensitivity analysis was performed to adjust for unmeasured confounding by major postoperative morbidity. RESULTSOf 393 patients (mean [SD] age, 61 [10] years; 181 [46%] men), 172 patients (44%) were allocated to the adjuvant systemic chemotherapy group. After propensity score matching of 142 patients in the adjuvant systemic chemotherapy group with 142 patients in the active surveillance group, adjuvant systemic chemotherapy was associated with improved overall survival compared with active surveillance (median, 39.2 [interquartile range, 21.1-111.1] months vs 24.8 [interquartile range, 15.0-58.4] months; adjusted hazard ratio [aHR], 0.66; 95% CI, 0.49-0.88; P = .006), which remained consistent after excluding patients who died within 6 months postoperatively (aHR, 0.68; 95% CI, 0.50-0.93; P = .02) and after adjustment for major postoperative morbidity (aHR, 0.71; 95% CI, 0.53-0.95). CONCLUSIONS AND RELEVANCEFindings of this study suggest that in patients undergoing up-front resection of isolated synchronous colorectal peritoneal metastases, adjuvant systemic chemotherapy appeared to be associated with improved overall survival. Although randomized trials are needed to address the influence of potential residual confounding and allocation bias on this association, results of this study may be used for clinical decision-making in this patient group for whom no data are available.

The Impact of Neoadjuvant Chemotherapy on the Surgical Management of Colorectal Peritoneal Metastases: A Systematic Review and Meta-Analysis

“…A population-based cohort study of almost 400 patients from the Netherlands showed survival benefit in adjuvant chemotherapy (39 months median OS) versus active surveillance (25 months median OS) in patients receiving upfront CRS and HIPEC. 30 Similarly from Sweden, a recent retrospective study of 131 consecutive patients reported a median OS of 40 months after complete cytoreduction, with 60% of the study population receiving adjuvant chemotherapy. 31 The authors question the need for NAC due to the favourable reported survival.…”

Perioperative chemotherapy in colorectal cancer with peritoneal metastases: a global propensity score matched study

“…Looking at the literature, there are no randomised trials and only one well-designed propensity-score matched study to lean on for the evaluation of adjuvant systemic treatment. 8 However, this study had a very narrow inclusion of patients with only synchronous CRCPM. It could conclude that adjuvant chemotherapy was superior to active surveillance.…”

“… 4 , 5 There are several larger case series that have in multivariable analyses shown that adjuvant therapy may have a positive effect and one propensity score matched study. 6 , 7 , 8 On the other hand, several studies have not shown the same positive outcome for adjuvant therapy 7 , 9 , 10 . The use of neoadjuvant therapy is even more controversial.…”

Lymph Node Metastases from Visceral Peritoneal Colorectal Metastases are Associated with Systemic Recurrence

“…As such, the prediction of failure patterns after CRS?HIPEC may aid in the triage of patients to adjuvant treatment (i.e., after HIPEC). Although the benefit of adjuvant treatment after HIPEC is not well established, [29][30][31] it is possible that patients with LNM-VPCM comprise a subgroup for which this treatment may prove beneficial. It should be noted that lymphatic metastases are well accepted as an indication for adjuvant treatment in primary CRC.…”