Research Article| Volume 49, ISSUE 3, P604-610, March 2023

External validation of COMPASS and BIOSCOPE prognostic scores in colorectal peritoneal metastases treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC)

Published:October 21, 2022DOI:



      The selection of patients undergoing cytoreductive- surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is crucial. BIOSCOPE and COMPASS are prognostic scores designed to stratify survival into four classes according to clinical and pathological features. The purpose of this study is to analyze the prognostic role of these scores using a large cohort of patients as an external reference.


      Overall survival analysis was performed using Log-Rank and Kaplan-Meier curves for each score. The probability of survival at 12, 36, and 60 months was tested using receiver operating characteristic (ROC) curves to determine sensitivity and specificity.


      From the validation cohort of 437 patients, the analysis included 410 patients in the COMPASS group and 364 patients in the BIOSCOPE group (100% data completeness). We observed a different patient distribution between classes (high-risk for BIOSCOPE compared to COMPASS, p = 0.0001). Nevertheless, both COMPASS and BIOSCOPE effectively stratified overall survival (Log-Rank, p = 0.0001 in both cases), with a lack of discrimination between COMPASS classes II and III (p = n.s.). COMPASS at 12 m and BIOSCOPE at 60 m showed the best performance in terms of survival prediction (AUC of 0.82 and 0.81). The specificity of the two tests is good (median 81.3%), whereas sensibility is quite low (median 64.2%).


      Following external validation in a large population of patients with CRC-PM who are eligible for surgery, the COMPASS and BIOSCOPE scores exhibit high inter-test variability but effectively stratify cancer-related mortality risk. While the quality of the scores is similar, BIOSCOPE shows better inter-tier differentiation, suggesting that tumor molecular classification could improve test discrimination capability. More powerful stratification scores with the inclusion of novel predictors are needed.


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        • Ferlay J.
        • Colombet M.
        • Soerjomataram I.
        • Mathers C.
        • Parkin D.M.
        • Piñeros M.
        • et al.
        Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods.
        Int J Cancer. 2019; 144: 1941-1953
        • Quere P.
        • Facy O.
        • Manfredi S.
        • Jooste V.
        • Faivre J.
        • Lepage C.
        • et al.
        Epidemiology, management, and survival of peritoneal carcinomatosis from colorectal cancer: a population-based study.
        Dis Colon Rectum. 2015; 58: 743-752
        • Jayne D.G.
        • Fook S.
        • Loi C.
        • Seow-Choen F.
        Peritoneal carcinomatosis from colorectal cancer.
        Br J Surg. 2002; 89: 1545-1550
        • Franko J.
        • Shi Q.
        • Meyers J.P.
        • Maughan T.S.
        • Adams R.A.
        • Seymour M.T.
        • et al.
        Prognosis of patients with peritoneal metastatic colorectal cancer given systemic therapy: an analysis of individual patient data from prospective randomised trials from the Analysis and Research in Cancers of the Digestive System (ARCAD) database.
        Lancet Oncol. 2016; 17: 1709-1719
        • Verwaal V.J.
        • Van Tinteren H.
        • Van Ruth S.
        • Fan Zoetmulder
        Predicting the survival of patients with peritoneal carcinomatosis of colorectal origin treated by aggressive cytoreduction and hyperthermic intraperitoneal chemotherapy.
        Br J Surg. 2004; 91: 739-746
        • Elias D.
        • Lefevre J.H.
        • Chevalier J.
        • Brouquet A.
        • Marchal F.
        • Classe J.M.
        • et al.
        Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin.
        J Clin Oncol. 2009; 27: 681-685
        • Quénet F.
        • Elias D.
        • Roca L.
        • Goéré D.
        • Ghouti L.
        • Pocard M.
        • et al.
        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: 256-266
        • 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: 585-594
        • Simkens G.A.
        • Wintjens A.G.W.E.
        • Rovers K.P.
        • Nienhuijs S.W.
        • de Hingh I.H.
        Effective strategies to predict survival of colorectal peritoneal metastases patients eligible for cytoreductive surgery and HIPEC.
        Cancer Manag Res. 2021; 13: 5239-5249
        • Gillern S.M.
        • Chua T.C.
        • Stojadinovic A.
        • Esquivel J.
        KRAS status in patients with colorectal cancer peritoneal carcinomatosis and its impact on outcome.
        Am J Clin Oncol. 2010; 33: 456-460
        • Chua T.C.
        • Morris D.L.
        • Esquivel J.
        Impact of the peritoneal surface disease severity score on survival in patients with colorectal cancer peritoneal carcinomatosis undergoing complete cytoreduction and hyperthermic intraperitoneal chemotherapy.
        Ann Surg Oncol. 2010; 17: 1330-1336
        • Simkens G.A.
        • van Oudheusden T.R.
        • Nieboer D.
        • Steyerberg E.W.
        • Rutten H.J.
        • Luyer M.D.
        • et al.
        Development of a prognostic nomogram for patients with peritoneally metastasized colorectal cancer treated with cytoreductive surgery and HIPEC.
        Ann Surg Oncol. 2016; 23: 4214-4221
        • Schneider M.A.
        • Eden J.
        • Pache B.
        • Laminger F.
        • Lopez-Lopez V.
        • Steffen T.
        • et al.
        Mutations of RAS/RAF proto-oncogenes impair survival after cytoreductive surgery and HIPEC for peritoneal metastasis of colorectal origin.
        Ann Surg. 2018; 268: 845-853
        • Tonello M.
        • Baratti D.
        • Sammartino P.
        • Di Giorgio A.
        • Robella M.
        • Sassaroli C.
        • et al.
        Microsatellite and RAS/RAF mutational status as prognostic factors in colorectal peritoneal metastases treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC).
        Ann Surg Oncol. 2021;
        • Cashin P.H.
        • Graf W.
        • Nygren P.
        • Mahteme H.
        Patient selection for cytoreductive surgery in colorectal peritoneal carcinomatosis using serum tumor markers: an observational cohort study.
        Ann Surg. 2012; 256: 1078-1083
        • Cashin P.H.
        • Graf W.
        • Nygren P.
        • Mahteme H.
        Comparison of prognostic scores for patients with colorectal cancer peritoneal metastases treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
        Ann Surg Oncol. 2013; 20: 4183-4189
        • Esquivel J.
        • Lowy A.M.
        • Markman M.
        • Chua T.
        • Pelz J.
        • Baratti D.
        • et al.
        The American society of peritoneal surface malignancies (ASPSM) multiinstitution evaluation of the peritoneal surface disease severity score (PSDSS) in 1,013 patients with colorectal cancer with peritoneal carcinomatosis.
        Ann Surg Oncol. 2014; 21: 4195-4201
        • De Roock W.
        • De Vriendt V.
        • Normanno N.
        • Ciardiello F.
        • Tejpar S.
        KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer.
        Lancet Oncol. 2011; 12: 594-603
        • Allegra C.J.
        • Rumble R.B.
        • Hamilton S.R.
        • Mangu P.B.
        • Roach N.
        • Hantel A.
        • et al.
        Extended RAS gene mutation testing in metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy: American society of clinical Oncology provisional clinical opinion update 2015.
        J Clin Oncol. 2016; 34: 179-185
        • Van Cutsem E.
        • Köhne C.H.
        • Láng I.
        • Folprecht G.
        • Nowacki M.P.
        • Cascinu S.
        • et al.
        Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status.
        J Clin Oncol. 2011; 29 (–9): 2011
        • Italiano A.
        • Hostein I.
        • Soubeyran I.
        • Fabas T.
        • Benchimol D.
        • Evrard S.
        • et al.
        KRAS and BRAF mutational status in primary colorectal tumors and related metastatic sites: biological and clinical implications.
        Ann Surg Oncol. 2010; 17: 1429-1434
        • Arjona-Sanchez A.
        • Rodriguez-Ortiz L.
        • Baratti D.
        • Schneider M.A.
        • Gutiérrez-Calvo A.
        • García-Fadrique A.
        • et al.
        RAS mutation decreases overall survival after optimal cytoreductive surgery and hyperthermic intraperitoneal chemotherapy of colorectal peritoneal metastasis: a modification proposal of the peritoneal surface disease severity score.
        Ann Surg Oncol. 2019; 26: 2595-2604
        • Abboud K.
        • André T.
        • Brunel M.
        • Ducreux M.
        • Eveno C.
        • Glehen O.
        • et al.
        Management of colorectal peritoneal metastases: expert opinion.
        J Vis Surg. 2019; 156
        • Rovers K.P.
        • Simkens G.A.
        • Punt C.J.
        • et al.
        Perioperative systemic therapy for resectable colorectal peritoneal metastases: sufficient evidence for its widespread use? A critical systematic review.
        Crit Rev Oncol Hematol. 2017; 114: 53-62
        • Waite K.
        • Youssef H.
        The role of neoadjuvant and adjuvant systemic chemotherapy with cytoreductive surgery and heated intraperitoneal chemotherapy for colorectal peritoneal metastases: a systematic review.
        Ann Surg Oncol. 2017; 24: 705-720
        • Devilee R.A.
        • Simkens G.A.
        • Van Oudheusden T.R.
        • Rutten H.J.
        • Creemers G.
        • Tije A.J.T.
        • et al.
        Increased survival of patients with synchronous colorectal peritoneal metastases receiving preoperative chemotherapy before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
        Ann Surg Oncol. 2016; 23: 2841-2848
        • Ceelen W.
        • Van Nieuwenhove Y.
        • Putte D.V.
        • Pattyn P.
        Neoadjuvant chemotherapy with bevacizumab may improve outcome after cytoreduction and hyperthermic intraperitoneal chemoperfusion (HIPEC) for colorectal carcinomatosis.
        Ann Surg Oncol. 2014; 21 (PCI minore in NAC: Devilee (p 0.02), rovers trial, beal): 3023-3028
        • Beal E.W.
        • Suarez-Kelly L.P.
        • Kimbrough C.W.
        • Johnston F.M.
        • Greer J.
        • Abbott D.E.
        • et al.
        Impact of neoadjuvant chemotherapy on the outcomes of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: a multi-institutional retrospective review.
        J Clin Med. 2020 Mar 10; 9 (PMID: 32164300; PMCID: PMC7141272): 748
        • Rovers K.
        • Bakkers C.
        • Simkens G.
        • A.Burger J.W.
        • Nienhuijs S.W.
        • Creemers G.-J.M.
        • et al.
        Perioperative systemic therapy and cytoreductive surgery with HIPEC versus upfront cytoreductive surgery with HIPEC alone for isolated resectable colorectal peritoneal metastases: protocol of a multicentre, open-label, parallel-group, phase II-III, randomised, superiority study (CAIRO6).
        BMC Cancer. 2019; 19: 390
        • Schirripa M.
        • Nappo F.
        • Cremolini C.
        • Salvatore L.
        • Rossini D.
        • Bensi M.
        • et al.
        KRAS G12C metastatic colorectal cancer: specific features of a new emerging target population.
        Clin Colorectal Cancer. 2020; 19: 219-225