In this study, we have constructed a nomogram and validated it with satisfied performances in a validation cohort of PM patients. This nomogram can individually predict 0.5-,1-,2- and 3-year OS of PM patients. As the prognosis of synchronous peritoneal metastasis of colorectal cancer is extremely poor, and the median survival time of its natural outcome is about 0.5 years. The 3-year survival rate is very low after CRS plus HIPEC treatment. Therefore, we have adopted multiple survival time within three years, which is more precise and more suitable in clinical practice. By incorporating demographic and clinical characteristics, the nomogram showed good discrimination and calibration performance by C-index and calibration curve, and is an easy-to-use noninvasive tool for clinicians to estimate the OS and personalize subsequent treatments for individuals. More efficient chemotherapy regime is needed for PM patients with low probability of survival.
PM often is considered to be the terminal state, and obtains worst survival, comparing to other organ metastases. However, the median survival of CRS plus systemic chemotherapy can reach 16 months, which was consistent with the survival of 15.6 months in this study. PCI, CRS and CA19-9 are related to the prognosis of PM patients both in our study and previous studies 23–25. CA19-9 is one important predictor of disease recurrence and associated with postoperative peritoneal recurrence26. In our nomogram, PCI score and CRS act the important roles in the model, especially PCI score. PCI score can be obtained by radiological examination and surgical evaluation. The sensitivity of CT scan in diagnosis of PM nodules < 5 mm is only 11–48%. The limited sensitivity of CT scans can influence the diagnosis of PM, the diagnostic power of PM can be improved with the development of artificial intelligence to assist the imaging diagnosis27. Therefore, radiological PCI is less sensitive than surgical PCI28–29. In PM with PCI score > 17, CRS + HIPEC does not offer additional survival benefit30. CRS can resolute bowel obstruction and remit bleeding to improve quality of life and create good physical condition to receive systematic chemotherapy and prolong the OS as possible31–32. The survival benefit can exceed the disadvantage of high risks of surgical complications for CRS.
It is generally believed that the prognosis of multiple organ metastasis will be worse than single organ metastasis. However, one study suggested that colorectal cancer with liver/lung metastasis obtained similar survival to those with peritoneal-only involvement33. We thought the survival of synchronous peritoneal metastasis is extremely poor than multiple organ metastasis including liver/lung metastasis, which can survive for more than 2 years in many patients. Therefore, the presence of liver/lung metastasis may not be a separate factor affecting the prognosis for synchronous peritoneal metastasis of colorectal cancer patients.
Sugarbaker firstly proposed CRS procedure in PM and reported the median operation time was 8 h (5–10 h) with 3.9L (0.5-30L) of blood loss during operation. The overall morbidity rate varied from 23 to 44%, and the mortality rate ranged from 0 to 12% in nine different institutions34. The delayed complications that may result from extensive CRS included both anatomic (bowel obstruction, perforation, and hemorrhage) and functional symptoms (short bowel syndrome, and uncontrolled diarrhea). The PRODIGE 7 study which compares CRS with or without HIPEC in PM shows that the incidence of surgical complications above grade 3 was 13.6%-24.1%35. Therefore, CRS was not suitable for every patient, and even fewer patients have achieved CC 0–1. In this study, only 68 patients (20.4%) obtain the opportunity to receive CRS and achieve CC 0–1.
Several prognostic scores have been developed to predict the OS of PM patients in CRC. PSDSS and COMPASS are the most commonly applied12, 36. However, overall survival was analyzed according to five tiers of estimated disease severity in PSDSS. The calculation of the PSDSS is not based on the regression coefficient of a Cox proportional hazard model, it cannot predict the individualized survival rate of patients. The COMPASS included age, regional lymph node status, PCI and pathological features. It can guide clinicians to predict the OS after operating CRS plus HIPEC in different stages of PM. In addition, a study shown that the prediction effect of COMPASS is better than that of the PSDSS model37. The C-index of the training cohort of the COMPASS model was 0.72( 95%CI, 0.66–0.78)12, which was similar to the model in our study(0.713, 95%CI 0.674–0.752). When we took the training cohort of our model to be an external validation cohort of the COMPASS. The C-index of the external validation cohort was 0.681(95% CI, 0.64–0.72), that the result indicated a comparable database between the two cohorts. Both PSDSS and COMPASS cannot predict the prognosis of patients who do not have the opportunity to surgery. The variables in the nomogram of this study can be easily obtained at the initial diagnosis in clinic for patient selection. It is also applicable to some patients who have not been able to obtain pathological tissue types and lymph node infiltration results. We believe that this model is an innovative and practical tool for clinicians to provide patients with predicted individualized survival and guide the surveillance.
There are some limitations in this study. Firstly, this study was a retrospective analysis, potential selection and recall bias may exist. Secondly, the PCI in this model are obtained during surgery and was classified at 16, detailed PCI scores are needed for each patient in future study to establish better association with survival. Lastly, the sample size of PM patients in the nomogram is limited and only Asian population are included. Larger sample size and population from other areas are needed in future work. The accuracy of this nomogram model could be further improved.