PMP is a rare disease, which tends to be an incidental finding either on imaging or during exploratory surgery performed for other indications. Present study demonstrated several independent factors for predicting survival of PMP patients, including sex, D-Dimer, CA125, CA19-9, PCI, and degree of radical surgery. Subsequently, we established a nomogram prediction model based on the identified significant prognostic factors, afterwards, the model was subjected to bootstrap internal validation by calibration curve and C-index.
Among the three routinely used tumor markers in PMP[14], CA19-9 seems to be optimal independent prognosticators for PMP, which not only could predict survival but also recurrence, a lot of researches confirmed this conclusion[15-18], present study result was entirely consistent with the previous studies, CA19-9 possess highest prediction coefficient and was the best prediction index in our predition model. CA125 can predict ovarian cancer in general practice[19], which is also expressed in peritoneal malignancy, and can be elevated in patients with any source of peritoneal irritation.[1] In present study, CA125 seems also to be a usefull marker for prediction survival of PMP, a high CA125 level denotes a poor prognosis for PMP. Although univariate analysis revealed elevated CEA level was associated with worse survival in PMP, nevertheless, multivariate analysis did not reach a significant statistics, former study also confirmed CEA owns low value in prediction survival of PMP[15].
Present study also evaluated the predicting value of new tumor markers (CA724 and CA242) in PMP patients, univariate analysis all showed elevated levels of the two markers were all associated poor survival for PMP, while in multivariate analysis, all the two did not show significant prognostic value, due to extremely low incidence rate of PMP, fewer cases were included in present study, therefore, researches with larger sample size and longer follow-up time are needed to assess the predictive value of CA724 and CA242 for PMP.
Gender is considered an important factor for patient’s oncologic outcome[20]. A meta-analysis showed that there was an influence of gender on OS in colorectal cancer patients, females had significantly better OS than males. [21] Also, there was a better OS in women compared to men in bladder and kidney cancer patients. [20] This study found that males with PMP had a poor survival than females, which is consistent with previous research reports[2, 7], women tend to present at an earlier stage than men for secondary to the rapidly enlarging ovarian masses, which become symptomatic or are obvious clinically[1], so women can get more timely treatment. These results suggest that gender seems to be a significant factor influencing survival results among PMP patients.
Elevated pretreatment D-Dimer level has been confirmed markedly correlated with TNM staging[22] and associated with poor OS in patients with solid tumors [23], for instance, colorectal cancer[22], pancreatic carcinoma[24], lung cancer[25, 26], and so on. Interestingly, we discovered a high D-Dimer level was also associated with a poor survival prognosis in PMP, to our knowledge, this was the first study to evaluate the prediction value of D-Dimer in PMP, in the future clinical practice, clinicians should pay more attention to the D-Dimer level of in PMP patients, the analysis of preoperative D-Dimer can be useful in predicting postoperative survival rate for PMP.
Tumor burden is a prognostic factor in predicting OS for cancer patients. The extent of disease in PMP is assessed by the PCI, a PCI≥20 always representing unresectable disease.[27] Former studies confirmed that PCI was the risk factors for postoperative morbidity in univariate analysis, however, no statistical significant correlation was found during the multivariate analysis[28], however, in present study, we found a higher PCI denotes a poor prognosis in PMP, it is easy to understand, a high tumor load often means a poor prognosis, this difference may be due to the small number of cases (n=53) and different variables included in the previous study. Completeness of cytoreduction is one of the most important prognostic factors for PMP[1], present study revealed that the MTD subgroup had a obvious poor survival than the CCRS group, this result was similar to the previous studies[29, 30], differently, a large proportion of participants in the former study can reach CCRS, while in our study, the majority of patient can only undergone major debulking surgery, we speculate that most PMP patients in China could not get correct PMP diagnosis timely and receive standard treatment. To summarise, a higher PCI and MTD indicates a poor survival for PMP, and vice versa.
A part of researchers reckon that the prognosis of PMP correlates closely to histopathological classification[31], oppositely, different opinions suggest that PMP is unlike other tumors, histopathology does not reliably predict tumor behaviour[32]. Present study revealed a high grade histopathology denotes a poor survival for PMP in univariate analysis, while in multivariate analysis, there was no correlation between histopathological grade and OS rate, so we speculate that predictive value of histopathological grade for PMP is relatively small. Similarly, although Barthel Index Score and albumin seemed to associated with prognosis of PMP in univariate analysis, which was similar to the former study[33, 34], the multivariate analysis did not reach significant difference, Barthel Index Score reflect the ability to perform the activities of daily life[35] and albumin reflect nutrition condition, which suggest that those effects on the prognosis of PMP patients is limited, but this conclusion needs to be confirmed by a large number of studies.
The present study established prognostic model for OS in PMP, the discrimination ability of OS in PMP was 0.880, so we think this is a valuable prediction model for PMP, which could provide more help for the prognosis judgment and treatment intervention of PMP patients, however, more studies are needed to confirm the conclusion, in particular with prospective large sample studies.
There were several limitations of present study. Firstly, due to the limitation of retrospective study, some data have not been followed up. Secondly, because the survival time of PMP patients is significantly longer than before, the proportion of end-point events is relatively small, it may lead to the instability of statistical conclusions, therefore, a longer follow-up is needed to confirm the conclusions in the future. Thirdly, the predictive accuracy and discriminative ability of established prognositic model in present study only undergone internal validation, a external validation with a separate cohort will be realized in the future. Finally, although the prediction model is relatively good for PMP, we think that there is still some other factors not included into the prediction model, such as KRAS mutations, which had been proved independently prognostic for progress free survival (PFS) in PMP patients, we speculate that KRAS mutations may also be independent prognostic factors for OS in PMP, future work will further verify this hypothesis.