| Part One:Different oncological outcomes of the same pathologic stage between patients with or without neoadjuvant chemoradiotherapy in rectal cancer:A propensity score-matched studyBackground:The same category definitions of the AJCC TNM staging system have been employed for both rectal cancer patients with and without neoadjuvant chemoradiotherapy(NCRT).However,NCRT could induce the therapeutic response of rectal cancer and different degrees of treatment response,and NCRT significantly improved the local recurrence of locally advanced rectal cancer,which put forward higher requirements for the prognosis evaluation of rectal cancer patients predicted by the 8th edition of TNM staging system.At present,there has not been a good study to analyze whether ypTNM staging system and pTNM staging system could predict prognosis equally accurately.Therefore,this study aimed to investigate whether there was a difference in the prognostic stratification between rectal cancer patients treated with NCRT and without NCRT using the same TNM pathological staging,and to verify whether the same TNM pathological staging was accurate between patients with NCRT or without NCRT.Methods:Between January 2008 and December 2015,2266 patients with rectal cancer were included in a retrospective observational study.Of these,413 patients received NCRT combined with total mesorectal resection(ypTNM group)and 1853 patients did not receive NCRT and were initially treated with surgery(pTNM group).The clinicopathological data of the enrolled patients were retrospectively analyzed and propensity score matching analysis method was adopted.The matching factors included clinicopathological factors such as sex,age,pathological TNM,T stage,N stage,distance from the anal edge and treatment time.After propensity score matching,comparisons of outcomes were performed using Kaplan-Meier analyses and log-rank test between the ypTNM and the matched pTNM.Results:After propensity score matching,there were not significant differences in sex,age,distance from the anal edge,treatment time,pathological TNM,T stage,N stage and other basic clinicopathological characteristics between the pTNM group and the ypTNM group(p<0.01).After propensity score matching,337 patients in the ypTNM group and 634 patients in the matched pTNM group were generated for analysis.Compared to stage ? and ? in the pTNM group,the 5-year DFS(90.91%vs.91.25%,p=0.83;84.58%vs.83.19%,p=0.34)and 5-year OS(98.48%vs.97.50%,p=0.76;92.95%vs.91.60%,p=0.98)of stage ? and ? in the matched ypTNM group were not significantly different.The 5-year LRFS of stage ?,? and ? were not different between the pTNM group and the matched ypTNM group(94.70%vs.97.50%,p=0.33;92.95%vs.95.80%,p=0.64;88.04%vs.86.23%,p=0.46).While the 5-year DFS,5-year DMFS and 5-year OS of stage ? in tthe pTNM group was significantly different from that in the matched ypTNM group(67.39%vs.52.90%,p=0.01;75.00%vs.61.59%,p=0.01;84.42%vs.75.36%,p=0.01).Conclusions:This study provided objective data by matching the clinicopathological characteristics of patients in the ypTNM group and the pTNM group with the propensity score,to compare whether patients in the two groups with the same pathological stage.It was clear that the current TNM staging system for rectal cancer patients with NCRT,as defined in rectal cancer patients without NCRT,was not an accurate assessment of LARC patients receiving NCRT,especially for long-term tumor outcomes in patients with ypTNM stage ? rectal cancer.But that the rationality of the ypTNM staging system performed for ypTNM ? and ypTNM ? patients with NCRT should be confirmed by further investigation.Part two:Conditional disease-free survival for rectal cancer patients with neoadjuvant chemoradiotherapyBackgroud:Clinicians usually use cumulative survival analysis to predict prognosis for rectal cancer patients with neoadjuvant chemoradiotherapy(NCRT)based on ypTNM.However,cumulative survival analysis does not reflect the dynamic changes in prognosis of rectal cancer patients with NCRT over time.Conditional survival analysis is a dynamic analysis method to predict the prognosis of patients based on their current survival status.The purpose of this study was to investigate the conditional disease-free survival(cDFS)in patients with different ypTNM stages of rectal cancer after NCRT,and to explore the application value of conditional survival analysis in prognosis prediction and follow-up monitoring strategy.Methods:Clinicopathologic data of 436 patients with rectal cancer having received NCRT and radical operation in Cancer Hospital between January 2004 and December 2016 were retrospectively reviewed.With reference to conditional probability,the 3-year cDFS of patients at different ypTNM stage was estimated using the Kaplan-Meier method.Conditional survival was calculated as cDFS(3|x),which is the probability of surviving for additional 3 years,given that the person has already survived x years.The formula is cDFS(3|x)=DFS(x+3)/DFS(x).Standard difference(d)was used to evaluate the differences in cDFS among patients with different ypTNM stages based on formula d=(P2-P1)/(P(1-P))1/2.Results:A total of 436 continuous patients were included.During the follow-up,108 patients(24.78%)developed local recurrence and distant metastasis.The 3-year accumulated DFS of patients with ypTNM stage 0,ypTNM stage ?,ypTNM stage ?,and ypTNM stage ? were 97.01%,93.10%,85.19%,and 64.19%,respectively.On condition of additional disease-free survival for 1 year,2 years,3 years,4 years,and 5 years,the corresponding 3-year cDFS of patients at ypTNM stage 0 were 96.97%,95.45%,96.92%,98.44%,100.00%,respectively.For ypTNM stage ? patients,the corresponding 3-year cDFS of patients at ypTNM ? were 68.22%,79.25%,86.32%,92.05%,96.43%,respectively.In patients with stage 0,the 8 years DFS was 94.03%,while the cDFS(3|5)was 100%,the difference value of 5.97%.The difference value of the corresponding ypTNM stage ?,ypTNM stage ?,ypTNM ? patients between 8 years DFS and cDFS(3|5)was 8.05%,18.55%and 41.70%,respectively.The more advanced ypTNM staging is,the more improvement the 3-year cDFS exhibits.Conclusions:The cDFS analysis was more able to reflect the dynamic changes in prognosis of rectal cancer patients with different ypTNM stages after NCRT,and there were significant differences due to different ypTNM stages.The 3-year cDFS of patients with stage 0 and ypTNM ? did not change significantly over time,while the 3-year cDFS of patients with ypTNM ? and ypTNM ? improved significantly over time.Patients with poorer ypTNM stage had greater improvement in cDFS.For patients with NCRT requiring long-term monitoring,cDFS analysis can help clinicians to better predict the prognosis of patients and develop reasonable follow-up strategies,Different follow-up plans should be adopted for patients with different ypTNM stages.For stage 0 and ypTNM stage ? patients,it is recommended to appropriately extend the follow-up interval,while for ypTNM stage ? and ypTNM stage ? patients,intensive follow-up strategy should be adopted to increase the follow-up density... |
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