| Objective: We retrospectively analyzed the clinicopathological characteristics of patients with tumor deposit-positive colorectal cancer,evaluated the predictive role of tumor deposit in the prognosis of colorectal cancer and the weight of staging,and based on this,proposed optimal clinical staging proposals incorporating tumor deposit as an important consideration to provide a basis for the precise treatment of colorectal cancer patients.Methods: A total of 2642 patients with colorectal cancer(CRC)and positive tumor deposit(TD)were collected from our hospital from January 2013 to March 2021.TD(-)CRC patients were matched according to the characteristics of the same period(enrollment time difference ≤ 1 month)and diagnosis,treatment plans as the control group,with a total of 1162 cases.The deadline for follow-up is February 20,2023,with a median follow-up time of 37 months [23 months,61 months].Compare the clinical and pathological characteristics of patients with TD(+)and TD(-)in stages I-III and stage IV of simultaneous metastasis.Compare the overall survival time(OS)and 1-year,3-year,and 5-year OS rates of stage I-IV TD(+)and TD(-)CRC patients,compare the disease free survival time(DFS)and 1-year,3-year,and 5-year DFS rates of stage I-III TD(+)and TD(-)CRC patients,and compare the disease progression free survival time(PFS)and 1-year DFS rates of stage IV TD(+)and TD(-)CRC patients Analyze the difference in PFS rates between 2 and 3 years,analyze the value of TD(+)in the prognosis of CRC patients,and clarify the value of TD number in the prognosis of CRC.Compare the impact of TD positivity and its quantity on prognosis in different T,N,and M stages,evaluate the weight of TD participation in the clinical staging system,and based on this,consider TD as a new important factor in clinical staging,and propose new suggestions for optimizing the 8th edition AJCC TNM staging system.SPSS 25.0 software was used for data analysis,and chi square test was used to compare the classification data between groups.COX univariate and multivariate analysis was conducted to identify the risk factors affecting the prognosis of CRC.Using X-Tile software to calculate the cutoff value of the number of cancer nodules and compare the prognosis differences of patients under different numbers of cancer nodules.Kaplan Meier curve was used for survival analysis,and Log Rank analysis was used to compare the survival curves,P <0.05 was recorded as statistically significant.Results: 1、Clinical and pathological characteristics of TD(+)patients:(1)A total of 11,349 patients underwent colon and rectal surgery in our hospital from January 2013 to December 2021,and the postoperative pathology was clearly diagnosed as CRC,including 2,871 patients with TD(+),and the positive rate of tumor deposits was 25.3%(2,871/11,349).(2)Comparison of clinicopathological features between patients with stage IIII TD(+)and TD(-)CRC: compared with TD(-)patients,primary foci in TD(+)patients were more often located in the left hemicolectum and rectum(79.6% vs.73.0%,P <0.001);T-stage was more advanced(T3+T4: 97.1% vs.78.8%,P <0.001);regional metastatic lymph nodes(lymph node,LN)were more numerous(LN>3: 31.7% vs 7.3%,P <0.001);primary foci were more often hypofractionated,more often with nerve invasion and vascular infiltration(all P<0.05);and d MMR rates were lower in TD(+)patients(3.2%vs8.4%,P <0.001).(3)Comparison of clinicopathological characteristics between patients with concurrent metastatic stage IV TD(+)and TD(-)CRC: Compared with TD(-)patients,TD(+)patients had a more advanced T-stage of primary foci,a higher number of LN(+),and were more likely to have concurrent metastases at ≥2 sites(all P <0.05).However,there were no statistically significant differences between TD(+)and TD(-)patients in terms of gender,age size,primary site,tumor with nerve invasion,and degree of tumor differentiation(P >0.05).(4)There were 6 cases of colon and rectal neuroendocrine carcinoma in this study,and all of them were positive for cancer nodes.2、Prognosis of TD(+)CRC patients(1)The OS of TD(+)patients is shorter than that of TD(-)patients(m OS: 51 months vs 108 months,P =0.000).(2)Patients with TD(+)after stage I-III radical surgery have shorter OS and DFS compared to TD(-)(3-year OS rate: 67.9% vs 85.0%,P =0.000,3-year DFS rate: 50.2% vs 79.4%,P =0.000).(3)There was no significant difference in OS between TD(+)and TD(-)patients with simultaneous metastasis stage IV(m OS 18 months vs 24 months,P =0.890),and TD(+)had a shorter PFS compared to TD(-)patients(3-year PFS rate: 8.8% vs 15.2%,P =0.049).(4)In patients with stage I-III CRC,the more TD,the worse the prognosis.The m OS of patients with TD=0,TD=1,TD=2,TD=3,TD=4,and TD ≥ 5 were 118 months,68 months,66 months,47 months,38 months,and 33 months,respectively(P =0.000).Patients with TD ≥ 5 had the shortest survival time.(5)Analysis of the correlation between TD positivity and the prognosis of CRC patients: Among stage I-III patients,TD(+)is one of the independent risk factors affecting OS and DFS in colorectal cancer patients(OS: HR=2.467,95% CI: 1.071-2.008,P =0.017;DFS: HR=2.046,95% CI: 1.552-2.698,P <0.001).3、Analysis of the weighting of TD in the TNM staging system and the value of optimizing clinical staging(1)Analysis of the weight and optimized clinical staging value of TD and TD number in N staging: 1)There was no significant difference in survival between TD(+),LN(-)and TD(-),LN(+)patients(3-year OS rate: 75.4% vs 75.4%,P =0.418).2)The prognosis of N1 c patients is worse than that of N2 a,TD(-)patients(3-year OS rate: 75.4% vs 85.0%,P =0.029).The prognosis of N1 c patients is better than that of N2 b,TD(-)patients(3-year OS rate: 75.4% vs 45.0%,P =0.034).3)There was no significant difference in survival between N1c(TD ≤ 2)patients and N2 a,TD(-)patients(P =0.071);There was no significant difference in survival between N1c(TD>2)and N2 b,TD(-)patients(3-year OS rate: 77.0% vs 45.0%,P =0.392),but survival was worse than that of N2 a,TD(-)groups(P =0.024).4)Counting TD and LN together for N staging,plotting ROC curve with AUC area=0.613(95% CI: 0.582-0.644,p<0.001).(2)Weight analysis of TD and TD number in M staging 1)The OS of TD(+)and M0 patients was longer than that of M1 and TD(-)patients(3-year OS rates: 67.9%,23.6%,P<0.001).2)There was no significant difference in survival between patients with TD>4,LN(-)and M1,TD(-)(P =0.061).Classify TD>4 and M0 as M1 stages and plot ROC curves with AUC area=0.616(95% CI: 0.585-0.647,P <0.001).3)There was no significant difference in survival between N2 b and TD(+),M0,and M1,TD(-)patients(2-year OS rate: 53.7% vs 53.7%,P =0.554).Patients with N2 b,TD(+),and M0 were classified into M1 stage and ROC curves were plotted with AUC area=0.604(95% CI: 0.574-0.635,P <0.001).Conclusions: 1、The positive rate of tumor deposit in colorectal cancer patients in our hospital is 25.3%.2、CRC patients with TD(+)are associated with more adverse prognostic factors.In stage I-III patients,TD(+)patients have a later T-stage of the primary lesion,a higher number of LN(+),more often located in the left colon or rectum,poor tissue differentiation,susceptibility to nerve invasion and vascular infiltration,and a higher preoperative carcinoembryonic antigen(P <0.05).In patients with stage IV simultaneous metastasis,TD(+)patients have a later T-stage of the primary lesion,a higher number of LN(+),a higher likelihood of vascular infiltration,and a higher likelihood of multiple site metastases simultaneously(P <0.05).3、Among patients with stage I-III CRC,the d MMR rate of TD(-)patients is higher than that of TD(+)patients.4、There were a total of 6 patients with neuroendocrine carcinoma of the colon and rectum,all of whom were positive for TD,indicating that this malignant neuroendocrine carcinoma with poor biological behavior may have a high TD positive rate.5、Both TD and the number of TD can affect the prognosis of CRC patients.6、The current TNM staging system underestimates the prognostic weight of tumor deposit in colorectal cancer,and further improvement is needed.Based on the research results,we propose the following suggestions for optimizing the 8th version of TNM staging system:(1)TD and LN can be considered to be counted together for N staging;(2)Regardless of the N stage,when the prognosis of patients with TD>4 is similar to that of M1 stage patients,it can be considered as M1 stage;(3)When the number of LN is ≥ 7,the prognosis of patients with positive cancer nodules(regardless of their number)is similar to that of M1 stage patients,and can be considered as M1 stage. |
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