A total of 169 newly diagnosed rectal cancer patients who underwent neoadjuvant chemo-radiation therapy and surgery were included in the study. Overall, 30 (17.8%) patients achieved PCR and 103 (60.9%) patients displayed downstaging. In addition, the average age at diagnosis was 58.4±13.2 years old, and 67.2% (117/174) were male. The majority of patients in the analysis were diagnosed with clinical stage II (29%) and clinical stage III (71%) cancer. Among those patients, the rate of PCR and downstaging were 18% and 65%, respectively. Additionally, of the four patients showing no PCR but (y) p stage 0, the (y)pT stage was found carcinoma in situ (Tis).
As a result, there was a statistically significant difference between the PCR and no PCR group among the histology type of adenocarcinoma (p=0.034) and lymph-vascular invasion (p<0.001). However, there were no statistically significant difference in age at diagnosis, sex, BMI, tumor staging, distance from anal verge, surgery type, ASA classification, the type of neoadjuvant chemotherapy regimen, pre and post nCRT CEA status, and pre-nCRT Hb level between patients with PCR or no PCR (all p> 0.05) (table 1). Moreover, there was a significant difference between the downstaging group and non-response group in clinical stage, clinic N stage, CRM, and lymph-vascular invasion.
PCR and downstaging for survival and disease recurrence outcome
The mean duration of survival among the PCR group was 12 months longer than the no PCR group, which is statistically significant (p= 0.010); also, the mean time of disease recurrence following surgery was 17 months longer in the PCR group than the no PCR group (p= 0.001). According to the results of Kaplan-Meier analysis, the PCR group had better survival benefits, to a level of statistical significance, both in overall survival and disease recurrence free survival than the no PCR group with p values of 0.033 and 0.025, respectively (Figure 1A and 1B). Moreover, the group displaying downstaging also demonstrated significantly better overall survival benefits and disease recurrence free survival benefits than the group without a downstaging response (both p values were <0.001) (Figure 1C and 1D).
Further, between the mortality and survivor groups, there were significant differences in age, sex, clinical stage, pre-nCRT Hb level, pre-nCRT and post-nCRT CEA level, lymph vascular invasion, time to survival and disease recurrence, surgery type, ASA classification, CAP regression grade, received adjuvant chemotherapy (all p< 0.05) (Table 2). Distance from the anal verge was marginally but still significantly lower in the recurrence population (5.67 ± 2.77 cm) than the non-recurrence patients (4.68 ± 2.35 cm). Among the recurrence group, there were significantly more patients who received adjuvant chemotherapy than the non-recurrence group (62.16%).
Associated factors of tumor response
According to the results of multivariate logistic regression, the histology type of adenocarcinoma appeared to be the only predictive factor of PCR when controlling other clinical factors [adjusted Odds ratio (aOR): 5.385, 95% Confidence Interval (CI): 1.27-22.9, p-value=0.023, AUC: 0.55]. Moreover, after controlling other clinical factors, a positive clinical N stage was associated with the downstaging rate (aOR: 3.458, 95%CI: 1.77-6.73, p-value<0.001, AUC: 0.63). However, various clinical factors, including age, sex, BMI, regimen of chemotherapy or radiation therapy, CEA concentration levels and Hb level, as well as tumor size, had no statistically significant association with PCR or downstaging (Table 3).
Further, patients with PCR were 2.9 times more likely to survive (OR: 2.91, 95% CI: 0.96-8.86) than the residual group. Patients with downstaging were 3.2 times more likely to survive (OR: 3.26, 95% CI: 1.62-6.54) and less likely to have disease recurrence (OR: 2.79, 95% CI: 1.29-5.92] than the non-response group (Table 3).
Risk factors and protective factors of outcomes
After controlling the confounding variables, downstaging was revealed to be the important protective factor for survival [adjusted hazard ratio (aHR): 0.40, 95% CI: 0.21-0.71] in female patients (aHR: 0.42, 95%CI: 0.12-0.88). In addition, the multivariate Cox proportional analysis selected variables of the abnormal post CEA level (aHR:1.91, 95%CI:1.05-3.48) , and abnormal pre-nCRT Hb level (aHR: 2.54, 95% CI: 1.41-4.58) as risk factors of survival among rectal cancer patients (Table 4). Similarly, downstaging also appeared to be the important protective factor of disease recurrence after controlling all the confounding variables (aHR: 0.42, 95% CI: 0.21-0.82). In addition, patients who received adjuvant chemotherapy were 65% less likely to relapse (aHR: 0.35, 95% CI: 0.18-0.69) (Table 5).