Demographic and clinical characteristics of PSRCCR patients
A total of 11,515 patients were diagnosed with colorectal cancer from the hospital database between 1993 and 2018. Among them, 18 were identified with PSRCCR. The incidence of PSRCCR was 0.16 % in colorectal patients. A total of 72 patients with non-SRCC CRC were included as controls. PSRCCR patients was significant younger than non-SRCC CRC patients (mean age 50.2 vs 63 years-old, p < 0.001). In both the PSRCCR and non- SRCC groups, male predominance was noted (66.7 % vs 62.5 %, p =0.743). The baseline hypertension (22.2 % vs. 38.9 %, p = 0.186), diabetes mellitus (5.6 % vs. 16.7 %, p = 0.23), hyperlipidemia (0 % vs. 12.5%, p = 0.195), viral hepatitis (5.6 % vs. 5.6 %, p = 1), coronary artery disease (5.6 % vs. 11.1 %, p = 0.482) and chronic kidney disease (5.6 % vs. 9.7 %, p = 0.578), was comparable in these two groups. Most of the non-SRCC CRC patients were diagnosed by colonoscopy. In contrast, more than one-third PSRCCR patients were diagnosed by operation or non-colon site biopsy (p < 0.001). The PSRCCR group was associated with higher level of CEA (68.3 vs 17.7 ng/mL, p= 0.004), the albumin level was significantly lower in the PSRCCR group than in the non-SRCC group (3.4 vs 4.3 g/dL, p< 0.001). The clinical information of PSRCCR and non-SRCC CRC patients were summarized in Table 1.
Comparison of pathologic characteristics between PSRCCR and non- SRCC CRC patients
Majority of the tumor were located at left side in both groups (61.1 % vs 68.1 %, p= 0.586). Most tumor configuration of PSRCCR patients were ulcerating or infiltrative, whereas those of non-SRCC patients were exophytic or ulcerating (p< 0.001). The differentiation grade of PSRCCR group was significantly advanced than that of non-SRCC group (66.7 % vs 1.4 % high grade, p< 0.001). PSRCCR patients also had more lymphovascular invasion than non-SRCC patients (77.8 % vs 44.4 %, p= 0.011). The pathologic features were listed in Table 2.
Comparison of tumor stage between PSRCCR and non- SRCC CRC patients
Most of SRCC patients were diagnosed at stage T3 or T4 (94.4%) and N2 (77.8%). The distant metastasis rate was 50%. The only patient who was diagnosed with a tumor at an early stage, with carcinoma in situ, was due to a positive immunochemical fecal occult blood test during health examination. The number of the patients with initial AJCC stages 0 and 1, 2, 3, and 4 was 1 (5.6 %) versus 0 (0 %), 0 (0 %) versus 23 (31.9 %), 1 (5.6 %) versus 20 (27.8 %), 9 (50 %) versus 18 (25 %) and 7 (38.8 %) versus 11 (15.3 %) in the PSRCCR and non-SRCC groups, respectively (p = 0.001). All these CRC patients underwent operation. As most PSRCCR patients were diagnosed at advanced stage, 88.9% of them also received chemotherapy or combine therapy. In contrast, a curative resection (R0 resection with related radical lymphatic dissection) was performed in 37 (51.4 %) non-SRCC patients. The PSRCCR group had shorter follow-up period than non-SRCC group (15 vs 94.5 months, p < 0.001) (Table 3). The clinical characteristic of the 18 PSRCCR patients were listed in Table 4. Seventeen PSRCCR patients with initial computed tomography (CT) were reviewed. Most of the patients (14 of 17; 82.3 %) presented with long segmental wall thickening and increased enhancement of the involved colon. The average length of the thickened wall was 6.6 cm (range: 4.4–11.6 cm). Only 2 of the 17 (11.8 %) patients presented with an intraluminal mass. One patient (5.9 %) had carcinoma in situ, which could not be identified on CT.
Comparison of survival status between PSRCCR and non- SRCC CRC patients
The patients in the PSRCCR group had significantly poorer estimated overall survival than those in the Non-SRCC group (29.6 vs 162.7 months, log-rank p < 0.001, Fig. 1A). After stratification, the patients with PSRCCR had significantly poorer estimated overall survival than did the patients with non-SRCC of early stage CRC ((37 vs. 122.8 months, log-rank p < 0.001, Fig. 1B) and advanced stage CRC (18 vs. 140.7 months, log-rank p < 0.001, Fig. 1C). Since majority of the patients were diagnosed at advanced stage, most of them received chemotherapy and target therapy. Target therapy prescribed in this study included Cetuximab and Bevacizumab, and all non-SRCC CRC patients received Bevacizumab. Non-SRCC patients still had better prognosis than PSRCCR patients no matter which target therapy they used (Figure 2A). Target therapy treated or not didn’t improve the overall survival of PSRCCR patients (Figure 2B and C).
Factors associated with overall survival
In the univariable analysis of overall survival in all CRC patients, poor differentiation grade, lymphovascular invasion, advanced cancer stage, high CEA level and histological SRCC subtype were associated with increased mortality rates (all p < 0.05, Table 4). Further multivariate analysis with adjusted Cox proportional hazard model revealed that the CEA level (HR, 1.003; 95% CI, 1.000-1.005; p = 0.03) and histological SRCC subtype (HR, 8.333; 95% CI, 1.42-50; p = 0.005) were independent predictors of overall survival. The detail information of univariable and multivariate factor were listed in Table 5.