This retrospective cohort study evaluated survival outcomes and prognostic factors in patients diagnosed with CRC at the CNDTCG in Cartago, CR, between January 1, 2020, and December 31, 2021. The study included all consecutive patients with biopsy-confirmed CRC recorded in the institutional pathology registry during this period. Cases with incomplete clinical or pathological data or without histological confirmation were excluded.

The study was approved by the Scientific Ethics Committee under protocol number HNN-DG-CEC-045-2025. All data were anonymized before analysis, and confidentiality was maintained in accordance with national regulations.

Clinical and pathological data were extracted from biopsy reports and hospital medical records. Data were entered into an Excel 97-2003 spreadsheet and analyzed using Stata version 18. Variables with missing values were analyzed by complete-case analysis; no data imputation was performed.

Demographic variables included age, sex, and canton of residence. Clinical variables comprised symptoms at diagnosis (e.g., rectal bleeding, abdominal pain, weight loss), tumor localization, and TNM stage (6th edition). Tumor location was classified as right colon (cecum, ascending colon, hepatic flexure), left colon (descending colon, sigmoid colon), rectum, or anal canal/anus.

Treatment variables included type of surgical procedure (colectomy, colostomy, low anterior resection [LAR], abdominoperineal resection [APR], sigmoidectomy) and surgical approach (laparoscopic vs. open). Adjuvant therapy regimens included capecitabine monotherapy, FOLFOX, XELOX, chemoradiotherapy, and bevacizumab-based combinations. Postoperative complications were recorded and categorized by severity.

Lymph node involvement was classified as: none (0), low (1 - 3 nodes), moderate (4 - 6 nodes), or high (≥7 nodes). TNM stages were grouped into:

1) Early (Localized): Tis, T1, or T2; N0; M0.

2) Regional: T3, T4, N1, or N2; M0.

3) Advanced (Metastatic): M1, regardless of T or N.

4) Unclassified/Unknown: incomplete or missing TNM data.

The primary outcome was overall survival, defined as time from diagnosis to death from any cause or last follow-up. Disease-free survival was analyzed where applicable.

Categorical variables were summarized as frequencies and percentages, and continuous variables as means with standard deviations or medians with interquartile ranges. Kaplan–Meier curves were generated to estimate survival probabilities. Cox proportional hazards regression was used to evaluate associations between prognostic variables and survival, reporting hazard ratios (HR) with 95% confidence intervals (CI).

Three models were constructed:

Model 1: adjusted for age, sex, and place of residence.Model 2: additionally adjusted for treatment variables.Model 3: included interaction terms between TNM stage and treatment.

Time-dependent Cox models were applied to evaluate changes in treatment effects over time. Chi-square tests compared observed versus expected events across tumor locations. A p-value < 0.05 was considered statistically significant.

Thirty-six patients (35.64%) were diagnosed through FIT screening, and 65 (64.36%) through other means. FIT-detected cases were more frequently diagnosed at early stage (41.67% vs. 6.25%), while non-FIT cases were more often regional (51.56%) or advanced (29.69%) (Table 2).

Table 2. Screening methods versus stages.

Tumor location was most frequently the rectum (45.54%), followed by the right colon (26.73%), left colon (24.75%), and anal canal (2.97%) (Table 3). TNM staging showed 45% regional disease, 22% metastatic, 19% localized, and 14% unclassified. Adenocarcinoma was the predominant histology (91.09%), with less frequent types including intramucosal carcinoma (3.96%), signet-ring cell carcinoma (1.98%), and other subtypes (2.97%).

Table 3. Tumor characteristics.

Rectal cancer was commonly diagnosed at regional (56.52%) or advanced (26.09%) stages. Early-stage tumors were more frequent in the left colon (32%) and right colon (23.08%) (Table 4). Unclassified staging was more common in the right colon (26.92%), likely due to incomplete data.

The chi-square test showed a marginally non-significant difference in mortality distribution by location (χ² = 6.95, p = 0.0736). Rectal cancer mortality matched expectations (observed: 21; expected: 22.90), whereas right colon had more deaths than expected (15 vs. 9.89), and left colon fewer (7 vs. 11.86).

Table 4. Localization by Stage TNM.

Surgery was performed in 75.25% of patients; colectomy (25.74%), colostomy (19.80%), and LAR (17.82%) were most common. Laparoscopic surgery was used in 40.59% of cases. Postoperative complications occurred in 21.78% of patients. Adjuvant therapy was given to 46.53%, most frequently FOLFOX/XELOX (23.76%), capecitabine monotherapy (6.93%), and chemoradiotherapy (6.93%) (Table 5).

Table 5. Treatments.

Low Anterior Resection (LAR), Abdominoperineal Resection (APR).

Early-stage tumors had better survival (HR: 0.10, 95% CI: 0.02 - 0.52, p = 0.00) than unclassified cases. Localized disease showed a protective trend (HR: 0.45, 95% CI: 0.18 - 1.08, p = 0.07), while advanced disease had worse prognosis (HR: 1.76, 95% CI: 0.73 - 4.23, p = 0.20) (Table 6, Figure 1).

Table 6. Cox regression models.

FIT-based diagnosis was strongly associated with improved survival (HR: 0.24, 95% CI: 0.11 - 0.54, p = 0.001; log-rank p = 0.0001) (Table 6, Figure 2). Left-sided CRC had significantly better survival than right-sided (HR: 0.38, 95% CI: 0.15 - 0.94, p = 0.03) (Figure 3).

Figure 1. Kaplan Meier survival rates by TNM.

Figure 2. Kaplan Meier survival rates by FIT status.

Figure 3. Kaplan Meier survival rates by tumor localization.

Time-dependent Cox models showed initial strong survival benefits for colectomy (HR: 0.027, p = 0.007), colostomy (HR: 0.032, p = 0.004), and APR (HR: 0.00008, p = 0.023), but these effects diminished or reversed over time, suggesting late complications or reduced benefit.

Chemotherapy regimens also showed early benefit but declining effects:

FOLFOX/XELOX: early HR 0.67 (p = 0.017) → later HR 6.92 (p = 0.001)Chemoradiotherapy: early HR 0.012 (p = 0.081) → later HR 9.68 (p = 0.013)Bevacizumab: early HR 0.008 (p = 0.147) → later HR 10.07 (p = 0.047)

When analyzed overall, FOLFOX/XELOX was associated with higher mortality (HR: 2.82, 95% CI: 1.44 - 5.53, p = 0.00), likely reflecting its use in advanced cases rather than intrinsic inefficacy (Table 7).

Table 7. Time-dependent cox regression models for surgical and chemotherapy treatments.

Val.: Values, Qx-Rx: Chemoradiotherapy.

Patients diagnosed with FIT screening were more likely to have early-stage disease (41.67% vs. 6.25%) compared with those diagnosed through other pathways, consistent with previous studies reporting improved early detection and reduced mortality through FIT programs [6]-[9]. Although the hazard ratio for mortality among FIT-detected cases did not reach statistical significance (HR: 0.88, p = 0.726), the limited sample size may have reduced statistical power. Conversely, patients diagnosed outside FIT programs had a markedly worse prognosis (HR: 5.56, p < 0.001), reinforcing the established association between late-stage diagnosis and poor survival [10][11]. Strengthening FIT-based screening coverage and adherence could increase early detection rates and improve long-term outcomes.

Rectal cancer was the most frequent location (45.54%), contrasting with patterns from high-income countries where left-sided CRC predominates [12][13]. This could reflect genetic, environmental, or healthcare access differences in CR. Rectal tumors were often diagnosed at regional (56.52%) or advanced (26.09%) stages, underscoring possible diagnostic delays or aggressive biology. Left-sided CRC showed significantly better survival (HR: 0.38, p = 0.03) than right-sided tumors, aligning with evidence that right-sided CRC is less responsive to standard treatments [14]-[16]. Although differences in survival by location did not reach statistical significance (log-rank p = 0.0736), trends support the relevance of anatomical site in prognosis and treatment planning.

Surgery remained a strong determinant of survival. Colectomy, low anterior resection, and sigmoidectomy were associated with improved outcomes, with laparoscopic surgery showing a protective effect (HR: 0.48, p = 0.02), in line with literature on the benefits of minimally invasive techniques [17]. Time-dependent analysis revealed that initial survival benefits of colectomy and colostomy diminished over time, suggesting possible late complications or reduced efficacy in advanced disease.

Adjuvant therapy demonstrated time-dependent benefits, with protective effects increasing during follow-up (HR: 1.54, p = 0.004). However, FOLFOX/XELOX regimens were associated with worse overall survival (HR: 2.82, p = 0.00), likely due to indication bias as these regimens are often used in advanced cases. This underlines the importance of patient stratification and individualized therapy [18].

Neither lymph node involvement nor postoperative complications significantly affected survival in this cohort, suggesting that other factors—such as tumor biology and systemic inflammation—may have greater prognostic weight.

The high proportion of late-stage rectal cancer cases supports revising screening strategies to improve detection in this location. Surgical decisions should consider both stage and patient characteristics, while structured follow-up programs could maximize the time-dependent benefits of adjuvant therapy.

Further studies should explore molecular differences between right- and left-sided CRC, integrate tumor location into risk models, and assess novel therapeutic approaches including neoadjuvant and immunotherapy. Large-scale, prospective research is needed to validate these findings and guide personalized CRC management in CR.