Rectal Location and Postcolonoscopy Colorectal Cancer Outcomes
Charles J. Kahi, Laura J. Myers, Patrick O. Monahan, Barry C. Barker, Timothy E. Stump, Thomas F. Imperiale
TL;DR
This study investigates if the location of colorectal cancer in the rectum affects survival outcomes after colonoscopy.
Contribution
The study introduces a focus on rectal cancer location as a potential factor in postcolonoscopy cancer outcomes.
Findings
Patients with rectal cancer had different survival outcomes compared to those with proximal cancers.
Cancer location may influence the effectiveness of colonoscopy in detecting and preventing colorectal cancer.
Abstract
This cohort study examines whether there are survival differences among patients with postcolonoscopy colorectal cancer based on cancer location.
Genes, proteins, chemicals, diseases, species, mutations and cell lines named across the full text — each resolved to its canonical identifier and authoritative record.
| Characteristic | Patients, No. (%) | |||||
|---|---|---|---|---|---|---|
| Overall (N = 14 205) | Rectal PCCRC-3y (n = 289) | Rectal DCRC (n = 4959) | Right PCCRC-3y (n = 999) | Right DCRC (n = 7958) | ||
| Age, y | ||||||
| Mean (SD) | 68.20 (9.01) | 68.12 (8.41) | 66.17 (8.88) | 69.85 (8.22) | 69.27 (8.98) | <.001 |
| Median (IQR) | 68.00 (61.00-76.00) | 67.00 (61.00-75.00) | 65.00 (60.00-73.00) | 70.00 (64.00-77.00) | 69.00 (62.00-77.00) | |
| Range | 50.00-85.00 | 51.00-85.00 | 50.00-85.00 | 50.00-85.00 | 50.00-85.00 | |
| Age group, y | ||||||
| ≥65 | 8582 (60.4) | 172 (59.5) | 2505 (50.5) | 714 (71.5) | 5191 (65.2) | <.001 |
| <65 | 5623 (39.6) | 117 (40.5) | 2454 (49.5) | 285 (28.5) | 2767 (34.8) | |
| Sex | ||||||
| Male | 13935 (98.1) | 286 (99.0) | 4891 (98.6) | 977 (97.8) | 7781 (97.8) | .004 |
| Female | 270 (1.9) | 3 (1.0) | 68 (1.4) | 22 (2.2) | 177 (2.2) | |
| Race | ||||||
| White | 11508 (81.0) | 239 (82.7) | 4157 (83.8) | 831 (83.2) | 6281 (78.9) | <.001 |
| Black | 2413 (17.0) | 43 (14.9) | 703 (14.2) | 150 (15.0) | 1517 (19.1) | |
| Additional groups | 284 (2.0) | 7 (2.4) | 99 (2.0) | 18 (1.8) | 160 (2.0) | |
| Indicator for Hispanic ethnicity | ||||||
| No | 13385 (94.2) | 269 (93.1) | 4670 (94.2) | 948 (94.9) | 7498 (94.2) | .67 |
| Yes | 820 (5.8) | 20 (6.9) | 289 (5.8) | 51 (5.1) | 460 (5.8) | |
| Weighted Charlson score | ||||||
| Mean (SD) | 2.38 (2.64) | 2.23 (2.31) | 1.82 (2.30) | 3.04 (2.94) | 2.65 (2.74) | <.001 |
| Median (IQR) | 2.00 (0.00-3.00) | 2.00 (1.00-3.00) | 1.00 (0.00-3.00) | 2.00 (1.00-4.00) | 2.00 (1.00-4.00) | |
| Range | 0.00-18.00 | 0.00-12.00 | 0.00-18.00 | 0.00-17.00 | 0.00-17.00 | |
| Statin use | ||||||
| No | 8549 (60.2) | 152 (52.6) | 3347 (67.5) | 437 (43.7) | 4613 (58.0) | <.001 |
| Yes | 5655 (39.8) | 137 (47.4) | 1612 (32.5) | 562 (56.3) | 3344 (42.0) | |
| NSAID use | ||||||
| No | 12522 (88.2) | 240 (83.0) | 4373 (88.2) | 854 (85.5) | 7055 (88.7) | .001 |
| Yes | 1682 (11.8) | 49 (17.0) | 586 (11.8) | 145 (14.5) | 902 (11.3) | |
| Aspirin use | ||||||
| No | 10476 (73.7) | 204 (70.6) | 3937 (79.4) | 622 (62.3) | 5713 (71.8) | <.001 |
| Yes | 3728 (26.2) | 85 (29.4) | 1022 (20.6) | 377 (37.7) | 2244 (28.2) | |
| Family history of CRC | ||||||
| No | 13914 (98.0) | 285 (98.6) | 4861 (98.0) | 975 (97.6) | 7793 (97.9) | .71 |
| Yes | 290 (2.0) | 4 (1.4) | 98 (2.0) | 24 (2.4) | 164 (2.1) | |
| Current smoker | ||||||
| No | 8738 (61.5) | 167 (57.8) | 2759 (55.6) | 652 (65.3) | 5160 (64.8) | <.001 |
| Yes | 5466 (38.5) | 122 (42.2) | 2200 (44.4) | 347 (34.7) | 2797 (35.1) | |
| AJCC cancer stage | ||||||
| I | 4825 (34.0) | 114 (39.4) | 1854 (37.4) | 358 (35.8) | 2499 (31.4) | <.001 |
| II | 3990 (28.1) | 70 (24.2) | 1232 (24.8) | 251 (25.1) | 2437 (30.6) | |
| III | 3242 (22.8) | 67 (23.2) | 1083 (21.8) | 217 (21.7) | 1875 (23.6) | |
| IV | 2148 (15.1) | 38 (13.1) | 790 (15.9) | 173 (17.3) | 1147 (14.4) | |
| Chemotherapy | ||||||
| No | 8353 (58.8) | 122 (42.2) | 1911 (38.5) | 707 (70.8) | 5613 (70.5) | <.001 |
| Yes | 5852 (41.2) | 167 (57.8) | 3048 (61.5) | 292 (29.2) | 2345 (29.5) | |
| Radiation therapy | ||||||
| No | 11253 (79.2) | 132 (45.7) | 2224 (44.8) | 991 (99.2) | 7906 (99.3) | <.001 |
| Yes | 2952 (20.8) | 157 (54.3) | 2735 (55.2) | 8 (0.8) | 52 (0.7) | |
| Immunotherapy | ||||||
| No | 14116 (99.4) | 286 (99.0) | 4927 (99.4) | 993 (99.4) | 7910 (99.4) | .74 |
| Yes | 89 (0.6) | 3 (1.0) | 32 (0.6) | 6 (0.6) | 48 (0.6) | |
| Surgery | ||||||
| No | 2204 (15.5) | 71 (24.6) | 1374 (27.7) | 93 (9.3) | 666 (8.4) | <.001 |
| Yes | 12001 (84.5) | 218 (75.4) | 3585 (72.3) | 906 (90.7) | 7292 (91.6) | |
| Comparison | Univariable | Multivariable | ||||
|---|---|---|---|---|---|---|
| Excluding stage variable from model | Including stage variable in model | |||||
| HR (95% CI) | HR (95% CI) | HR (95% CI) | ||||
|
| ||||||
| All cause | 1.22 (1.06-1.41) | .005 | 1.10 (0.96-1.27) | .17 | 1.13 (0.98-1.30) | .09 |
| CRC specific | 1.10 (0.91 1.34) | .32 | 1.06 (0.87-1.29) | .54 | 1.09 (0.90-1.33) | .38 |
|
| ||||||
| All cause | 1.15 (0.98-1.34) | .08 | 0.96 (0.77-1.20) | .72 | 1.13 (0.91-1.42) | .27 |
| CRC specific | 1.41 (1.13-1.76) | .003 | 0.97 (0.70-1.36) | .87 | 1.26 (0.90-1.76) | .17 |
|
| ||||||
| All cause | 1.06 (1.02-1.11) | .006 | 1.01 (0.95-1.07) 1.02 | .75 | 1.07 (1.01-1.14) | .03 |
| CRC specific | 1.40 (1.31-1.49) | <.001 | 0.99 (0.91-1.08) | .84 | 1.11 (1.01-1.21) | .03 |
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Taxonomy
TopicsColorectal Cancer Screening and Detection · Colorectal Cancer Surgical Treatments · Gastric Cancer Management and Outcomes
Introduction
Postcolonoscopy colorectal cancers (PCCRCs; ie, cancers that are diagnosed after a colonoscopy that did not detect cancer) are a core measure of colonoscopy quality.^1,2^ Our group has previously reported a PCCRC prevalence of 6% in the Veterans Health Administration (VHA).^3^ PCCRCs have a higher predilection for the proximal colon, but recent evidence shows that the rectum is one of the most common locations when the colorectum is stratified into its individual segments.^4,5^ This is important because rectal cancer has specific features that differ from cancer elsewhere in the colon, including a higher propensity for locoregional invasion. To our knowledge, no studies have assessed whether rectal location is associated with cancer-specific mortality (CSM) and all-cause mortality (ACM) among patients with CRC detected 6 months to 3 years after colonoscopy (PCCRC-3y).
Methods
The cohort study was approved as exempt research by the institutional review boards at Indiana University and by the Research and Development Committees of the Richard L. Roudebush VA Medical Center in Indianapolis, Indiana. The institutional review board approved a waiver of informed consent given the retrospective cohort design. The study followed the (STROBE) reporting guideline.
We conducted a secondary analysis of a VHA-Medicare administrative database that includes veterans with CRC diagnosed between January 1, 2003, and December 31, 2013. Patients whose colonoscopy occurred 6 months or less before CRC diagnosis were defined as detected CRC (DCRC), and those whose colonoscopy occurred 6 to 36 months prior to CRC diagnosis as PCCRC-3y.^3^ Individuals were censored at the time of death or December 31, 2018. We used Cox proportional hazards regression to model the time to ACM and CSM after CRC diagnosis. The analyses were stratified by location (rectum or right colon [cecum, ascending colon, transverse colon]) and whether the patient was classified as PCCRC-3y or DCRC.
R version 4.2.1 (R Foundation for Statistical Computing) was used for all analyses. Final analyses were performed in February 2025. Covariates with a 2-sided P ≤ .15 were included in multivariable models, and P < .05 was considered statistically significant.
Results
Among 5248 rectal cancers, 289 (5.5%) were classified as PCCRC-3y and 4959 (94.4%) as DCRC. Demographic and clinical features are summarized in Table 1. Based on multivariable Cox proportional hazards analysis (Table 2), there was no significant difference in ACM and CSM between rectal PCCRC-3y and rectal DCRC, with adjusted hazard ratios (aHRs) of 1.13 (95% CI, 0.98-1.30; P = .09) and 1.09 (95% CI, 0.90-1.33; P = .38), respectively. There were also no significant differences in ACM and CSM between rectal PCCRC-3y and right colon PCCRC-3y (Table 2). There was a statistically significant, but numerically modest, higher ACM and CSM for rectal DCRC compared with right colon DCRC.
Discussion
We found comparable ACM and CSM between rectal PCCRC-3y and DCRC and between rectal PCCRC-3y and right colon PCCRC-3y. Overall, rectal location and classification as PCCRC-3y or DCRC appeared to have minimal to no impact on mortality after CRC diagnosis. These findings align with those of most studies assessing PCCRC-3y outcomes, although recent work suggests that conventional survival analyses of PCCRC are susceptible to lead time and immortal time biases.^6^ Additional study with PCCRCs defined after index colonoscopy is warranted.
The rectum has long been identified as an area that is prone to missed colorectal neoplasms. These are often located on the proximal side of the valves of Houston and can escape detection without careful examination. The association of PCCRCs with proximal colonic location has contributed to the current recommendation to perform a second examination of the right colon. However, this should not be at the detriment of other areas of the colon, and the fact that the rectum is a common location for PCCRC underscores the importance of meticulous and repeated inspection of this area.
Limitations of our study include missing or limited data on certain covariates (body mass index, physical activity, colonoscopy quality), potentially incomplete capture of colonoscopies done outside the VHA, and residual confounding. Our findings should be validated in more contemporary samples, ideally coupled with root-cause analyses to determine the factors contributing to the burden of rectal PCCRC.
The reference list from the paper itself. Each links out to its DOI / PubMed record.
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- 6Kang JH, Jensen CD, Merchant SA, Lee JK. Lead time and immortal time biases impact the calculation of post-colonoscopy colorectal cancer survival. Clin Gastroenterol Hepatol. 2024;22(12):2529-2531.e 7. doi:10.1016/j.cgh.2024.05.01438782174 · doi ↗ · pubmed ↗