Non-operative management of rectal adenocarcinoma in a safety-net system: a decade of real-world outcomes outside watch-and-wait eligibility
Ashley N. Chavana1
, Piyush Pathak2, Caleb Stewart2, Laurynn Garcia3, Alfredo Echeverria2, Eric Silberfein4, Cary Hsu4, Benjamin Musher5, Alexander N. Hanania2
Abstract: Recent guidelines increasingly support watch-and-wait (W&W) strategies for locally advanced rectal cancer (LARC) following favorable response to neoadjuvant therapy. However, these strategies have largely been validated in highly selected trial populations and require intensive surveillance that may be difficult to implement in underserved settings. Limited data exist on outcomes among patients affected by adverse social determinants of health, particularly in safety-net hospital systems. We evaluated outcomes of patients with LARC in an underserved setting who were managed non-operatively out of necessity, rather than according to W&W guidelines. Most of the presented cohort would not have met eligibility criteria for contemporary W&W trials and received care that largely predated widespread adoption of W&W, allowing assessment of whether comparable outcomes are achievable in a higher-risk, real-world population. This retrospective study included patients with LARC managed non-operatively with definitive intent at a single safety-net hospital system over a decade. All patients received radiotherapy and systemic chemotherapy. Clinical characteristics, treatment details, and oncologic outcomes were abstracted. Forty-nine patients were identified with a median follow-up of 25 months (range, 8–90 months). The cohort was 55% male and racially/ethnically diverse (63% Hispanic, 20% White, 12% Black). Most patients (69%) were uninsured. Reasons for non-operative management included patient preference (49%), suspicion of low-burden metastatic or non-regional nodal disease (35%), and medical comorbidities (16%). The majority (76%) received long-course chemoradiotherapy (50–55 Gy with concurrent capecitabine); the remainder received short-course radiotherapy (25 Gy/5 fractions). Local failure did not differ significantly between regimens (P=0.51). Two-year local control, progression-free survival, and overall survival were 59%, 43%, and 67%, respectively. Eighteen patients (37%) achieved an initial complete or near-complete clinical response, of whom 5 developed local recurrence. Distant-only metastasis was the most common recurrence pattern. Despite inclusion of higher-risk patients who would not meet standard W&W criteria, radiotherapy-based non-operative management achieved meaningful local control, with regrowth rates among responders comparable to prospective trials. These findings support the feasibility of organ-preserving approaches in safety-net populations even when adherence to W&W surveillance protocols remains challenging.
Keywords: Rectal adenocarcinoma; non-operative management; watch-and-wait (W&W); radiation therapy (RT); health disparities
Submitted May 08, 2026. Accepted for publication Jul 01, 2026. Published online Jul 09, 2026.
doi: 10.21037/jgo-2026-0491
Locally advanced rectal cancer (LARC) has traditionally been managed with multimodal therapy consisting of neoadjuvant chemoradiotherapy or total neoadjuvant therapy (TNT), followed by total mesorectal excision (TME) and adjuvant chemotherapy (1-6). Evolving paradigms increasingly support non-operative management for selected patients who achieve a complete clinical response (cCR) following neoadjuvant therapy (7,8). The OPRA trial demonstrated that TNT followed by a watch-and-wait (W&W) approach allowed approximately 50% of patients to avoid surgery, with most local regrowth events occurring within two years of treatment completion (7).
Successful W&W depends on intensive surveillance with serial imaging, endoscopy, and clinical examinations to detect local regrowth early. However, adherence to recommended surveillance is challenging even in well-resourced settings, with most patients failing to meet full National Comprehensive Cancer Network (NCCN)-recommended follow-up over time (9). This challenge is amplified in safety-net systems, where patients face barriers related to insurance status, access to specialty care, transportation, language, and competing social needs. Collectively, these factors contribute to more advanced disease at presentation and delays in care among uninsured and underinsured colorectal cancer patients universally (10-12).
Patients enrolled in prospective W&W trials such as OPRA or JANUS are highly selected, requiring close evaluation for a complete or near-cCR and the capacity to adhere to rigorous surveillance. In contrast, many patients treated in safety-net systems are managed non-operatively out of necessity, often due to comorbidities, advanced or metastatic disease, advanced age, socioeconomic barriers, or patient preference. These patients would not meet eligibility criteria for contemporary W&W strategies, and outcomes in this group remain poorly defined. Characterizing them is essential to inform whether non-operative management can be ethically extended to populations outside contemporary trial criteria, particularly when surgery is not a feasible option. In this context, we retrospectively evaluated outcomes in patients with LARC managed non-operatively at a safety-net hospital system, focusing on (I) the efficacy of radiation therapy (RT) in maintaining local control (LC) and (II) treatment-related adverse events in an underserved, real-world population. We present this article in accordance with the STROBE reporting checklist (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0491/rc).
The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Ethics Board of Baylor College of Medicine (No. H-52092) and individual consent for this retrospective analysis was waived. We included patients with biopsy-confirmed rectal adenocarcinoma treated between 2012 and 2023 at Ben Taub Hospital and the Smith Clinic within Harris Health, a high-volume safety-net hospital system in Houston, Texas, USA, who were managed non-operatively out of necessity rather than according to a watch-and-wait guideline. Patients received either long-course chemoradiotherapy (LCRT) or short-course radiotherapy (SCRT) with chemotherapy. Systemic therapy regimens, sequencing (concurrent, induction, or consolidation), and surveillance schedules were determined by the treating multidisciplinary team based on clinical and social factors. Patients were required to have at least one post-treatment computed tomography (CT) scan performed a minimum of 10 weeks after completion of therapy; those without post-treatment imaging or follow-up were excluded.
Clinical data were extracted from electronic medical records by trained personnel and included demographic, clinical, treatment-related, and adverse event variables. Treatment-related toxicities were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. As this was not a dedicated W&W cohort, surveillance was non-protocolized and complete triple-modality restaging [digital rectal exam (DRE), endoscopy, and magnetic resonance imaging (MRI)] was available in only a minority of patients. When data were available, response was graded as follows: cCR as no visible lesion on endoscopy other than a flat scar, telangiectasia, or mucosal whitening, with no palpable abnormality on DRE and only dark fibrotic T2 signal without restricted diffusion on MRI; near-cCR as minor residual findings (superficial smooth-edged ulcer, mild mucosal irregularity, or residual intermediate T2 signal with equivocal diffusion restriction); and incomplete response as macroscopic residual tumor. Response classifications were based on contemporaneous clinical and radiographic interpretations documented in the medical record and were not reinterpreted with modern response grading criteria. LC was primarily defined as no radiographic evidence of recurrent disease on surveillance imaging. Endoscopic evaluation and pathologic confirmation were incorporated when available. A local failure (LF) following treatment was defined as local tumor regrowth after an initial response or stable disease, regardless of whether a cCR had been previously achieved. Study outcomes included LF, progression-free survival (PFS), and overall survival (OS). Survival outcomes were estimated using the Kaplan-Meier method, and LF between SCRT and LCRT was compared using the log-rank test; given the small SCRT subgroup (n=12), this comparison is exploratory. For pattern-of-failure analysis, patients with confirmed or suspected metastatic disease prior to chemoradiotherapy were excluded to focus on de novo recurrence. Ostomy-free survival (OFS) was evaluated among patients without a pre-existing ostomy, with an event defined as either death or ostomy placement, whichever occurred first; time to event was calculated from the date of diagnosis.
A total of 49 patients were identified with a median follow-up of 25 months (range, 8–90 months) (Table 1). Twelve patients (24%) were lost to follow-up before the end of the 2-year follow-up period. The cohort was 55% male and racially/ethnically diverse (63% Hispanic, 20% White, and 12% Black). The median age at diagnosis was 57 years (range, 23–85), and most patients (82%) had American Joint Committee on Cancer (AJCC) stage III or higher disease. One patient had a history of inflammatory bowel disease (IBD). Most patients (69%) were uninsured and treated under a county-based financial assistance program; 12% had Medicare, 12% had exchange-based insurance, and 6% had employer-sponsored insurance. Reasons for non-operative management included patient preference (n=24, 49%), confirmed or suspected low-burden metastatic disease or non-regional lymph node involvement (n=17, 35%), and medical comorbidities (n=8, 16%) (Figure 1). The majority (76%) received LCRT [50–55 Gy at 1.8–2 Gy/fraction (fx)] with concurrent capecitabine; the remainder received SCRT (25 Gy in 5 fx). For the patients with available data on chemotherapy (n=40), 30 (75%) underwent upfront chemotherapy prior to RT, and 10 (25%) received chemotherapy post RT. Chemotherapy regimens were heterogeneous and most included fluoropyrimidine- and oxaliplatin-based combinations such as FOLFOX (leucovorin, fluorouracil, and oxaliplatin), CAPOX/XELOX (capecitabine and oxaliplatin), and capecitabine, with some patients receiving FOLFOXIRI (leucovorin, fluorouracil, oxaliplatin, and irinotecan) or FOLFIRI (leucovorin, fluorouracil, and irinotecan). All patients underwent post-treatment CT imaging.
Table 1
| Characteristic | Value (n=49) |
|---|---|
| Age at diagnosis, years | 57 [23–85] |
| Sex | |
| Male | 27 [55] |
| Female | 22 [45] |
| Race/ethnicity | |
| Black | 6 [12] |
| White | 10 [20] |
| Hispanic | 31 [63] |
| Other | 2 [4] |
| AJCC stage | |
| I–II | 9 [18] |
| III or higher | 40 [82] |
| TNM stage | |
| T1 | 0 |
| T2 | 4 [8] |
| T3 | 23 [47] |
| T4 | 22 [45] |
| N0 | 9 [18] |
| N1 | 23 [47] |
| N2 | 17 [35] |
| M0 | 33 [67] |
| M1 | 16 [33] |
| History of IBD | 1 [2] |
| Insurance coverage | |
| Medicare | 6 [12] |
| Uninsured | 34 [69] |
| Exchange-based plan | 6 [12] |
| Employer-sponsored plan | 3 [6] |
| Radiotherapy regimen | |
| SCRT† | 12 [24] |
| LCRT | 37 [76] |
| LCRT dose, Gy | 50.4 [50–55] |
| Follow-up, months | 25 [8–90] |
Data are presented as median [interquartile range] or n [%]. †, SCRT: 25 Gy/5 fractions. AJCC, American Joint Committee on Cancer; Gy, gray; IBD, inflammatory bowel disease; LCRT, long-course radiotherapy; SCRT, short-course radiotherapy; TNM, tumor-node-metastasis.
At two years, LC, PFS, and OS were 59%, 43%, and 67%, respectively (Figure 2). LF did not differ significantly between SCRT and LCRT (P=0.51). Eighteen patients (37%) achieved an initial complete or near-cCR; among these responders, 5 subsequently developed local recurrence. Of these 18 patients, 11 underwent assessment with DRE, endoscopy, and MRI, 6 underwent CT-only assessment, and 1 underwent CT plus MRI. Among this group, one underwent salvage surgery (low anterior resection). Among patients who did not achieve cCR or near-cCR and experienced local progression, one underwent a salvage surgery (abdominoperineal resection with en-bloc posterior prostatectomy and pedicled omental flap to the pelvis) and in one patient a radical surgery was attempted but subsequently aborted due to disease extent. Twelve patients who did not achieve cCR or near-cCR maintained LC with definitive chemoradiation alone at last follow-up. Of the 4 patients with an initial near-complete response specifically, 1 (25%) experienced local progression. Ten patients (20%) had no evidence of disease at last follow-up. Five patients (10%) required an ostomy after definitive RT; median OFS was 23 months (interquartile range, 11–35 months) for patients who did not require upfront diversion. Grade ≥3 treatment-related adverse events were uncommon, occurring in four patients (8%): fistula formation (n=2), rectal stricture (n=2), and gluteal abscess (n=1); one patient experienced two events. No grade 5 events were observed.
Sixteen patients with confirmed or suspected metastatic disease prior to RT were excluded from the patterns-of-failure analysis. Among the remaining 33 patients, 17 (52%) did not experience disease progression and 21 (64%) were alive at last follow-up. Among patients who progressed (n=16), the most common pattern at first recurrence was distant-only disease (n=9, 56%), followed by simultaneous local, regional, and distant recurrence (n=4, 25%), combined local and regional recurrence (n=2, 13%), and isolated local recurrence (n=1, 6%). The most common sites of distant metastasis were lung (n=8), liver (n=5), and non-regional lymph nodes (n=3).
To our knowledge, this is among the first studies to characterize oncologic outcomes following non-operative management of LARC in a predominantly uninsured, racially and ethnically diverse safety-net population. Radiation-based therapy achieved meaningful LC with minimal serious adverse events, and 2-year LC and OS were 59% and 67%, respectively. LF did not differ significantly between SCRT and LCRT. However, the small number of patients treated with SCRT and the limited sample size restrict the ability to draw definitive conclusions regarding comparative efficacy between treatment approaches.
Our findings should be interpreted cautiously and are not directly comparable to prospective W&W trials. The OPRA trial demonstrated that W&W after TNT can preserve organs in approximately half of patients, with local regrowth in 36% overall (range, 29–44% by treatment sequence) (7). Recent real-world studies have similarly demonstrated that non-operative management can be feasible outside highly selected clinical trial populations (13). However, OPRA enrolled highly selected patients who achieved cCR or near-cCR and could adhere to rigorous surveillance. In contrast, our cohort included patients with substantial comorbidities, metastatic disease, socioeconomic barriers, and heterogeneous treatment approaches, many of whom would not have met eligibility criteria for prospective studies. Despite these challenges, a subset of patients achieved durable disease control without surgery. Approximately 37% of our patients achieved an initial complete or near-cCR, and some maintained long-term local disease control. While direct comparison is limited by differences in patient selection and surveillance intensity, these findings suggest that non-operative management may be achievable in higher-risk patients not traditionally considered for W&W.
The role of SCRT in rectal cancer treatment paradigms remains nuanced. In RAPIDO, SCRT-based therapy yielded higher pathologic complete response rates and reduced three-year disease-related treatment failure compared with LCRT followed by TME, though longer-term follow-up has raised concerns regarding higher locoregional recurrence with SCRT-based therapy (14). Chin et al. similarly reported favorable outcomes among patients achieving cCR after SCRT with consolidative chemotherapy (15). The shorter treatment duration of SCRT may also improve adherence and reduce treatment delays, which is particularly relevant in underserved populations (16). In our cohort, distant progression remained the predominant pattern of failure, suggesting that outcomes were driven primarily by systemic disease biology and real-world patient factors rather than uncontrolled local disease. Isolated local recurrence was uncommon, supporting the ability of radiotherapy to provide meaningful pelvic control in this higher-risk safety-net population.
Our study also highlights challenges in implementing W&W in underserved populations. Surveillance in our cohort was heterogeneous: while nearly all patients underwent post-treatment CT imaging, fewer than half underwent MRI or endoscopy. These gaps reflect structural barriers, given limited access to specialty care, financial constraints, transportation, and competing social priorities, all of which may delay detection of local regrowth. Prior population-based studies have reported similar variability in non-operative management and follow-up, particularly in underserved populations (12). Importantly, despite inconsistent adherence to contemporary surveillance protocols, rates of local regrowth among initial responders remained within the range reported in prospective W&W series, suggesting that clinically meaningful outcomes may still be achievable in safety-net populations facing substantial structural barriers to follow-up.
Despite these challenges, RT remains a viable non-operative treatment option for selected patients who are not surgical candidates or who decline surgery. The low rates of serious adverse events or high-grade toxicity observed in our cohort further support the safety and tolerability of this approach in a medically and socially complex population.
This study has several limitations. The retrospective design introduces potential selection bias and unmeasured confounding. The sample size is modest, and follow-up is limited, which may underreport late recurrences and toxicities. Heterogeneity in treatment regimens and surveillance practices reflects real-world care but limits direct comparison with prospective trials. In addition, the heterogeneous nature of the cohort and relatively small sample size precluded meaningful subgroup analyses. The absence of standardized response assessment criteria and protocolized surveillance further limits formal comparison of cCR rates with contemporary W&W cohorts. Finally, we acknowledge the potential for immortal time bias relating to the requirement for post-treatment imaging and follow-up to assess treatment response and outcomes.
In conclusion, in this largely pre-W&W era cohort of patients with LARC managed non-operatively out of necessity, radiation-based treatment was feasible in a safety-net setting and provided meaningful LC with an acceptable side effect profile. Notably, rates of local regrowth among responders were within the range reported in the prospective W&W series despite the substantially higher-risk nature of this cohort. Strengthening surveillance infrastructure and reducing barriers to care will be essential to optimize outcomes in underserved populations. Nonetheless, our findings suggest that non-operative management is reasonable and likely justified in patients who decline, lack access to, or are ineligible for surgery, even when strict W&W surveillance protocols cannot be implemented.
Acknowledgments
This work was presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting, September 2025.
Footnote
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0491/rc
Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0491/prf
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0491/coif). B.M. reports consulting fees from Merus and Exelixis. The other authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Ethics Board of Baylor College of Medicine (No. H-52092) and individual consent for this retrospective analysis was waived.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
References
- Saraf A, Roberts HJ, Wo JY, et al. Optimal Neoadjuvant Strategies for Locally Advanced Rectal Cancer by Risk Assessment and Tumor Location. J Natl Compr Canc Netw 2022;20:1177-84. [Crossref] [PubMed]
- Smith CA, Kachnic LA. Evolving Treatment Paradigm in the Treatment of Locally Advanced Rectal Cancer. J Natl Compr Canc Netw 2018;16:909-15. [Crossref] [PubMed]
- Li F, Zhang C, Xu L, et al. Neoadjuvant chemoradiotherapy with capecitabine based regimen in locally advanced rectal cancer: A retrospective study. Medicine (Baltimore) 2023;102:e34985. [Crossref] [PubMed]
- Turri G, Ostuzzi G, Vita G, et al. Treatment of Locally Advanced Rectal Cancer in the Era of Total Neoadjuvant Therapy: A Systematic Review and Network Meta-Analysis. JAMA Netw Open 2024;7:e2414702. [Crossref] [PubMed]
- Kalady MF, Steele SR. Top Colorectal Articles from 2021 to Inform Your Cancer Practice. Ann Surg Oncol 2023;30:5489-94. [Crossref] [PubMed]
- Oronsky B, Reid T, Larson C, et al. Locally advanced rectal cancer: The past, present, and future. Semin Oncol 2020;47:85-92. [Crossref] [PubMed]
- Verheij FS, Omer DM, Williams H, et al. Long-Term Results of Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy: The Randomized Phase II OPRA Trial. J Clin Oncol 2024;42:500-6. [Crossref] [PubMed]
- Benson AB, Venook AP, Al-Hawary MM, et al. Rectal Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2022;20:1139-67. [Crossref] [PubMed]
- Hilty Chu BK, Loria A, Dhimal T, et al. Challenges of Surveillance in Implementing Nonoperative Management for Rectal Cancer. JAMA Netw Open 2024;7:e2448682. [Crossref] [PubMed]
- Parikh AA, Robinson J, Zaydfudim VM, et al. The effect of health insurance status on the treatment and outcomes of patients with colorectal cancer. J Surg Oncol 2014;110:227-32. [Crossref] [PubMed]
- Padgett M, Kharod SM, Mercado CE, et al. Patterns-of-care disparities among uninsured versus insured patients with anorectal carcinoma referred for radiotherapy at an Urban Safety-Net Hospital. J Gastrointest Oncol 2022;13:1081-5. [Crossref] [PubMed]
- Hollis RH, Chu DI. Healthcare Disparities and Colorectal Cancer. Surg Oncol Clin N Am 2022;31:157-69. [Crossref] [PubMed]
- Encarnación JA, Ibáñez N, De la Fuente I, et al. Clinical Complete Response and Organ Preservation Strategies in Rectal Cancer: A Real-World Single-Center Experience. Cancers (Basel) 2026;18:763. [Crossref] [PubMed]
- Bahadoer RR, Dijkstra EA, van Etten B, et al. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol 2021;22:29-42. [Crossref] [PubMed]
- Chin RI, Roy A, Pedersen KS, et al. Clinical Complete Response in Patients With Rectal Adenocarcinoma Treated With Short-Course Radiation Therapy and Nonoperative Management. Int J Radiat Oncol Biol Phys 2022;112:715-25. [Crossref] [PubMed]
- Chakrabarti D, Rajan S, Akhtar N, et al. Short-course radiotherapy with consolidation chemotherapy versus conventionally fractionated long-course chemoradiotherapy for locally advanced rectal cancer: randomized clinical trial. Br J Surg 2021;108:511-20. [Crossref] [PubMed]
