Organ preservation in rectal cancer: opportunity within boundaries

Abstract

Purpose

To highlight the opportunities and pitfalls of organ-preservation strategies for rectal cancer and to define the clinical circumstances in which radical total mesorectal excision (TME) remains imperative, particularly when treatment is delivered outside referral centres.

Methods

Two illustrative patients initially managed in a tertiary hospital that is not a referral centre for rectal cancer and organ-preservation strategies are presented. Clinical records, imaging, histopathology, and follow-up were reviewed. Key management decisions were compared with current European Society for Medical Oncology (ESMO) and Italian Association of Medical Oncology (AIOM) guidelines, as well as recent evidence from systematic reviews.

Results

Case 1 involved a bulky (10 cm), circumferential cT3N + mucinous adenocarcinoma. Despite apparent local control after transanal excision, the patient developed sphincter-destructive recurrence requiring abdominoperineal resection; final pathology was ypT3N2b KRAS-mutant. Case 2 concerned an initially pT1 rectal adenocarcinoma in a 6-cm laterally spreading tumour, but surveillance was non-standardized; the patient re-presented with metastatic (liver) mucinous adenocarcinoma 4 years later, misdiagnosed as liver abscesses. In both patients, deviation from guideline criteria (tumour size, nodal status, unfavourable histology, or inadequate follow-up) led to undertreatment and delayed radical therapy.

Conclusion

Organ preservation offers functional benefits but must be confined to rigorously selected low-risk lesions within prospective protocols and high-volume centres. Radical TME remains the gold standard when guideline criteria are not fully met or staging is ambiguous.

Supplementary Information

The online version contains supplementary material available at 10.1007/s00384-025-04984-w.

Introduction

Organ preservation in carefully selected patients with rectal cancer can reduce surgical morbidity and preserve quality of life [1, 2]. Over the past decade, real‑world series reported that up to 25–30% of patients treated with neoadjuvant therapy are managed on watch‑and‑wait or organ‑preservation pathways [3, 4]. Nevertheless, such strategies should be adopted only within the framework of rigorous protocols or registries that guarantee oncological safety and high-quality standards [4–7].

In this article, we aim to illustrate two cases encountered in real-life settings, where surgeons faced complex clinical scenarios also due to previous clinical and surgical decisions taken disregarding national and international guidelines. Case 1 was chosen to illustrate how recommendations for patient selection for organ‑preservation were not adequately interpreted and applied in a hospital setting lacking sufficient expertise in organ‑preservation strategies and where advanced pelvic magnetic resonance imaging (MRI), high‑volume transanal surgery, and formal multidisciplinary review are not routine. Case 2 similarly exposes the consequences of a sub‑optimal follow‑up protocol in a patient receiving transanal endoscopic microsurgery. Both case history was reconstructed and detailed to highlight the erroneous steps in the surgical treatment and clinical management and reviewed in light of the clinical practice guidelines that should have been followed to ensure quality standards and safety of care. By presenting these two examples, the article ultimately aims to highlight the potential severe consequences of failing to adhere to clinical practice guidelines, particularly in terms of surgical outcomes and oncological safety.

The study is reported following the CAse REport (CARE) Guidelines and Checklist to ensure transparent and high-quality reporting [8].

Case 1

A 62‑year‑old woman was referred in April 2024 to our unit for a second opinion regarding a suspected recurrent rectal cancer after a local excision and mucosal pexy (the latter for a grade II rectal prolapse) performed a year earlier. The patient’s medical history included atrial fibrillation treated with anticoagulants, mitral and aortic valve replacement, and hypothyroidism. In September 2022, a colonoscopy for rectal bleeding revealed a large, circumferential rectal mass extending 10 cm from the dentate line. Biopsy showed high‑grade epithelial neoplasia consistent with adenocarcinoma arising in a tubulovillous adenoma with low‑grade dysplasia. Staging CT and pelvic MRI demonstrated a bulky, semicircumferential cT3 rectal lesion with no clear plane between the tumour and the levator ani muscles and suspicious mesorectal and presacral lymphadenopathies. After multidisciplinary discussion, the patient received long‑course chemoradiotherapy (50 Gy in 25 fractions plus capecitabine). Restaging imaging showed only minor downsizing and persistent nodal involvement. Despite these unfavourable features, the patient underwent circumferential transanal excision and mucosal pexy (for a concomitant grade II rectal prolapse already documented in 2022) in March 2023. Histopathology confirmed a moderately differentiated mucinous adenocarcinoma invading the submucosa (pT1) with a 2‑mm clear deep margin (R0). Therefore, the patient entered 6-month active surveillance with colonoscopy, pelvic MRI, and CT. At 6 months (October 2023), colonoscopy revealed a villous lesion 5 cm from the dentate line, and biopsy showed a tubulovillous adenoma with low‑grade dysplasia. CT and PET demonstrated stable nodal disease and a suspicious perineal collection.

At 1 year (second-opinion visit), clinical, endoscopic, and radiological findings suggested circumferential local recurrence with anal-sphincter involvement. A robot‑assisted abdominoperineal resection with permanent colostomy (Miles procedure) was performed in May 2024. Final pathology revealed mucinous adenocarcinoma infiltrating the perirectal fat with positive radial margins and 10 out of 13 metastatic lymph nodes (ypT3N2b). Molecular analysis showed a microsatellite‑stable tumour with a KRAS G12V mutation. The patient received six cycles of XELOX but discontinued because of toxicity. Follow‑up imaging to date (1-year follow-up) shows no disease recurrence.

Case 2

A 56‑year‑old man was referred in March 2025 to our unit after repeated hospitalizations for recurrent fever attributed to liver abscesses.

The medical history of the patient was reviewed. In March 2019, he presented to the Emergency Department with abdominal pain, altered bowel habit, intermittent constipation, narrow‑calibre stools, and rectal bleeding. Colonoscopy revealed pseudopolypoid rectal lesions with a histological diagnosis of tubular adenoma with low‑grade dysplasia. Repeat sigmoidoscopy in June 2019 identified a laterally spreading tumour (LST) occupying nearly half of the rectal lumen. Pelvic MRI showed a mucosal‑based lesion extending from 3 to 9 cm from the anal verge, two 5‑mm mesorectal lymph nodes with two morphologically suspicious characteristics (round shape and heterogeneous signal), and no extramural invasion or mesorectal fascia involvement. In July 2019, he underwent endoscopic mucosal resection, which confirmed a tubulovillous adenoma with high‑grade dysplasia. Three months later, sigmoidoscopy demonstrated a recurrent lesion with high‑grade dysplasia and intramucosal adenocarcinoma (pTis). In December 2019, transanal endoscopic microsurgery (TEM) was performed and pathology showed a moderately differentiated adenocarcinoma (pT1) within a tubulovillous adenoma, with negative margins, no lymphovascular invasion, and a 2.8-mm depth of submucosal invasion (the pathologist did not quantify the percentage of carcinoma within the adenoma, and tumour budding was not reported). Postoperative MRI and CT showed residual rectal wall thickening, interpreted as postoperative changes. Post‑TEM surveillance consisted of pelvic MRI at 6 months and colonoscopy at 1 and 4 years, while no abdominal or thoracic CT was performed during the ensuing 5 years. From April 2023, the patient experienced recurrent febrile episodes, rising inflammatory markers, and sepsis. Cross-sectional imaging (CT and PET) revealed multiple hypermetabolic liver lesions with hypermetabolic lymphadenopathy that were repeatedly drained as abscesses. Aspiration of a dominant segment VII lesion yielded 300 ml of purulent fluid positive for Escherichia coli. The patient underwent repeated hospitalizations for sepsis requiring further percutaneous drainage and antibiotics. Although the abscess resolved radiologically, hypermetabolic hepatic lesions persisted, and tumour markers (CEA, CA 19‑9) continued to rise. A liver biopsy in June 2024 showed necrotic material with chronic inflammatory infiltrate but no malignancy. At the time of our observation, the case was discussed in a multidisciplinary review (second-opinion visit), and because of recurrent sepsis, surgery was planned. At laparotomy in April 2025, the intended wedge resection of the segment VII abscess was interrupted when multiple hepatic nodules and peritoneal carcinomatosis were found. Frozen section of a segment IV lesion revealed mucinous adenocarcinoma, and hepatic resection was therefore abandoned. Final histology confirmed metastatic mucinous adenocarcinoma.

Debate

These cases highlight the complexity of rectal cancer management when organ‑preservation strategies are pursued. These vignettes do not question the value of organ preservation per se; rather, they show how ignoring established selection and surveillance recommendations can jeopardize the oncological safety of the technique.

In Case 1, the initial lesion was large (10 cm), circumferential with a cT4 growth, and close to the anal sphincter, all recognized contraindications to organ preservation [4, 6, 7]. In addition, restaging MRI after chemoradiotherapy showed persistent nodal disease. Total mesorectal excision (TME) should therefore have been recommended as first‑line treatment [5]. Given the unfavourable pathology (moderately differentiated mucinous adenocarcinoma), a salvage TME (after TEM) rather than surveillance would also have been reasonable. This case underscores the limitations of organ-preservation strategies for large, circumferential rectal cancers situated near the anal sphincter. Incomplete disease eradication after local excision, altered anatomical landmarks created by the transanal rectopexy, and adverse tumour biology (including mucinous histology, nodal positivity, and a KRAS mutation) collectively heightened the risk of recurrence.

In Case 2, preoperative MRI showed suspicious lymph nodes and a large (6 cm) lesion, yet an organ‑preservation approach was chosen. The diagnostic limitations of MRI for nodes ≤ 5 mm and the potential for reactive hyperplasia to mimic metastasis should be acknowledged [9, 10]. Nevertheless, the 2016 European Society of Gastrointestinal and Abdominal Radiology (ESGAR) stated the following criteria for malignant node [11]: (1) short axis diameter ≥ 9 mm; (2) short axis diameter 5–8 mm and more than 2 morphologically suspicious characteristics (round shape/irregular border/heterogeneous signal); (3) short axis diameter < 5 mm and 3 morphologically suspicious characteristics (round shape/irregular border/heterogeneous signal); and (4) all mucinous lymph node regardless of size. That standard would already have classified both Case 1 and Case 2 as cN +, tipping management towards radical TME. Equally stringent are the post-local excision or TEM surveillance schedules. The European Society of Gastrointestinal Endoscopy (ESGE) advocates a colonoscopy at 1, 3, and 5 years [12]. In contrast, the American Gastroenterology Association (AGA) and the National Comprehensive Cancer Network (NCCN) clinical practice guidelines advise flexible sigmoidoscopy coupled with pelvic MRI or endoscopic ultrasound every 3–6 months up to 5 years, and also consider CT for 3–5 years [13, 14]. Case 2 deviated from every one of these timelines: a pelvic MRI was carried out at 6 months, colonoscopy at 1 and 4 years, whereas no abdominal CT was performed for 5 consecutive years, allowing hepatic metastases to present as ‘abscesses’. In addition, postoperative MRI and CT revealed residual wall thickening and nodal disease that were not adequately investigated and followed up. This sequence delayed the identification of systemic disease and definitive management.

These cases underscore the need for meticulous patient selection for organ preservation in rectal cancer surgery.

Recent data further sharpen these observations. A recent systematic review and meta‑analysis by Tan et al. (18 studies, 1907 patients) offers a most granular comparison between watch-and-wait, local excision, and radical surgery [15]. Pooled data showed no significant difference in overall survival (HR, 0.92; 95% CI, 0.52–1.64; p = 0.777) or 5‑year disease‑free survival when watch-and-wait was compared with either local excision or radical surgery. Importantly, local recurrence behaved very differently according to the surgical comparator: watch-and-wait and local excision were oncologically equivalent (RR, 1.11; 95% CI, 0.61–2.05; p = 0.727), whereas watch-and-wait more than doubled local failure versus radical surgery (RR, 2.91; 95% CI, 1.79–4.73; p < 0.001). Rates of distant metastasis and overall mortality likewise did not differ significantly among groups, but watch-and-wait reduced permanent‑stoma formation by 65% (RR, 0.35; 95% CI, 0.20–0.61; p < 0.001) compared with surgical treatment.

Fleming et al. reported a multi‑institutional series of 152 cT4 rectal cancers treated on a tumour response‑adapted spectrum (from organ preservation to pelvic exenteration) after neoadjuvant treatment. Although 3‑year overall and distant‑metastasis‑free survival were comparable across the different strategies, organ preservation carried a 30.2% local regrowth rate versus 5.4% after standard TME and only 2% after abdominal perineal resection or pelvic exenteration [16]. These figures mirror the sphincter-destructive recurrence seen in Case 1 and emphasize that even after substantial down-staging, cT4 or circumferential tumours require lifelong, protocol-driven surveillance or, when in doubt, radical resection [16].

In a controlled cohort of 40 watch-and-wait versus 40 matched TME patients, Ferri et al. confirmed that watch-and-wait yields equivalent 3‑year metastasis‑free and overall survivals; however, watch-and-wait incurred a 22% early local regrowth and a nearly 50% permanent stoma rate after salvage surgery (versus 20% in the TME group). Cost‑effectiveness favoured watch-and-wait for low tumours, yet complex salvage procedures partly eroded the functional dividend [17]. This underlines the central lesson from both of our cases: stretching selection criteria or relaxing follow‑up protocols quickly tilts the risk–benefit balance toward undertreatment and delayed radical therapy.

Process‑mining analysis of 453 Italian patients treated between 2017 and 2021 showed that a moderate proportion deviated from the European Society for Medical Oncology (ESMO) rectal‑cancer pathways, chiefly because radiotherapy was intensified or oxaliplatin was added to the chemotherapy regimen [18]. Our cases revealed two deviations: Case 1 illustrates undertreatment after an incomplete response with nodal disease, whereas Case 2 highlights inadequate follow‑up and undertreatment of nodal disease. Consequently, the principles articulated in international (ESMO) [5] and national (Associazione Italiana di Oncologia Medica, AIOM) [19] guidelines, such as strict size cutoffs (≤ 3–4 cm), absence of adverse histology, and reliable exclusion of nodal disease, remain indispensable checkpoints before opting for local excision. Similar features were also explicitly considered inclusion criteria in three RCTs: the ACOSOG Z6041 trial included T2N0 rectal cancer with a diameter ≤ 4 cm and involving ≤ 40% of the rectum circumference [7], the GRECCAR-2 trial included T2-3N0-1 rectal cancer ≤ 4 cm and residual tumour ≤ 2 cm after neoadjuvant chemoradiotherapy [4], and the TREC trial included T1-2N0 rectal adenocarcinoma with a diameter ≤ 3 cm [6]. Although such an approach preserves sphincter function and avoids major surgery, it precludes nodal assessment and accurate staging. Local excision should therefore be reserved for strictly low‑risk lesions in which nodal metastasis can be reliably excluded. In ambiguous cases, radical resection with TME remains the gold standard for accurate staging and cure [20–22].

The TAUTEM randomized controlled trial, published in 2025, tried to benchmark a modern organ‑preservation protocol alternative to TME [23]. This prospective, multicenter (17 Spanish centres), open-label, noninferiority, phase 3 study enrolled 173 patients with cT2–T3ab N0 M0 rectal adenocarcinoma located at ≤ 4 cm and ≤ 10 cm from the anal verge. After long‑course chemoradiotherapy, patients were randomized to either TME or TEM. The protocol for follow-up in the first 2 years involved rectoscopy and tumour markers every 4 months, and subsequently, annual colonoscopy, MRI, and CT scans of the abdomen, pelvis, and thorax for 5 years. At 5 years, locoregional recurrence was 7.4% in the CRT‑TEM arm versus 6.2% after TME, comfortably within the pre‑specified 10% non‑inferiority margin. Distant recurrence (12.3% vs 17.3%), overall survival (82.7% vs 85.2%), and disease‑free survival (88.9% in both arms) were likewise comparable. Crucially, CRT‑TEM yielded a 77.8% permanent organ‑preservation rate and halved postoperative morbidity (21% vs 51%). Almost half the CRT‑TEM cohort achieved a pathologic complete response (44.3%), none of whom developed local or distant relapse. The TAUTEM trial, therefore, confirms that CRT–TEM achieved noninferior local‑recurrence control to standard TME for stage T2–T3ab, N0, M0 disease, with similarly favourable outcomes for distant relapse, overall and disease‑free survival, and maintenance of clear circumferential margins.

Both cases reported here would have been excluded from TAUTEM for nodal disease and diameter > 4 cm, emphasizing how easily guidelines are overridden in everyday settings. In summary, organ preservation must operate within narrow, evidence‑based confines and under vigilant surveillance. When those guardrails are ignored, the functional gains are swiftly erased by avoidable oncologic failure. Surgical decision‑making must balance the risks of overtreatment (TME) against undertreatment (TEM), integrating clinical, histopathological, and imaging data with patient preferences. When uncertainty persists about nodal status, especially in young and fit patients, radical surgery should be favoured to minimize the risk of recurrence. Oncological safety can be ensured only through surgical expertise, stringent patient selection, and systematic outcome monitoring.

Conclusion

Organ‑preservation strategies for rectal cancer should be offered at high‑volume centres for tumours that meet all oncological safety criteria, and within strict clinical and surveillance protocols. Radical TME remains mandatory whenever criteria are violated or reliable follow‑up cannot be guaranteed. Only within these boundaries may organ preservation be realized without compromising oncological outcomes.

Supplementary Information

Below is the link to the electronic supplementary material.

Author contribution

All authors made substantial contributions to the conception of the work, the acquisition, analysis, interpretation of data, drafted the work and revised it critically for important intellectual content, approved the version to be published and agree to be accountable for all aspects of the work in ensuring that questions to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Competing interests

The authors declare no competing interests.