Organ Preservation In Rectal Cancer Research Articles

Local excision to enhance organ preservation in rectal cancer after favorable response to total neoadjuvant therapy.

84 Background: Total neoadjuvant therapy (TNT) for rectal cancer (RC) can achieve clinical complete response (cCR) and organ preservation in as many as 45% of patients, with watch-and-wait (WW) management. For tumors that persist or regrow after TNT, standard management is total mesorectal excision (TME), which can result in poor bowel function or permanent colostomy. In certain cases, only residual adenoma or mucosal based carcinoma may remain after TNT. Local excision (LE) is a minimally invasive surgical alternative that preserves the rectum. Here we evaluate case selection, safety, and efficacy of LE for small tumors that persist or regrow after TNT. Methods: Our retrospective review identified 72 RC patients from August 2010 – July 2023 who underwent LE for tumors that either remained after TNT or achieved cCR and later regrew. Median follow up from end of TNT was 3.2 years. LE was selectively offered if the tumor was suspected to arise from an adenoma or a small cancer confined to mucosa, based on clinical impression and biopsy. Collected data included tumor characteristics and pathology, surgical complications, length of stay (LOS), local and distant tumor recurrence, and organ preservation. Results: Pretreatment MRI staging was 5% T1, 23% T2, 68% T3, and 4% T4. Median distance from anal verge was 4.8 cm. 90-day complications after LE included dehiscence (6%), rectal pain (5%), transient urinary retention (4%), bleeding (4%), and minor incontinence (4%). One patient developed pelvic sepsis requiring drainage of perirectal abscess and fecal diversion. Median LOS was 1 day (range 0-4). Pathologic review demonstrated invasive cancer in 27 LE specimens, while 45 had either benign pathology or carcinoma in situ (table 1). R1 pathology was present in 8 of 27 (30%) invasive cancer specimens. 6 of 27 (22%) patients with invasive cancer (3 ypT1, 3 ypT2) subsequently underwent TME. 3 of 27 patients (11%) developed distant metastases. Of the 45 patients with benign LE pathology, 3 (7%) later required TME for subsequent cancer regrowth (range 4-22 months after LE). 4 of 45 patients (8%) developed distant metastases. Overall organ preservation rate following LE was 87.5%, with median follow-up of 2.4 years after surgery. For all 9 LE patients who ultimately underwent TME, there were no pelvic recurrences and one distant recurrence. Conclusions: Small, mucosal based tumors that contain minimal or no invasive cancer are common findings after TNT. For appropriately selected patients, LE is a safe and effective initial option, given high observed rates of local control and organ preservation, with low surgical morbidity. If more advanced disease is encountered on final pathology, TME should be considered. These data support the use of LE as an important adjunct to WW management. [Table: see text]

Organ-preservation in rectal cancer: What is at risk when offering watch and wait for a clinical complete response? Data from 2 international registries in rectal cancer.

7 Background: Organ-preservation has become an attractive alternative to total mesorectal excision (TME) among patients with rectal cancer following neoadjuvant therapy. Patients who achieve a clinical complete response (cCR) are currently offered watch-and-wait (WW) without immediate resection. Nearly 30% of these patients will develop local regrowth usually within 3 years from initial decision to WW. While salvage resection is frequently feasible, keeping the primary tumor in situ (despite clinically undetectable) may contribute to the risk for development of subsequent distant metastases (DM). The aim of the present study is to compare the risk of DM between patients with local regrowth (LR) after WW (undetectable residual disease) and patients with near-complete pathological response managed by TME at time of reassessment of response. Methods: Data from patients with rectal cancer following neoadjuvant therapy entered a prospective international database (IWWD) with cCR managed by WW and subsequent LR were compared to patients managed by TME from a prospectively maintained national registry (VIKINGO project). Near-complete response was defined at the presence of ≤10% residual cancer cells in the resected specimen. Primary endpoint was DM-free survival at 3 years from decision to WW or TME. Cox-logistic regression was performed to search for predictors of DM development. Kaplan-Meier curves were used to compare DM-free survival between groups based on statistically significant features found at multivariate analysis (p≤0.05) using log-rank test. Results: 508 patients with LR were compared to 893 patients with near-complete response after TME. Overall, DM rate was significantly higher among local regrowths (22.8% vs. 10.2%,; p≤0.001). Independent risk factors for DM included LR (versus TME at reassessment; p=0.001), ypT3-4 status (p=0.016) and ypN+ status (p=0.001) at the time of surgery. 3yr-DM-free survival was significantly worse for patients with local regrowth (75% vs. 87%; p=0.001). When stratified for pathological stage, patients with local regrowth did significantly worse through all stages ypT1-2N0 (p<0.001); ypT3-4N0 (p=0.009) and ypTanyN+ (p<0.001). Conclusions: Development of LR following WW is a significant and independent risk factor for subsequent DM. Final pathological stage is also a risk factor for subsequent DM. Patients with local regrowth have a higher risk for subsequent DM development than patients managed by TME at restaging irrespective of final ypT and ypN status. Leaving the primary undetectable tumor in situ until development of local regrowth may result in worse oncological outcomes. Future studies incorporating organ-preservation strategies should focus on the subsequent risk of DM among patients who eventually develop local regrowth as one of clinically relevant primary endpoints.

Sense and non-sense of imaging in the era of organ preservation for rectal cancer.

This review summarizes the current applications and benefits of imaging modalities for organ preservation in the treatment of rectal cancer. The concept of organ preservation in the treatment of rectal cancer has revolutionized the way rectal cancer is managed. Initially, organ preservation was limited to patients with locally advanced rectal cancer who needed neoadjuvant therapy to reduce tumor size before surgery and achieved complete response. However, neoadjuvant therapy is now increasingly utilized for smaller and less aggressive tumors to achieve primary organ preservation. Additionally, more intensive neoadjuvant strategies are employed to improve complete response rates and increase the chances of successful organ preservation. The selection of patients for organ preservation is a critical component of treatment, and imaging techniques such as digital rectal exam, endoscopy, and MRI are commonly used for this purpose. In this review, we provide an overview of what imaging modalities should be chosen and how they can aid in the selection and follow-up of patients undergoing organ-preserving strategies.

OC-0458 Contact x-ray radiotherapy (Papillon) for organ preservation in rectal cancer

OC-0458 Contact x-ray radiotherapy (Papillon) for organ preservation in rectal cancer

OC-0272 Organ preservation in rectal cancer: the randomised STAR-TREC phase II trial

OC-0272 Organ preservation in rectal cancer: the randomised STAR-TREC phase II trial

Prevalent Pseudoprogression and Pseudoresidue in Patients With Rectal Cancer Treated With Neoadjuvant Immune Checkpoint Inhibitors.

Immune checkpoint inhibitor (ICI) treatment in patients with microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) tumors holds promise in reshaping organ preservation in rectal cancer. However, the benefits are accompanied by distinctive patterns of response, introducing a dilemma in the response evaluation for clinical decision-making. Patients with locally advanced rectal cancer with MSI-H/dMMR tumors receiving neoadjuvant ICI (nICI) treatment (n=13) and matched patients receiving neoadjuvant chemoradiotherapy (nCRT; n=13) were included to compare clinical response and histopathologic features. Among the 13 patients receiving nICI treatment, in the final radiologic evaluation prior to surgery (at a median of 103 days after initiation of therapy), progressive disease (n=3), stable disease (n=1), partial response (n=7), and complete response (n=2) were observed. However, these patients were later confirmed as having pathologic complete response, resulting in pseudoprogression and pseudoresidue with incidences of 23.1% (n=3) and 76.9% (n=10), respectively, whereas no pseudoprogression was found in the 13 patients receiving nCRT. We further revealed the histopathologic basis underlying the pseudoprogression and pseudoresidue by discovering the distinctive immune-related regression features after nICI treatment, including fibrogenesis, dense lymphocytes, and plasma cell infiltration. Pseudoprogression and pseudoresidue were unique and prevalent response patterns in MSI-H/dMMR rectal cancer after nICI treatment. Our findings highlight the importance of developing specific strategies for response evaluation in neoadjuvant immunotherapy to identify patients with a good response in whom sphincter/organ-preserving or watch-and-wait strategies may be considered.

Organ preservation in rectal cancer with short-course radiotherapy and a papillon boost: An international multicentre analysis

Category: Outcomes of treatment (including chemotherapy, chemo-RT and RT)

Reduction of Tumor Length by >50%, Post Neoadjuvant Chemoradiation as a Predictor for Complete Response and Organ Preservation in Rectal Cancer

<h3>Purpose/Objective(s)</h3> 20-30% of the locally advanced rectal cancer patients undergoing neoadjuvant chemoradiation (NACRT) have complete response (CR) and are suitable for wait and watch approach. This tumor response can be enhanced by radiotherapy dose escalation such as brachytherapy which is typically given at the end of NACRT. However, there is no data so as to which patients are likely to benefit by brachytherapy to achieve CR. We aimed to identify decrease in tumor length following CTRT, as predictor of CR, and eventual organ preservation. <h3>Materials/Methods</h3> Patients diagnosed with T2-T4, N0-N2 distal rectal cancer treated from December 2017 to March 2021 were retrospectively reviewed. All were treated with radiation dose of 50 Gray (Gy) in 25 fractions (#) with concurrent capecitabine. All patients received escalated dose of radiation by high dose rate endorectal brachytherapy of 8-12 Gy in 2-3 #s within 2 to 3 weeks post CTRT. Baseline tumor length (MRI) and residual tumor length after CTRT during brachytherapy (assessed with planning MRI) were compared for response. Statistical analysis was done to determine decrease in tumor length as predictor of CR. <h3>Results</h3> One hundred patients records were reviewed. Disease and treatment characteristics are provided in table 1. Median length of tumor at baseline was 4.9 cm (3.8-6 cm). 39 patients had >50% decrement in tumor length (median length 3 cm) from baseline post CTRT, whereas 61 patients had <50% response. Out of 39 patients with>50% response, 26 patients achieved CR (66.7%) while 13 patients had partial or no response (33.3%), while out of 61 patients with <50% decrease in tumor length, 27 achieved CR (44.2%) and 34 had partial or no response (55.8%). The patients who had >50% reduction in tumor length had higher probability of achieving CR than the patients with <50% reduction (66% vs 44% p=0.029). <h3>Conclusion</h3> Response assessment at the end of CTRT with respect to decrease in length of tumor may predict CR and thus can lead to better selection of patients for escalated radiation dose via endorectal brachytherapy leading to higher rate of organ preservation.

Online MR guided dose escalated radiotherapy for organ preservation in distal rectal cancer

IntroductionNon-surgical management of rectal cancer aiming for organ-preservation is an important development to improve rectal cancer treatment. Dose escalated radiotherapy represents one approach to increase clinical complete response (cCR) rates. In the present study we present feasibility and outcome data on rectal cancer patients who were treated with dose escalated radiotherapy using an MR guided online response-adaptive workflow. Material and methodsA total of five patients were treated with 45 Gy in 25 fractions to the mesorectum and the internal iliac lymph nodes and a simultaneous integrated boost to the primary tumor with 50 Gy in 25 fractions on a conventional linac. In addition, weekly response-adaptive boost fractions with 3 Gy per fraction were scheduled on a 1.5 T MR-Linac. Concomitant chemotherapy with 5-fluorouracil was given as continuous venous infusion during the first and last week of treatment. Response was evaluated approximately-three months after the end of treatment and surgery was omitted in case of a clinical complete response (cCR) or a near cCR. Toxicity was graded by using PRO-CTCAE, Quality of life by the EORTC-QLQ-C30 questionnaire and continence according to the Wexner scale. ResultsResponse-adaptive dose escalated radiotherapy was feasible and well tolerated by all patients. Four reached a clinical complete response, one had a local excision confirming pathological complete response (pCR). All PRO-CTCAE grade 3 toxicities resolved within six months after the end of treatment. Quality of life and continence scores during follow-up were comparable to baseline levels. ConclusionDose-escalated online response-adaptive MR-guided radiotherapy appears to be a very promising treatment with the goal of organ preservation in rectal cancer leading to high response rates, excellent organ function and limited side effects. Further prospective evaluation is needed.

Organ Preservation in Rectal Cancer: An Overview of the Dutch Perspective and Recent Developments

Although current guidelines on rectal cancer treatment often recommend rectal resection with or without neoadjuvant (chemo)radiotherapy, there is growing interest in organ-preserving treatment approaches among patients and clinicians in the Netherlands. Currently, multiple ongoing studies are investigating the value of different non-operative treatment modalities to improve tumour response rates and increase the chance of successful organ preservation. Papillon contact X-ray brachytherapy is a promising treatment modality to improve the chance of organ preservation, which seems especially relevant for elderly and frail patients unable or refusing to undergo total mesorectal excision surgery. The elderly and frail patient with rectal cancer poses a significant challenge and warrants a thorough multidisciplinary approach to provide the most optimal organ-preserving treatment. In this overview, an insight into the Dutch perspectives and developments within the field of organ preservation and the set-up of a Papillon facility to complete the spectrum of organ-preserving treatment options in a tertiary referral centre for rectal cancer treatment has been provided.

Organ preservation in rectal cancer: review of contemporary management.

Organ preservation as a successful management for rectal cancer is an evolving field. Refinement of neoadjuvant therapies and extended interval to response assessment has improved tumour downstaging and cCR rates. This was a narrative review of the current evidence for all aspects of organ preservation in rectal cancer management, together with a review of the future direction of this field. Patients can be selected for organ preservation opportunistically, based on an unexpectedly good tumour response, or selectively, based on baseline tumour characteristics that predict organ preservation as a viable treatment strategy. Escalation in oncological therapy and increasing the time interval from completion of neaodjuvant therapy to tumour assessment may further increase tumour downstaging and complete response rates. The addition of local excision to oncological therapy can further improve organ preservation rates. Cancer outcomes in organ preservation are comparable to those of total mesorectal excision, with low regrowth rates reported in patients who achieve a complete response to neoadjuvant therapy. Successful organ preservation aims to achieve non-inferior oncological outcomes together with improved functionality and survivorship. Future research should establish consensus of follow-up protocols, and define criteria for oncological and functional success to facilitate patient-centred decision-making. Modern neoadjuvant therapy for rectal cancer and increasing the interval to tumour response increases the number of patients who can be managed successfully with organ preservation in rectal cancer, both as an opportunistic event and as a planned treatment strategy.

OC-0833 Total neoadjuvant therapy for Organ Preservation in Rectal Cancer: The CAO/ARO/AIO-16 phase II trial

OC-0833 Total neoadjuvant therapy for Organ Preservation in Rectal Cancer: The CAO/ARO/AIO-16 phase II trial

OC-0622 Propensity- Score analysis of Proctectomy-TME vs Organ Preservation for Rectal cancer

OC-0622 Propensity- Score analysis of Proctectomy-TME vs Organ Preservation for Rectal cancer

Organ preservation in rectal cancer: towards the norm rather than the exception.

Organ preservation is a hot topic in rectal cancer management. With the increasing number of trials now reporting success with organ preservation in early and locally advanced rectal cancer, this short review considers how organ preservation will continue to integrate into clinical practice and what this will mean for rectal cancer surgeons.

Neoadjuvant Capecitabine and Oxaliplatin Before Concurrent Capecitabine and Radiation in Locally Advanced Rectal Cancers: Experience of a Cancer Hospital in Pakistan.

PURPOSETo report the toxicity and pathologic response rates after adding neoadjuvant capecitabine and oxaliplatin (CAPOX) followed by concurrent radiation and capecitabine (CAPRT) and surgery in patients with locally advanced rectal cancer.MATERIALS AND METHODSWe retrospectively analyzed medical records of 301 patients between January 2007 and December 2014. Patients were treated with four cycles of neoadjuvant chemotherapy comprising CAPOX, followed by radiotherapy at doses of 45-54 Gy in 25-30 fractions with concurrent capecitabine. A response assessment scan was performed at 4-6 weeks postradiation followed by surgical evaluation at 6-8 weeks. Pathologic tumor and nodal response rates as well as circumferential resection margin were assessed on surgical specimens.RESULTSThe median age of the patients was 43 years (range, 16-78). Overall, 227 (75.4%) patients were able to complete four cycles of CAPOX. Neoadjuvant chemotherapy was well-tolerated with no serious adverse effects. The most common toxicity was diarrhea (grade 2, n = 108; 35.8%; grade 3, n = 57; 18.9%; grade 4, n = 25; 8.3%) followed by neuropathy (grade 2, n = 132; 43.8%; grade 3, n = 54; 17.9%) and oral mucositis (grade 2, n = 108; 35.8%; grade 3, n = 47; 15.6%; grade 4, n = 9; 2.99%). A total of 229 (76.1%) patients underwent surgery. Pathologic complete response was seen in 52 (22.7%; 95% CI, 13 to 28), whereas 200 (87.3%; 95% CI, 82 to 99) patients had a negative circumferential resection margin on pathology.CONCLUSIONNeoadjuvant chemotherapy with CAPOX before CAPRT and planned total mesorectal excision surgery result in good tumor regression and substantial pathologic complete response rates with acceptable toxicity. With growing interest in organ preservation in rectal cancer, the strategy of completing all chemotherapy and chemoradiotherapy before planned surgery offers a favorable paradigm. However, further randomized clinical trials are needed to support this evidence.

Moving forward with organ preservation in rectal cancer

The concept of radical cancer surgery is about 150 years old and was developed at a time when patients presented with large tumours and surgery was the only treatment option available. The belief that the more extensive the operation, the greater the chance for cure peaked at the end of the first half of the 20th century. Gradually, however, surgeons tried to maintain the same oncological outcomes with less mutilating resections, often combining surgery and radiotherapy, and sometimes even with radiotherapy as the primary approach and surgery as the backup plan.

Mass spectrometry transanal minimally invasive surgery (MS-TAMIS) to promote organ preservation in rectal cancer

BackgroundTransanal minimally invasive surgery (TAMIS) is deployed for organ preservation in early rectal cancer and significant rectal polyps. Rapid evaporative ionisation mass spectrometry (REIMS) provides biochemical tissue analysis, which could be applied intraoperatively to give real-time tissue feedback to the surgeon and decrease the risk of an involved margin. However, the accuracy and feasibility of this approach have not been established.MethodsIn this prospective observational study, patients undergoing resection of rectal adenomas or carcinomas were recruited. An electrosurgical handpiece analysed tissues ex vivo using diathermy, with the aerosol aspirated into a Xevo G2-S ToF mass spectrometer. The relative abundance of lipids underwent predictive statistical modelling and leave-one-patient-out cross-validation. The outcomes of interest were the ability of REIMS to differentiate normal, adenomatous and cancerous tissue, or any disease subtype from normal. REIMS was coupled with TAMIS for in vivo sampling, assessing the accuracy of tissue recognition and distinguishing bowel wall layers.ResultsForty-seven patients were included, yielding 266 spectra (121 normal, 109 tumour and 36 adenoma). REIMS differentiates normal, adenomatous and cancerous rectal tissues with 86.8% accuracy, and normal and adenomatous tissue with 92.4% accuracy and 91.4% accuracy when differentiating disease from normal. We have performed the first five in-man mass spectrometry augmented TAMIS (MS-TAMIS). In real time, MS-TAMIS can differentiate rectal mucosa and submucosa based on their relative abundance of triglycerides and glycerophospholipids. The ex vivo accuracy distinguishing diseased and normal tissues is maintained in vivo at 90%, with negative predictive value of 95%. The system identified a deep and lateral involved tumour margin during TAMIS.ConclusionsREIMS distinguishes rectal tissue types based on underlying lipid biology, and this can be translated in vivo by coupling it to TAMIS. There is a role for this technology in improving the efficacy of resection of early rectal cancers.

Organ Preservation in Rectal Cancer: The Patients' Perspective.

Organ preservation after a clinical complete response to radiochemotherapy is currently one of the most discussed topics in the management of rectal cancer. However, the patients' perspective has only been poorly studied so far. In this multicenter study, we examined 49 patients with locally advanced rectal cancer. The willingness to participate in an organ preservation study and the acceptance of the associated aspects such as intensified radiochemotherapy protocols, the need for close follow-up examinations and local regrowth rates were assessed. Attitudes were correlated with baseline quality of life parameters and psychological scales for “fear of progression”, “locus of control”, “depression”, and the “willingness to take risks”. A total of 83% of patients would consider the deferral of surgery in case of a clinical complete response (cCR). Three monthly follow-up studies and a 25% local regrowth rate are considered acceptable by 95% and 94% respectively. While 41% would be willing to exchange cure rates for a non-operative treatment strategy, a potentially more toxic radiochemotherapy in order to increase the probability of a cCR was the aspect with the lowest acceptance (55%). Psychological factors, in particular “locus of control” and “willingness to take risks”, influenced patient preferences regarding most of the assessed parameters. While in general a broad acceptance of an organ-preserving treatment can be expected, patient preferences and concerns regarding different aspects of this strategy vary widely and require specific consideration during shared decision making.

Planned organ preservation for early T2-3 rectal adenocarcinoma: A French, multicentre study

BackgroundNeoadjuvant chemoradiotherapy (nCRT) and watch-and-wait policy as reported by Habr-Gama are references for organ preservation in rectal cancer. To increase the clinical complete response (cCR) and reduce the local recurrence rates, we report a retrospective analysis of a prospective cohort of selected T2-3 tumours treated in three French institutions using contact X-ray brachytherapy (CXB) with nCRT. MethodsTumour selection was based on digital rectal examination (DRE), rigid rectoscopy, magnetic resonance imaging (MRI) and/or endorectal ultrasound. Adenocarcinoma T2-3 < 5 cm largest diameter, M0 were treated, all with organ preservation intent. CXB delivering 90 Gy/3 fractions/4 weeks was combined with CRT (capecitabine 50). Strict evaluation of tumour response using DRE and rectoscopy ± MRI was performed at regular interval with prolonged surveillance. FindingsBetween 2002 and 2016, 74 consecutive patients were treated (median age: 74 years. T2: 45 and T3: 29). A cCR or near-cCR (mainly rectal wall ulceration) was noted at week 14 in 71 patients (95%). A local excision was performed in 13 patients. Of three partial responses (PRs), one salvage anterior resection was performed. With a median follow-up of 3 years, local recurrence (mainly in the rectal wall) was seen in seven patients. The 3-year local recurrence rate was 10%, and the cancer-specific survival, 88%. Two patients underwent radical proctectomy for PR or local recurrence and 96% preserved their rectum. Grade III acute toxicity was recorded in five patients. Rectal bleeding was the main late toxicity (grade III in 12%). Bowel function was scored as good or excellent in 85% of patients. InterpretationCombining CXB and nCRT in selected early T2-T3 rectal cancers may safely provide a high rate of cCR, organ preservation, and good bowel function with a risk of local recurrence below 15%. Such an approach could be offered to operable patients as a planned option for organ preservation.

ASO Author Reflections: Decision Timing for Organ Preservation in Rectal Cancer After Chemoradiation.

ASO Author Reflections: Decision Timing for Organ Preservation in Rectal Cancer After Chemoradiation.