Non-operative Management Of Rectal Cancer Research Articles

Why every colorectal surgeon should learn endoluminal surgery

Endoscopic submucosal dissection (ESD) is an advanced therapeutic technique used to remove non-malignant polyps (NMP) and early cancers. Benefits include reducing unnecessary colectomies, cost, and morbidity of NMP treatment. Other roles for ESD and associated skills are likely to expand in the future, including in the non-operative management of rectal cancer. The learning curve is feasible with established training methods. Colorectal surgeons already perform routine endoscopy and manage endoscopic complications and endoscopically incurable lesions- endoluminal surgery (ELS) is a natural extension of this. Expanding technologies will only improve our ability to resect these lesions endoluminally moving forward. Collaboration with gastroenterologists and acquiring, rather than abandoning, this skillset is important and obtainable. Colorectal surgeons have the tools and professional duty to stay at the forefront of managing colorectal diseases endoscopically. Despite substantial barriers to mastering ELS, the value to our patients and profession means all colorectal surgeons should learn these techniques.

Operative trends following the adoption of nonoperative management of rectal cancer.

Differentiating clinical near-complete and complete responses (cCR) after neoadjuvant therapy (NT) is challenging in rectal cancer patients. We hypothesized that magnetic resonance imaging staging limitations for low rectal cancers may increase the proportion of abdominoperineal resection (APR) with permanent colostomy for those without a cCR. Single institution retrospective analysis of rectal cancer cases before and after adoption of nonoperative "watch and wait" (W&W) pathway. APR as a percentage of rectal resections was the primary outcome. There were 76 total mesorectal excisions (TME) in the pre-W&W group and 98 in the post-W&W group. NT was significantly more common in the post-W&W group. There was no significant difference in the APR primary outcome (pre-W&W APR 33.3% vs. post-W&W APR 26.5%, p = 0.482). APR patients had fewer complete TME grades (69.2% vs. 46.2%) and more pathologic complete responses (0% vs. 26.9%) in the post-W&W period. The cCR rate for patients with nonoperative management was 51.4% (n = 37) and 13.5% (n = 5) had regrowths, all of whom underwent salvage surgery. APR for those without a cCR to NT has not increased in the nonoperative management era. Balancing the pathologic complete response rate may require restaging some patients with clinical near-complete responses.

A Growing Divide? Social Determinants of the Use of Nonoperative Management of Rectal Cancer and Its Impact on Survival

IntroductionNonoperative management (NOM) of locally advanced rectal cancer was described as early as 2004. Initial national data demonstrated increase in utilization of NOM from 1998 to 2010, but newer national utilization data are not available. MethodsWe performed a retrospective cohort study using the National Cancer Database to assess utilization and 5-y overall survival (OS) of NOM of locally advanced rectal cancer. All patients had American Joint Committee on Cancer stage 2 or 3 rectal cancer, were over 40 y old, received both chemotherapy and radiation therapy, and were not being treated with palliative intent. Results74,780 patients were analyzed. 64,540 (86.2%) underwent a definitive resection, 10,330 (13.8%) had NOM. Utilization of NOM steadily increased from 11.3% in 2010 to 18.6% in 2018. Multivariate regression identified the highest predictors of utilization of NOM to be uninsured status, government insurance, Black race, and treatment at a community cancer center. Multivariate regression identified NOM as the highest hazard for mortality (hazard ratio = 2.286, confidence interval 2.209-2.366). After propensity score matching, the mean estimated 5-y OS was 52.0% for those managed operatively compared to 39.8% for those managed nonoperatively. ConclusionsFrom 2004 to 2018, the utilization of NOM of locally advanced rectal cancer significantly increased. However, there was a significant discrepancy in OS in comparison to surgical resection for these patients. Further study is needed to determine the long-term oncologic safety of NOM.

Is It Really Gone? Assessing Response to Neoadjuvant Therapy in Rectal Cancer.

Non-operative management of rectal cancer is a feasible and appealing treatment option for patients who develop a complete response after neoadjuvant therapy. However, identifying patients who are complete responders is often a challenge. This review aims to present and discuss current evidence and recommendations regarding the assessment of treatment response in rectal cancer. A review of the current literature on rectal cancer restaging was performed. Studies included in this review explored the optimal interval between the end of neoadjuvant therapy and restaging, as well as modalities of assessment and their diagnostic performance. The current standard for restaging rectal cancer is a multimodal assessment with the digital rectal examination, endoscopy, and T2-weighted MRI with diffusion-weighted imaging. Other diagnostic procedures under investigation are PET/MRI, radiomics, confocal laser endomicroscopy, artificial intelligence-assisted endoscopy, cell-free DNA, and prediction models incorporating one or more of the above-mentioned exams. Non-operative management of rectal cancer requires a multidisciplinary approach. Understanding of the robustness and limitations of each exam is critical to inform patient selection for that treatment strategy.

Emerging Role of Brachytherapy in the Non-operative Management of Rectal Cancer

Emerging Role of Brachytherapy in the Non-operative Management of Rectal Cancer

FDG-PET/MRI for Nonoperative Management of Rectal Cancer: A Prospective Pilot Study.

Nonoperative management (NOM) is increasingly utilized for rectal cancer patients with a clinical complete response (cCR) following total neoadjuvant therapy (TNT). The objective of this pilot study was to determine whether FDG-PET/MRI alters clinical response assessments among stage I-III rectal cancer patients undergoing TNT followed by NOM, relative to MRI alone. This prospective study included 14 subjects with new rectal cancer diagnoses. Imaging consisted of FDG-PET/MRI for initial staging, post-TNT restaging, and surveillance during NOM. Two independent readers assessed treatment response on MRI followed by FDG-PET/MRI. Inter-reader differences were resolved by consensus review. The reference standard for post-TNT restaging consisted of surgical pathology or clinical follow-up. 7/14 subjects completed post-TNT restaging FDG-PET/MRIs. 5/7 subjects had evidence of residual disease and underwent total mesorectal excision; 2/7 subjects had initial cCR with no evidence of disease after 12 months of NOM. FDG-PET/MRI assessments of cCR status at post-TNT restaging had an accuracy of 100%, compared with 71% for MRI alone, as FDG-PET detected residual tumor in 2 more subjects. Inter-reader agreement for cCR status on FDG-PET/MRI was moderate (kappa, 0.56). FDG-PET provided added value in 82% (9/11) of restaging/surveillance scans. Our preliminary data indicate that FDG-PET/MRI can detect more residual disease after TNT than MRI alone, with the FDG-PET component providing added value in most restaging/surveillance scans.

A Multidisciplinary Approach for the Personalised Non-Operative Management of Elderly and Frail Rectal Cancer Patients Unable to Undergo TME Surgery.

Simple SummaryTotal mesorectal excision is the cornerstone for rectal cancer curation. However, elderly and frail patients may not be able to undergo a surgical procedure. These patients often receive no treatment at all and are at risk for developing debilitating symptoms that impair quality of life. Recent developments in the non-operative management of rectal cancer have increased the possibilities to provide patients with an alternative treatment if surgery is not possible, in an effort to avoid the onset of debilitating symptoms, improve quality of life, and prolong survival. The heterogeneity within the elderly and frail population requires a patient-centred approach to optimise treatment. The aim of this narrative review was to discuss a multidisciplinary and patient-centred treatment approach for the personalised non-operative management of elderly and frail rectal cancer patients. The narrative review also provides a practical suggestion of a successfully implemented multidisciplinary clinical care pathway, based on a literature review.Despite it being the optimal curative approach, elderly and frail rectal cancer patients may not be able to undergo a total mesorectal excision. Frequently, no treatment is offered at all and the natural course of the disease is allowed to unfold. These patients are at risk for developing debilitating symptoms that impair quality of life and require palliative treatment. Recent advancements in non-operative treatment modalities have enhanced the toolbox of alternative treatment strategies in patients unable to undergo surgery. Therefore, a proposed strategy is to aim for the maximal non-operative treatment, in an effort to avoid the onset of debilitating symptoms, improve quality of life, and prolong survival. The complexity of treating elderly and frail patients requires a patient-centred approach to personalise treatment. The main challenge is to optimise the balance between local control of disease, patient preferences, and the burden of treatment. A comprehensive geriatric assessment is a crucial element within the multidisciplinary dialogue. Since limited knowledge is available on the optimal non-operative treatment strategy, these patients should be treated by dedicated multidisciplinary rectal cancer experts with special interest in the elderly and frail. The aim of this narrative review was to discuss a multidisciplinary patient-centred treatment approach and provide a practical suggestion of a successfully implemented clinical care pathway.

Outcomes of Patients With Local Regrowth After Nonoperative Management of Rectal Cancer After Neoadjuvant Chemoradiotherapy.

Clinical complete responders after chemoradiation for rectal cancer are increasingly being managed by a watch-and-wait strategy. Nonetheless, a significant proportion will experience a local regrowth, and the long-term oncological outcomes of these patients is not totally known. The purpose of this study was to analyze the outcomes of patients who submitted to a watch-and-wait strategy and developed a local regrowth, and to compare these results with sustained complete clinical responders. This was a retrospective study. Single institution, tertiary cancer center involved in alternatives to organ preservation. Patients with a biopsy-proven rectal adenocarcinoma (stage II/III or low lying cT2N0M0 at risk for an abdominoperineal resection) treated with chemoradiation who were found at restage to have a clinical complete response. Rectal cancer patients treated with chemoradiation who underwent a watch-and-wait strategy (without a full thickness local excision) and developed a local regrowth were compared to the remaining patients of the watch-and-wait strategy. Overall survival between groups, incidence of regrowth' and results of salvage surgery. There were 67 patients. Local regrowth occurred in 20 (29.9%) patients treated with a watch-and-wait strategy. Mean follow-up was 62.7 months. Regrowth occurred at mean 14.2 months after chemoradiation, half of them within the first 12 months. Patients presented with comparable initial staging, lateral pelvic lymph-node metastasis, and extramural venous invasion. The regrowth group had a statistically nonsignificant higher incidence of mesorectal fascia involvement (35.0% vs 13.3%, p = 0.089). All regrowths underwent salvage surgery, mostly (75%) a sphincter-sparing procedure. 5-year overall survival was 71.1% in patients with regrowth and 91.1% in patients with a sustained complete clinical response (p = 0.027). This study was limited by its retrospective evaluation of patient selection for a watch-and-wait strategy and outcomes, as well as its small sample size. Local regrowth is a frequent event when following a watch-and-wait policy (29.9%); however, patients could undergo salvage surgical treatment with adequate pelvic control. In this series, overall survival showed a statistically significant difference from patients managed with a watch-and-wait strategy who experienced a local regrowth compared to those who did not. See Video Abstract at http://links.lww.com/DCR/B773.RESULTADOS DE LOS PACIENTES CON REBROTE LOCAL, DESPUÉS DEL MANEJO NO QUIRÚRGICO DEL CÁNCER DE RECTO, DESPUÉS DE LA QUIMIORRADIOTERAPIA NEOADYUVANTEANTECEDENTES:Los respondedores clínicos completos, después de la quimiorradiación para el cáncer de recto, se tratan cada vez más mediante una estrategia de observación y espera. No obstante, una proporción significativa experimentará un rebrote local y los resultados oncológicos a largo plazo de estos pacientes, no se conocen por completo.OBJETIVO:El propósito de este estudio, fue analizar los resultados de los pacientes sometidos a una estrategia de observación y espera, que desarrollaron un rebrote local, y comparar estos resultados con respondedores clínicos completos sostenidos.DISEÑO:Este fue un estudio retrospectivo.ENTORNO CLINICO.Institución única, centro oncológico terciario involucrado en alternativas a la preservación de órganos.PACIENTES:Pacientes con un adenocarcinoma de recto comprobado por biopsia (estadio II / III o posición baja cT2N0M0, en riesgo de resección abdominoperineal), tratados con quimiorradiación, y que durante un reestadiaje, presentaron una respuesta clínica completa.INTERVENCIONES:Los pacientes con cáncer de recto tratados con quimiorradiación, sometidos a una estrategia de observación y espera (sin una escisión local de espesor total) y que desarrollaron un rebrote local, se compararon con los pacientes restantes de la estrategia de observación y espera.PRINCIPALES MEDIDAS DE VALORACION:Supervivencia global entre los grupos, incidencia de rebrote y resultados de la cirugía de rescate.RESULTADOS:Fueron 67 pacientes. El rebrote local ocurrió en 20 (29,9%) pacientes tratados con una estrategia de observación y espera. El seguimiento medio fue de 62,7 meses. El rebrote se produjo a la media de 14,2 meses después de la quimiorradiación, la mitad de ellos dentro de los primeros 12 meses. Los pacientes se presentaron con una estadificación inicial comparable, metástasis en los ganglios linfáticos pélvicos laterales e invasión venosa extramural. El grupo de rebrote tuvo una mayor incidencia estadísticamente no significativa de afectación de la fascia mesorrectal (35,0 vs 13,3%, p = 0,089). Todos los rebrotes se sometieron a cirugía de rescate, en su mayoría (75%) con procedimiento de preservación del esfínter. La supervivencia global a 5 años fue del 71,1% en pacientes con rebrote y del 91,1% en pacientes con una respuesta clínica completa sostenida (p = 0,027).LIMITACIONES:Evaluación retrospectiva de la selección de pacientes para una estrategia y resultados de observar y esperar, tamaño de muestra pequeño.CONCLUSIONES:El rebrote local es un evento frecuente después de la política de observación y espera (29,9%), sin embargo los pacientes podrían someterse a un tratamiento quirúrgico de rescate con un adecuado control pélvico. En esta serie, la supervivencia global mostró una diferencia estadísticamente significativa de los pacientes manejados con una estrategia de observación y espera que experimentaron un rebrote local, en comparación con los que no lo hicieron. Consulte Video Resumen en http://links.lww.com/DCR/B773. (Traducción-Dr. Fidel Ruiz Healy).

Tumor Volume Predicts for Pathological Complete Response in Rectal Cancer Patients Treated With Neoadjuvant Chemoradiation

<h3>Purpose/Objective(s)</h3> Currently, neoadjuvant chemoradiation (CRT) followed by total mesorectal excision is a standard treatment for patients with stage II and III rectal cancer. However, non-operative management of rectal cancer is an emerging approach to allow patients to preserve their anal sphincter. Factors that may help identify patients most likely to have a pathological complete response (pCR) would be helpful for physicians and patients considering a non-operative approach. <h3>Materials/Methods</h3> A total of 377 patients from our institution who had clinical stage II or III rectal cancer treated with neoadjuvant chemoradiation were included in the analysis. Patients were grouped based on their pCR status. Clinical parameters including overall stage, gross tumor volume (GTV), and radiation dose were analyzed by univariate and multivariate analysis, with pCR being the dependent variable. A Receiver Operator Characteristic (ROC) curve was generated in order to identify a tumor volume cutoff with the highest sensitivity for predicting pCR. <h3>Results</h3> The cohort had a median age at diagnosis of 61 years, 68% were male, and 85% presented with stage III disease. 68 of the 377 patients (18%) included in our analysis achieved pCR. A tumor volume of < 18.7 cc is highly sensitive (90%) for predicting pCR. Additionally, on multivariate analysis, a GTV of < 18.7 cc (odds ratio (OR) = 3.1, 95% confidence interval (CI) = 1.613-6.356, <i>P</i> = 0.001) was significantly associated with an increased rate of pCR. Overall stage (<i>P</i> = 0.026) was also significantly associated with pCR, while prescribed dose (<i>P</i> = 0.45) did not appear to impact pCR rates. <h3>Conclusion</h3> Our analysis identified a GTV volume of < 18.7 cc as a strong predictor for pCR in stage II and III rectal cancer patients receiving neoadjuvant chemoradiation, which will be helpful in identifying potential candidates for non-operative management.

Rectal cancer: Watch-and-wait and continuing the rectal-preserving strategy with local excision for incomplete response or limited regrowth

BackgroundDeferral of conventional surgery for rectal cancer after neo-adjuvant chemo-radiotherapy is gaining increasing interest, particularly for patients who are too frail to undergo major surgery but also those who wish to avoid the adverse effects of major surgery.We elected to undertake a pragmatic approach to include all comers in a cohort with the aim of reflecting the clinical outcomes for patients on a deferral from conventional rectal surgery pathway, treated with neo-adjuvant chemo-radiation (CRT) with or without selective local excision (LE) offered to those who failed to demonstrate a complete clinical response (cCR). MethodsRectal cancer patients treated with neo-adjuvant CRT were stratified to a group of complete responders to CRT on a “watch and wait” (WW) pathway and a group who were treated with an additional local excision for persistent tumour. ResultsRegrowth was noted in 26% (11/42) in the WW group after 2 years surveillance, disease free survival was 94.5% (80–99%) at 1 year and 74.9% (44–76.4%) at 3 years.Recurrence was noted in 45% (10/22) in the CRT + LE group, disease free survival at 1 and 3 years was 74% (53.4–88.1) and 66.2% (45.6–82.4) respectively. ConclusionA WW strategy for cCR is a viable pathway in the non-operative management of rectal cancer. We found the use of CRT + LE is a useful option for those who hope to avoid surgery but caution should be exercised due to substantially higher risk of recurrence.

PH-0162: Is there a radiation dose-response relationship for non-operative management of rectal cancer?

PH-0162: Is there a radiation dose-response relationship for non-operative management of rectal cancer?

Non-surgical “Watch and Wait” Approach to Rectal Cancer

The standard of care for locally advanced rectal cancer is preoperative chemoradiation (CRT) followed by total mesorectal excision (TME). Patients who achieve a pathologic complete response (pCR) to CRT have favorable oncologic outcomes. Given the significant morbidity and long-term effects on quality of life associated with radical resection, the role of surgery in the subgroup of patients with a clinical complete response (cCR), of whom a significant proportion may have a pCR, is under debate. An emerging tailored approach to treatment is a “watch and wait” strategy in patients who have a cCR after CRT with the goal of organ preservation. However, concordance between a cCR and pCR is not highly reliable, and improved multimodality prediction algorithms are needed to better predict which patients have achieved a pCR and can therefore safely undergo a “watch and wait” approach. We review the current data on non-operative management of rectal cancer and ongoing controversies associated with this approach.

Trimodal Therapy Approaches for Localized Rectal Cancer

Excellent long-term outcomes and manageable toxicity are being achieved with contemporary treatment strategies for rectal cancer. Short-course radiotherapy is now an acceptable standard. Total neoadjuvant therapy (TNT), which incorporates induction or consolidation chemotherapy, has improved the delivery of treatment regiments. TNT is now a standard of care, although the sequencing of radiation and chemotherapy in TNT, appropriate amount of chemotherapy in TNT, and addition of irinotecan to the regimen are still being debated. Nonoperative management of rectal cancer appears to be a safe option for select patients, but it is not yet an NCCN recommendation. In addition, the omission of radiation is being evaluated as a treatment option in some cases.

Feasibility of Non-Operative Management of Rectal Cancer in a Rural Population

Feasibility of Non-Operative Management of Rectal Cancer in a Rural Population

Image Guided Adaptive Endorectal Brachytherapy in the Nonoperative Management of Patients With Rectal Cancer

Organ preservation or nonoperative management of rectal cancer is of growing interest. Image guided adaptive endorectal brachytherapy is a radiation dose escalation modality: we explored its role in elderly patients unfit for surgery and patients refusing surgery. In this registry study, patients with rectal cancer who were ineligible for surgery received 40 Gy in 16 fractions of pelvic external beam radiation therapy. They subsequently received 3 weekly image guided adaptive brachytherapy boosts of 10 Gy to the residual tumor, for a total of 30 Gy in 3 fractions. Complete clinical response (cCR) and local control were the primary endpoints. 94 patients were included; the median age was 81.1 years. With a median follow-up of 1.9 years, the proportion of cCR was 86.2%, the tumor regrowth proportion was 13.6%, and the cumulative incidence of local relapse was 2.7% at 1 year and 16.8% at 2 years. When considering responders and nonresponders, the 2-year local control was 71.5%. The overall survival at 2 years was 63.6%. Acute rectal grade 1 to 2 toxicity included all patients: 12.8% of patients had late bleeding requiring iron replacement, blood transfusions, or argon plasma therapy. Results of this registry study, evaluating radiation dose escalation for elderly medically unfit patients with unselected tumors, reveal that a high proportion of patients achieved cCR with a manageable toxicity profile. This technology will likely contribute to the challenging nonoperative management paradigm of rectal cancer.

Non-operative management of rectal cancer

Despite advances in technique, surgical resection of rectal cancer remains a morbid procedure that can lead to a profound decrease in a patient's quality of life. A novel method of management, termed “Non-operative management” (NOM), mirrors the management of anal carcinoma. Patients undergo definitive treatment with only chemotherapy and radiation, with resection reserved only for salvage. Current data is encouraging- both in reduction in morbidity and similar, if not superior oncologic results. However, there are a number of barriers to the wide adoption of this practice. This manuscript seeks to describe the rationale and execution of NOM as well as present the current data and pitfalls of the approach.

Watch and Wait Strategy for Rectal Cancer: 15 Years After the First Published Study. Are We any Closer to the Non-operative Management of Rectal Cancer?

Introduction: Over time, the management of rectal cancer has undoubtedly evolved with the use of neoadjuvant radiochemotherapy. Material and method: The P.I.C.O.S guidelines were used to structure the questions and the research topic as to attain clinical validity. The results of the research were filtered in accordance with the PRISMA checklist. Results: We identified 42 papers. After screening 27 papers were used to complete the analysis. Discussion: There is an increased interest towards the non-operative management of rectal cancer, as up to 25% of patients with preoperative radiochemotherapy have demonstrated complete pathological response (absence of tumor cells on the operative specimens). This information leads to the tantalizing idea that in some cases, surgery can be avoided. Unfortunately, there is a lack of quality data to support this view. Due to increased interest in this subject, an international database in which patients with w w therapy can be enrolled and monitored. Up to now, the database contains over 900 patients. Also, quality prospective trials are emerging. Conclusion: Even with all these recent efforts, the wide-use of this therapy is precluded due to the absence of a standardized evaluation of these patients in the follow-up period.

MicroRNA molecular profiling identifies potential signaling pathways conferring resistance to chemoradiation in locally-advanced rectal adenocarcinoma.

PurposeThere has been growing interest in using chemoradiation (CRT) for non-operative management of rectal cancer, and identifying patients who might benefit most from this approach is crucial. This study identified miRNAs (miRs) associated with clinical outcomes and treatment resistance by evaluating both pre- and post-CRT expression profiles.MethodsForty patients, 9 with pathologic complete response (pCR) and 31 with pathologic incomplete response (pIR) were included. MicroRNA was extracted from 40 pre-therapy tumor samples and 31 post-chemoradiation surgical samples with pathologic incomplete response (pIR). A generalized linear model was used to identify miRs associated with pCR. A linear mixed effects model was used to identify miRs differentially expressed before and after treatment. miR expression was dichotomized at the mean and clinical outcomes were evaluated using Cox proportional hazard modeling.ResultsNine miRs were associated with pCR (p<0.05), but none were significant after false discovery rate correction. Among patients with pIR, 68 miRs were differentially expressed between the pre and post-CRT groups (FDR p<0.05). Ingenuity pathway analysis (IPA) demonstrated multiple signaling networks associated with pIR, including p38MAPK, TP53, AKT, IL-6, and RAS. Increased let-7b was correlated with increased distant metastasis (DM), worse relapse-free survival (RFS), and worse overall survival (OS) (p<0.05).ConclusionsNo miRs were significantly correlated with pCR. We identified miRs that were differentially expressed between pre- and post-CRT tumor samples, and these miRs implicated multiple signaling pathways that may confer resistance to CRT. In addition, we identified an association between increased let-7b and worse clinical outcomes (DM, DFS, OS).

Non-operative management of rectal cancer: understanding tumor biology.

The management of locally-advanced rectal cancer involves a combination of chemotherapy, chemoradiation, and surgical resection to provide excellent local tumor control and overall survival. However, aspects of this multimodality approach are associated with significant morbidity and long-term sequelae. In addition, there is growing evidence that patients with a clinical complete response to chemotherapy and chemoradiation treatments may be safely offered initial non-operative management in a rigorous surveillance program. Weighed against the morbidity and significant sequelae of rectal resection, recognizing how to best optimize non-operative strategies without compromising oncologic outcomes is critical to our understanding and treatment of this disease.

Surgery Still Preferred Over Non-Operative Management of Rectal Cancer

Surgery Still Preferred Over Non-Operative Management of Rectal Cancer