Organ preservation in rectal cancer - Challenges and future strategies.
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ABSTRACT:
SUBMITTER: Gani C
PROVIDER: S-EPMC5893528 | biostudies-literature | 2017 Apr
REPOSITORIES: biostudies-literature
Publications
Organ preservation in rectal cancer - Challenges and future strategies.
Gani C C Bonomo P P Zwirner K K Schroeder C C Menegakis A A Rödel C C Zips D D
Clinical and translational radiation oncology 20170323
Neoadjuvant radiochemotherapy with subsequent total mesorectal excision is the standard of care for locally advanced rectal cancer. While this multimodal strategy has decreased local recurrences rates below 5%, long-term morbidities are considerable in terms of urinary, sexual or bowel functioning. At the same time approximately 10-20% of patients have no evidence of residual tumour in their surgical specimen. Pioneering studies from Brazil have suggested that surgery can safely be omitted in ca ...[more]
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Project description:Standard use of neoadjuvant chemoradiotherapy, total mesorectal excision, and postoperative adjuvant chemotherapy in locally advanced rectal cancer has tremendously improved oncologic outcomes over the past several decades. However, these improvements come with costs of significant morbidity and poor quality of life. Along with developments in imaging techniques, clinical experience and evidence have identified a certain subgroup of patients that have exceptionally good clinical outcomes while preserving quality of life. Driven by patient demand and interest in preserving quality of life, numerous organ preservation treatment strategies for managing rectal cancer are rapidly evolving. Herein, the flow of research in organ preservation strategies and counter arguments are discussed.
| S-EPMC6529751 | biostudies-literature
Project description:A proportion of patients with rectal cancer who undergo neoadjuvant treatment end up with a complete pathological response. Because these patients have excellent oncological outcomes, many have questioned if surgical treatment in this population constitutes overtreatment. There is growing interest in watch and wait with selective organ preservation for rectal cancer patients. We review the fundamentals and key considerations of this approach including patient selection, available treatment regimens, assessment of response, long-term monitoring of response, and long-term oncological and functional outcomes.
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Project description:Background:Total mesorectal excision (tme) is the current standard of care for the treatment of rectal cancer. However, that surgery is associated with significant morbidity and mortality. Clinicians and patients are seeking alternatives to radical resection. Currently, prevalent organ-sparing strategies under investigation include local excision and nonoperative management (nom). Methods:We reviewed the current evidence in the literature to create an overview of the use of transanal endoscopic surgery and watch-and-wait strategies in the modern management of rectal cancer. Results:Compared with radical resection, transanal endoscopic surgery in patients with early rectal cancer (cT1) having favourable histopathologic features is associated with an increased risk of local recurrence, but no difference in 5-year survival. In patients with T2 or early T3 cancer, strategies that use neoadjuvant or adjuvant therapy as adjuncts to local excision are under evaluation. Nonoperative management is a new option for patients who experience a complete clinical response after neoadjuvant chemoradiotherapy (ncrt). The selection criteria that will appropriately identify patients for whom nom will succeed are not established. Conclusions:Local excision is appropriate for early rectal cancer with favourable histopathologic features. Although organ-preserving strategies are promising, the quality of the evidence to date is insufficient to replace the current standard care in most patients. Patients should be offered nom in the safe setting of a clinical trial or registry. Rigorous follow-up, including endoscopy and imaging at frequent intervals is recommended when radical resection is forgone.
| S-EPMC6878939 | biostudies-literature
Project description: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.
| S-EPMC6524150 | biostudies-literature
Project description:Non-operative management of rectal cancer is increasingly being used in selected patients. Most reports include patients treated with chemoradiotherapy (CRT) before inclusion into a Watch & Wait (W&W) programme. The aim of this study was to report outcomes from a single-centre W&W programme involving a large cohort of patients. Patients treated with chemoradiotherapy (CRT) or short-course radiotherapy (SCRT) with or without chemotherapy, between 2008 and 2020, who showed signs of a clinical complete response (cCR) were reviewed. Patients were assessed using digital rectal examination, flexible endoscopy, carcinoembryonic antigen measurement, MRI, and CT imaging, discussed at the multidisciplinary tumour board meeting, and followed up in a dedicated W&W programme as from 2015. Outcomes including regrowth and 3-year survival (time to regrowth or death) were prospectively evaluated. Of 142 patients who were assessed, 88 fulfilled the criteria for cCR. Treatment before cCR included CRT, SCRT with chemotherapy, and SCRT alone in 16 (18 per cent), 28 (32 per cent), and 44 (50 per cent) patients, respectively. Patients treated with CRT and SCRT with chemotherapy had more advanced clinical T- and N-stage, compared with patients treated with SCRT alone (clinical T-stage > 2: 81 per cent and 89 per cent versus 47 per cent, respectively; clinical N-stage > 0: 75 per cent and 93 per cent versus 68 per cent, respectively). Overall rate of regrowth was 19 per cent, with 31 per cent, 21 per cent, and 14 per cent following CRT, SCRT with chemotherapy, and SCRT alone, respectively. Uni- and multivariable analyses evaluating the clinical parameters revealed no statistically significant associations with risk of local regrowth. All but one patient with regrowth underwent salvage surgery. The 3-year survival rate (death with regrowth as competing risk) was 93 per cent, with no significant difference between treatment groups. In this cohort of W&W patients, the vast majority received SCRT with or without chemotherapy and results consistent with previous W&W reports were obtained. No statistically significant differences in terms of regrowth rate were obtained when comparing CRT, SCRT with chemotherapy, and SCRT alone. SCRT can induce sustained cCR and may precede a W&W strategy.
| S-EPMC8536864 | biostudies-literature
Project description:BackgroundThe therapeutic modalities for nonmetastatic rectal cancer are presently undergoing major changes. The standard treatment is multidisciplinary, combining radiotherapy, chemotherapy, and surgery. The aim of this minireview is to provide an update on the place of organ preservation in the treatment of nonmetastatic rectal cancer in 2022.Main textThe multimodal strategy based on initial radiochemotherapy followed by radical surgery with excision of the mesorectum has improved oncological results but at the expense of morbidity and sequelae altering life quality. The strategy of rectal preservation has been proposed since the 2000s after the publication of the results of the Brazilian study that proposed a simple surveillance after radiochemotherapy without surgery in good responders. In fact, preoperative radiochemotherapy was able to obtain a complete histological response in 10 to 30% of case. In view of this non-negligible percentage of tumor sterilization, which may well increase with the standardization of total neoadjuvant treatment, a strategy of organ preservation can be proposed in these patients to avoid morbidity and postoperative sequelae.Short conclusionThis nonoperative approach is currently widely studied in certain patients who have a complete response (clinical, endoscopic, and radiological). However, the selection of these patients is not simple and still complex.
| S-EPMC10123594 | biostudies-literature
Project description:BackgroundTotal mesorectal excision (TME) remains commonplace for T1-2 rectal cancer owing to fear of undertreating a small proportion of patients with node-positive disease. Molecular stratification may predict cancer progression. It could be used to select patients for organ-preserving surgery if specific biomarkers were validated.MethodsGene methylation was quantified using bisulphite pyrosequencing in 133 unirradiated rectal cancer TME specimens. KRAS mutation and microsatellite instability status were also defined. Molecular parameters were correlated with histopathological indices of disease progression. Predictive models for nodal metastasis, lymphovascular invasion (LVI) and distant metastasis were constructed using a multilevel reverse logistic regression model.ResultsMethylation of the retinoic acid receptor ? gene, RARB, and that of the checkpoint with forkhead and ring finger gene, CHFR, was associated with tumour stage (RARB: 51·9 per cent for T1-2 versus 33·9 per cent for T3-4, P?<?0·001; CHFR: 5·5 per cent for T1-2 versus 12·6 per cent for T3-4, P?=?0·005). Gene methylation associated with nodal metastasis included RARB (47·1 per cent for N- versus 31·7 per cent for N+; P?=?0·008), chemokine ligand 12, CXCL12 (12·3 per cent for N- versus 8·9 per cent for N+; P?=?0·021), and death-associated protein kinase 1, DAPK1 (19·3 per cent for N- versus 12·3 per cent for N+; P?=?0·022). RARB methylation was also associated with LVI (45·1 per cent for LVI- versus 31·7 per cent for LVI+; P?=?0·038). Predictive models for nodal metastasis and LVI achieved sensitivities of 91·1 and 85·0 per cent, and specificities of 55·3 and 45·3 per cent, respectively.ConclusionThis methylation biomarker panel provides a step towards accurate discrimination of indolent and aggressive rectal cancer subtypes. This could offer an improvement over the current standard of care, whereby fit patients are offered radical surgery.
| S-EPMC4282074 | biostudies-literature
Project description:Total neoadjuvant therapy (TNT) is an evolving treatment schedule for locally advanced rectal cancer (LARC), allowing for organ preservation in a relevant number of patients in the case of complete response. Patients who undergo this so-called "watch and wait" approach are likely to benefit regarding their quality of life (QoL), especially if definitive ostomy could be avoided. In this work, we performed the first cost-effectiveness analysis from the patient perspective to compare costs for TNT with radical resection after neoadjuvant chemoradiation (CRT) in the German health care system. Individual costs for patients insured with a statutory health insurance were calculated with a Markov microsimulation. A subgroup analysis from the prospective "FinTox" trial was used to calibrate the model's parameters. We found that TNT was less expensive (-1540 EUR) and simultaneously resulted in a better QoL (+0.64 QALYs) during treatment and 5-year follow-up. The average cost for patients under TNT was 4711 EUR per year, which was equivalent to 3.2% of the net household income. CRT followed by resection resulted in higher overall costs for ostomy care, medication and greater loss of earnings. Overall, TNT appeared to be more efficacious and cost-effective from a patient's point of view in the German health care system.
| S-EPMC11011197 | biostudies-literature
Project description:BACKGROUND:Transanal 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. METHODS:In 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. RESULTS:Forty-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. CONCLUSIONS:REIMS 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.
| S-EPMC7326832 | biostudies-literature
Project description:BackgroundHigh dose chemoradiotherapy offers a curative chance for patients with rectal cancer that are unfit or unwilling to undergo surgical resection, yet its long-term survival and functional outcomes have been rarely investigated.MethodsPatients with non-metastatic rectal adenocarcinoma who received pelvic radiation for curative intent from April 2006 to July 2017 were retrospectively investigated. Survival rates were analyzed using the Kaplan-Meier method. Quality of life and functional outcomes were evaluated using the EORTC quality of life questionnaire.ResultsA total of 57 patients were included, with a median age of 59.0 (range, 29-84) years. The numbers of patients who were diagnosed as stage I, II and III were 5 (8.8%), 16 (28.1%) and 36 (63.2%), respectively. 53 (93.0%) patients had tumor located within 5 cm from the anal verge. All patients received fluorouracil-based concurrent chemoradiotherapy with a median radiation dose of 80 (range, 60-86) Gy. All kinds of grade 3-4 adverse events occurred in 18 (31.6%) patients. 42 (73.7%) patients achieved a clinical complete response after chemoradiotherapy. After a median follow-up of 43.5 (range 14.9-163.2) months, 12 (21.1%) patients had local progression and 11 (19.3%) developed distant metastasis. The 3-year local recurrence-free survival and distant metastasis-free survival were 77.3% (95% CI, 65.7-88.8%) and 79.2% (95% CI, 68.2-90.2%), while the 3-year progression-free survival, cancer-specific survival, overall survival were 61.9% (95% CI, 48.8-75.0%), 93.1% (95% CI, 85.8-100.0%) and 91.4% (95% CI, 83.6-99.2%), respectively. For patients who had tumor located within 3 cm from the anal verge, the sphincter preservation rate was 85.3% at last follow-up. Long-term adverse events mainly were anal blood loss. 21 patients completed the quality-of-life questionnaire and had a score of the global health status of 78.57 ± 17.59. Of them, 95.2% reported no urinary incontinence and 85.7% reported no fecal incontinence.ConclusionsHigh dose chemoradiation demonstrated promising survival outcomes with acceptable short-term and long-term side effects, and satisfying long-term functional outcomes and quality of life. It could be considered as a non-invasive alternative for rectal cancer patients who refuse surgery.
| S-EPMC9118735 | biostudies-literature