Stromal composition predicts recurrence of early rectal cancer after local excision

AIMS: After local excision of early rectal cancer, definitive lymph node status is not available. An alternative means for accurate assessment of recurrence risk is required to determine the most appropriate subsequent management. Currently used measures are suboptimal. We assess three measures of tumour stromal content to determine their predictive value after local excision in a well-characterised cohort of rectal cancer patients without prior radiotherapy. METHODS AND RESULTS: A total of 143 patients were included. Haematoxylin and eosin (H&E) sections were scanned for (i) deep neural network (DNN, a machine-learning algorithm) tumour segmentation into compartments including desmoplastic stroma and inflamed stroma; and (ii) digital assessment of tumour stromal fraction (TSR) and optical DNA ploidy analysis. 3' mRNA sequencing was performed to obtain gene expression data from which stromal and immune scores were calculated using the ESTIMATE method. Full results were available for 139 samples and compared with disease-free survival. All three methods were prognostic. Most strongly predictive was a DNN-determined ratio of desmoplastic to inflamed stroma >5.41 (P 36.5% (P = 0.037). CONCLUSIONS: The DNN-determined ratio of desmoplastic to inflamed ratio is a novel and powerful predictor of disease recurrence in locally excised early rectal cancer. It can be assessed on a single H&E section, so could be applied in routine clinical practice to improve the prognostic information available to patients and clinicians to inform the decision concerning further management.Publishe

Adjuvant radiotherapy after local excision of rectal cancer

BACKGROUND:Local excision is now accepted as a standard treatment option for certain patients with early rectal cancer. However, there is a higher risk of local recurrence than after radical surgery with total mesorectal excision. Adjuvant radiotherapy after local excision may reduce this excess risk, and yet retain the benefits of local excision, with rectal preservation. METHODS:A review of the literature pertaining to the use of adjuvant radiotherapy after local excision of rectal cancer and a discussion of current practice. RESULTS:We first considered local excision as a treatment option for early rectal cancer, looking at technical developments and the risks and benefits of organ preservation, in particular, the advantages for quality of life and the risk of leaving residual disease which may result in local recurrence. We then looked at reported outcomes for studies using adjuvant radiotherapy after local excision. Few of the studies routinely used modern endoscopic methods of local excision and only the recent used chemoradiation. Local recurrence rates after adjuvant radiotherapy have improved over time, with rates of around 3.5% in the recent studies. Adverse effects of adjuvant radiotherapy are not commonly described, but generally, they are relatively mild when described. We then discussed current practice regarding adjuvant radiotherapy, including pathological criteria, discussion of local recurrence risk with the patient and the importance of a surveillance regime to detect any recurrence at an early stage. CONCLUSION:We conclude that the current state of knowledge regarding adjuvant radiotherapy after local excision suggests a potential role in decreasing the risk of local recurrence but further studies are required to better define this effect, clarify which patients will gain the most benefit from this pathway, and identify those who should avoid exposure to the risks of radiotherapy

Outcomes following completion and salvage surgery for early rectal cancer: A systematic review

Objectives To establish outcomes after completion and salvage surgery following local excision in literature published since 2005, to inform decision-making when offering local excision. Background Local excision of early rectal cancer aims to offer cure while maintaining quality of life through organ preservation. However, some patients will require radical surgery, prompted by unexpected poor pathology or local recurrence. Consistent definition and reporting of these scenarios is poor. We propose the term “salvage surgery” for recurrence after local excision and “completion surgery” for poor pathology. Methods Electronic databases were searched in February 2016. Studies since 2005 describing outcomes for radical surgery following local excision of rectal cancer were included. Pooled and average values were obtained. Results A total of 23 studies included 262 completion and 165 salvage operations. Most completion operations were done within 4 weeks; local recurrence rate was 5% and overall disease recurrence rate was 14%. The majority of salvage operations for local recurrence were within 15 months of local excision, often following adjuvant treatment. Re-do local excision was used in 15%; APR was the most common radical procedure. Further local recurrence was uncommon (3%) but overall disease recurrence rate was 13%. Estimated 5-year survival was in the order of 50%. Heterogeneity was high among the studies. Conclusions Patients undergoing local excision must be informed of risks and expected outcomes, but better data on completion and salvage surgery are required to achieve this.</p

Quality of life after rectal-preserving treatment of rectal cancer

Aim Rectal-preserving strategies for managing rectal cancer are becoming more common for selected groups of patients. Oncological outcomes are similar, so long as patients are closely followed, and any local recurrence detected and managed promptly. Functional outcomes are now of increasing importance so patients can be appropriately counselled prior to treatment. We examine functional outcomes in patients managed by multimodal organ-preservation approaches allowing comparison of the full range of strategies. Materials and methods Patients attending for surveillance after any of four rectal-preserving treatments for rectal cancer (radiotherapy [RT], local excision [LE], RT then LE or LE then RT) were asked to complete a questionnaire assessing general quality of life and bowel, urinary and sexual function. Results 100 patients completed questionnaires: 34 managed by neoadjuvant RT followed by ‘watch and wait’, 40 by LE, and 26 who had composite treatment (18 LE + RT and eight RT + LE). Questionnaires were completed a median of 10 months (IQ range 6–33) following treatment. The LE only group tended to have better bowel function, while the composite groups fared worse; significant differences were noted in LARS and some bowel symptoms scores. Conclusion Bowel function appears better after LE alone compared with treatment strategies involving RT, and composite treatments have an additive effect on outcome impairment. Overall quality of life outcomes are good, despite the ongoing requirement for surveillance. As these treatments become more common it is important that patients can be better informed before deciding on a management pathway.</p

Modern management of T1 rectal cancer by TEM:a ten-year single-centre experience.

Aim Minimally-invasive, organ-sparing surgery has been used increasingly for early rectal cancer in recent years. However local recurrence remains a concern. This study presents a ten-year single-centre experience of recurrence after local excision for T1 rectal cancer. Method Data are collected prospectively on all patients undergoing local excision by transanal endoscopic microsurgery (TEM) in a single institution. Data covering a 10-year period were analysed. Results 192 patients underwent TEM for rectal cancer; 70 of these had T1 tumour in the TEM specimen and did not have pre-operative radiotherapy. Four were managed with completion surgery following TEM and a further six had radiotherapy, 60 underwent surveillance alone. Local recurrence occurred in six patients, three underwent salvage surgery. Estimated local recurrence at 3 years was 7.2% for the surveillance alone group. Conclusions Local recurrence rates were lower than previous studies. Better pre-operative assessment, more effective local excision surgery and post-operative radiotherapy may be contributory factors to a better-than-predicted outcome. Local excision should be offered as part of standard of care for T1 rectal cancer in the presence of good pre-operative selection and meticulous surveillance.</p

Radiotherapy after local excision of rectal cancer may offer reduced local recurrence rates

AIM:Early rectal cancer can be managed effectively with local excision, which is now the standard of care for many T1 lesions. However, the presence of unexpected adverse histopathological factors may indicate an increased risk of local recurrence, prompting consideration of completion radical surgery. Many patients are unfit or prefer to avoid radical surgery, relying instead on surveillance and early detection of recurrent disease. Recently, radiotherapy has shown promise as an adjuvant therapy in this group. This study assesses local recurrence rates after local excision with adjuvant radiotherapy at a single centre. METHOD:This was a retrospective review of a prospective database of all patients undergoing transanal endoscopic microsurgery (TEM) in a single institution. Data covering a 10-year period were analysed. RESULTS:Of 197 patients undergoing TEM for rectal cancer, 33 (17%) had adjuvant radiotherapy because of adverse histopathological features. At 3.2 years' median follow-up, there were three instances of local recurrence (9.1%). Estimated local recurrence at 1 and 3 years was 0% and 6.9%, compared to 16.8% and 21.2% in a propensity-score-matched group who were followed by surveillance alone. Local recurrence was diagnosed at a median of 23 months post-TEM in the radiotherapy group, compared to 8 months in the matched group. CONCLUSION:Radiotherapy after TEM is associated with a trend towards a reduced rate of local recurrence, even for high-risk disease. Radiotherapy would appear to offer a viable alternative to radical completion surgery in the presence of unforeseen adverse histopathological features, as long as a meticulous surveillance programme is in place