Surgical Outcomes after Radiotherapy in Rectal Cancer.

Over the past decade, the treatment of rectal cancer has changed considerably. The implementation of TME surgery has, in addition to decreasing the number of local recurrences, improved surgical morbidity and mortality. At the same time, the optimisation of radiotherapy in the preoperative setting has improved oncological outcomes even further, although higher perineal infection rates have been reported. Radiotherapy regimens have evolved through the adjustment of radiotherapy techniques and fields, increased waiting intervals, and, for more advanced tumours, adding chemotherapy. Concurrently, imaging techniques have significantly improved staging accuracy, facilitating more precise selection of advanced tumours. Although chemoradiotherapy does lead to the downsizing and -staging of these tumours, a very clear effect on sphincter-preserving surgery and the negative resection margin has not been proven. Aiming to decrease distant metastasis and improve overall survival for locally advanced rectal cancer, systemic chemotherapy can be added to radiotherapy, known as total neoadjuvant treatment (TNT). High complete response rates, both pathological (pCR) and clinical (cCR), are reported after TNT. Patients who follow a Watch & Wait program after a cCR can potentially avoid surgical morbidity and colostomy. For both early and more advanced tumours, trials are now investigating optimal regimens in an attempt to offer organ preservation as much as possible. Multidisciplinary deliberation should include patient preference, treatment toxicity, and likelihood of end colostomy, but also the burden of intensive surveillance in a W&W program.

Oncological outcomes after a pathological complete response following total neoadjuvant therapy or chemoradiotherapy for high-risk locally advanced rectal cancer in the RAPIDO trial.

BACKGROUND: A pathological complete response (pCR) following chemoradiation (CRT) or short-course radiotherapy (scRT) leads to a favourable prognosis in patients with rectal cancer. Total neo-adjuvant therapy (TNT) doubles the pCR rate, but it is unknown whether oncological outcomes remain favourable and whether the same characteristics are associated with pCR as after CRT. METHODS: Comparison between patients with pCR in the RAPIDO trial in the experimental [EXP] (scRT, chemotherapy, surgery, as TNT) and standard-of-care treatment [STD] (CRT, surgery, postoperative chemotherapy depending on hospital policy) groups. Primary and secondary outcomes were time-to-recurrence (TTR), overall survival (OS) and association between patient, tumour, and treatment characteristics and pCR. RESULTS: Among patients with a resection within six months after preoperative treatment, 120/423 (28%) [EXP] and 57/398 (14%) [STD] achieved a pCR. Following pCR, 5-year cumulative TTR and OS rates in the EXP and STD arms were 8% vs. 7% (hazard ratio 1.04, 95%CI 0.32-3.38) and 94% vs. 93% (hazard ratio 1.41, 95%CI 0.51-3.92), respectively. Besides the EXP treatment (odds ratio 2.70, 95%CI 1.83-3.97), pre-treatment carcinoembryonic antigen (CEA) <5, pre-treatment tumour size <40 mm and cT2 were associated with pCR. Distance from the anal verge was the only characteristic with a statistically significant difference in association with pCR between the EXP and STD treatment (Pinteraction=0.042). pCR rates did not increase with prolonged treatment time. CONCLUSIONS: The doubled pCR rate of TNT compared to CRT results in similar oncological outcomes. Characteristics associated with pCR are the EXP treatment, normal CEA, and small tumour size.

Complete response rates in rectal cancer: Temporal changes over a decade in a population-based nationwide cohort.

INTRODUCTION: In the past decade many changes in neoadjuvant treatment for patients with rectal cancer have taken place and are expected to impact complete response rates. The aim of this study was to investigate the impact on pathological, and overall, complete response rates in a nationwide population-based cohort, in relation to changes in neoadjuvant treatment and the start of a Watch & Wait (WoW) study. MATERIALS AND METHODS: A nationwide register study using prospectively collected data from the Swedish Colorectal Cancer Register between 2009 and 2020. Patients with rectal cancer stage I-III with a ypT0N0 in the resected specimen after neoadjuvant treatment and clinical complete responders from the yearly inclusion data of the national WoW study were included. Temporal changes in pathological and overall complete response rates were analysed, and differences in neoadjuvant treatment regimens over time and per region were studied. RESULTS: Between 2009 and 2020 the pathological complete response rate for rectal cancer remained similar (Mann-Kendall tau of 0.091, p = 0.68) while the overall complete response rate increased significantly from 3.0% to 9.6% (Mann-Kendall tau of 0.818, p < 0.001). The pathological complete response rate for patients receiving short course radiotherapy followed by chemotherapy was reduced by 50% after the introduction of the WoW study. CONCLUSIONS: During the studied time period the overall complete response rate increased significantly presumably due to changes in national neoadjuvant treatment regimens. Since the start of the national WoW study clinical complete response seem to partly replace pathological complete response.

Baseline and early digital [ 18 F]FDG PET/CT and multiparametric MRI contain promising features to predict response to neoadjuvant therapy in locally advanced rectal cancer patients: a pilot study.

OBJECTIVE: In this pilot study, we investigated the feasibility of response prediction using digital [ 18 F]FDG PET/computed tomography (CT) and multiparametric MRI before, during, and after neoadjuvant chemoradiation therapy in locally advanced rectal cancer (LARC) patients and aimed to select the most promising imaging modalities and timepoints for further investigation in a larger trial. METHODS: Rectal cancer patients scheduled to undergo neoadjuvant chemoradiation therapy were prospectively included in this trial, and underwent multiparametric MRI and [ 18 F]FDG PET/CT before, 2 weeks into, and 6-8 weeks after chemoradiation therapy. Two groups were created based on pathological tumor regression grade, that is, good responders (TRG1-2) and poor responders (TRG3-5). Using binary logistic regression analysis with a cutoff value of P  ≤ 0.2, promising predictive features for response were selected. RESULTS: Nineteen patients were included. Of these, 5 were good responders, and 14 were poor responders. Patient characteristics of these groups were similar at baseline. Fifty-seven features were extracted, of which 13 were found to be promising predictors of response. Baseline [T2: volume, diffusion-weighted imaging (DWI): apparent diffusion coefficient (ADC) mean, DWI: difference entropy], early response (T2: volume change, DWI: ADC mean change) and end-of-treatment presurgical evaluation MRI (T2: gray level nonuniformity, DWI: inverse difference normalized, DWI: gray level nonuniformity normalized), as well as baseline (metabolic tumor volume, total lesion glycolysis) and early response PET/CT (Δ maximum standardized uptake value, Δ peak standardized uptake value corrected for lean body mass), were promising features. CONCLUSION: Both multiparametric MRI and [ 18 F]FDG PET/CT contain promising imaging features to predict response to neoadjuvant chemoradiotherapy in LARC patients. A future larger trial should investigate baseline, early response, and end-of-treatment presurgical evaluation MRI and baseline and early response PET/CT.

Watch and wait after neoadjuvant treatment in rectal cancer: comparison of outcomes in patients with and without a complete response at first reassessment in the International Watch & Wait Database (IWWD).

BACKGROUND: In rectal cancer, watch and wait for patients with a cCR after neoadjuvant treatment has an established evidence base. However, there is a lack of consensus on the definition and management of a near-cCR. This study aimed to compare outcomes in patients who achieved a cCR at first reassessment versus later reassessment. METHODS: This registry study included patients from the International Watch & Wait Database. Patients were categorized as having a cCR at first reassessment or at later reassessment (that is near-cCR at first reassessment) based on MRI and endoscopy. Organ preservation, distant metastasis-free survival, and overall survival rates were calculated. Subgroup analyses were done for near-cCR groups based on the response evaluation according to modality. RESULTS: A total of 1010 patients were identified. At first reassessment, 608 patients had a cCR; 402 had a cCR at later reassessment. Median follow-up was 2.6 years for patients with a cCR at first reassessment and 2.9 years for those with a cCR at later reassessment. The 2-year organ preservation rate was 77.8 (95 per cent c.i. 74.2 to 81.5) and 79.3 (75.1 to 83.7) per cent respectively (P = 0.499). Similarly, no differences were found between groups in distant metastasis-free survival or overall survival rate. Subgroup analyses showed a higher organ preservation rate in the group with a near-cCR categorized exclusively by MRI. CONCLUSION: Oncological outcomes for patients with a cCR at later reassessment are no worse than those of patients with a cCR at first reassessment.

Watch and wait after a clinical complete response in rectal cancer patients younger than 50 years.

BACKGROUND: Young-onset rectal cancer, in patients less than 50 years, is expected to increase in the coming years. A watch-and-wait strategy is nowadays increasingly practised in patients with a clinical complete response (cCR) after neoadjuvant treatment. Nevertheless, there may be reluctance to offer organ preservation treatment to young patients owing to a potentially higher oncological risk. This study compared patients aged less than 50 years with those aged 50 years or more to identify possible differences in oncological outcomes of watch and wait. METHODS: The study analysed data from patients with a cCR after neoadjuvant therapy in whom surgery was omitted, registered in the retrospective-prospective, multicentre International Watch & Wait Database (IWWD). RESULTS: In the IWWD, 1552 patients met the inclusion criteria, of whom 199 (12.8 per cent) were aged less than 50 years. Patients younger than 50 years had a higher T category of disease at diagnosis (P = 0.011). The disease-specific survival rate at 3 years was 98 (95 per cent c.i. 93 to 99) per cent in this group, compared with 97 (95 to 98) per cent in patients aged over 50 years (hazard ratio (HR) 1.67, 95 per cent c.i. 0.76 to 3.64; P = 0.199). The cumulative probability of local regrowth at 3 years was 24 (95 per cent c.i. 18 to 31) per cent in patients less than 50 years and 26 (23 to 29) per cent among those aged 50 years or more (HR 1.09, 0.79 to 1.49; P = 0.603). Both groups had a cumulative probability of distant metastases of 10 per cent at 3 years (HR 1.00, 0.62 to 1.62; P = 0.998). CONCLUSION: There is no additional oncological risk in young patients compared with their older counterparts when following a watch-and-wait strategy after a cCR. In light of a shared decision-making process, watch and wait should be also be discussed with young patients who have a cCR after neoadjuvant treatment.