Multivariable prognostic modelling to improve prediction of colorectal cancer recurrence: the PROSPeCT trial.

OBJECTIVE: Improving prognostication to direct personalised therapy remains an unmet need. This study prospectively investigated promising CT, genetic, and immunohistochemical markers to improve the prediction of colorectal cancer recurrence. MATERIAL AND METHODS: This multicentre trial (ISRCTN 95037515) recruited patients with primary colorectal cancer undergoing CT staging from 13 hospitals. Follow-up identified cancer recurrence and death. A baseline model for cancer recurrence at 3 years was developed from pre-specified clinicopathological variables (age, sex, tumour-node stage, tumour size, location, extramural venous invasion, and treatment). Then, CT perfusion (blood flow, blood volume, transit time and permeability), genetic (RAS, RAF, and DNA mismatch repair), and immunohistochemical markers of angiogenesis and hypoxia (CD105, vascular endothelial growth factor, glucose transporter protein, and hypoxia-inducible factor) were added to assess whether prediction improved over tumour-node staging alone as the main outcome measure. RESULTS: Three hundred twenty-six of 448 participants formed the final cohort (226 male; mean 66 ± 10 years. 227 (70%) had ≥ T3 stage cancers; 151 (46%) were node-positive; 81 (25%) developed subsequent recurrence. The sensitivity and specificity of staging alone for recurrence were 0.56 [95% CI: 0.44, 0.67] and 0.58 [0.51, 0.64], respectively. The baseline clinicopathologic model improved specificity (0.74 [0.68, 0.79], with equivalent sensitivity of 0.57 [0.45, 0.68] for high vs medium/low-risk participants. The addition of prespecified CT perfusion, genetic, and immunohistochemical markers did not improve prediction over and above the clinicopathologic model (sensitivity, 0.58-0.68; specificity, 0.75-0.76). CONCLUSION: A multivariable clinicopathological model outperformed staging in identifying patients at high risk of recurrence. Promising CT, genetic, and immunohistochemical markers investigated did not further improve prognostication in rigorous prospective evaluation. CLINICAL RELEVANCE STATEMENT: A prognostic model based on clinicopathological variables including age, sex, tumour-node stage, size, location, and extramural venous invasion better identifies colorectal cancer patients at high risk of recurrence for neoadjuvant/adjuvant therapy than stage alone. KEY POINTS: Identification of colorectal cancer patients at high risk of recurrence is an unmet need for treatment personalisation. This model for recurrence, incorporating many patient variables, had higher specificity than staging alone. Continued optimisation of risk stratification schema will help individualise treatment plans and follow-up schedules.

Robotic transanal minimally invasive surgery (r-TAMIS): perioperative and short-term outcomes for local excision of rectal cancers.

BACKGROUND: Transanal minimally invasive surgery (TAMIS) is an advanced technique for excision of early rectal cancers. Robotic TAMIS (r-TAMIS) has been introduced as technical improvement and potential alternative to total mesorectal excision (TME) in early rectal cancers and in frail patients. This study reports the perioperative and short-term oncological outcomes of r-TAMIS for local excision of early-stage rectal cancers. METHODS: Retrospective analysis of a prospectively collected r-TAMIS database (July 2021-July 2023). Demographics, clinicopathological features, short-term outcomes, recurrences, and survival were investigated. RESULTS: Twenty patients were included. Median age and body mass index were 69.5 (62.0-77.7) years and 31.0 (21.0-36.5) kg/m2. Male sex was prevalent (n = 12, 60.0%). ASA III accounted for 66.7%. Median distance from anal verge was 7.5 (5.0-11.7) cm. Median operation time was 90.0 (60.0-112.5) minutes. Blood loss was minimal. There were no conversions. Median postoperative stay was 2.0 (1.0-3.0) days. Minor and major complication rates were 25.0% and 0%, respectively. Seventeen (85.0%) patients had an adenocarcinoma whilst three patients had an adenoma. R0 rate was 90.0%. Most tumours were pT1 (55.0%), followed by pT2 (25.0%). One patient (5.0%) had a pT3 tumour. Specimen and tumour maximal median diameter were 51.0 (41.0-62.0) mm and 21.5 (17.2-42.0) mm, respectively. Median specimen area was 193.1 (134.3-323.3) cm2. Median follow-up was 15.5 (10.0-24.0) months. One patient developed local recurrence (5.0%). CONCLUSIONS: r-TAMIS, with strict postoperative surveillance, is a safe and feasible approach for local excision of early rectal cancer and may have a role in surgically unfit and elderly patients who refuse or cannot undergo TME surgery. Future prospective multicentre large-scale studies are needed to report the long-term oncological outcomes.

Influence of diffusion weighted imaging and contrast enhanced T1 sequences on the diagnostic accuracy of magnetic resonance enterography for Crohn's disease.

OBJECTIVES: To evaluate the additional diagnostic benefit of diffusion weighted imaging (DWI) and contrast enhanced (CE) images during MR enterography (MRE) of Crohn's disease. METHODS: Datasets from 73 patients (mean age 32; 40 male) (28 new-diagnosis, 45 relapsed) were read independently by two radiologists selected from a pool of 13. Radiologists interpreted datasets using three sequential sequence blocks: (1) T2 weighted and steady state free precession gradient echo (SSFP) images alone (T2^); (2) T2 weighted and SSFP images with DWI (T2 + DWI^) and; (3) T2 weighted images, SSFP, DWI and post-contrast enhanced (CE) T1 images (T2 + DWI + CE^), documenting presence, location, and activity of small bowel disease. For each sequence block, sensitivity and specificity (readers combined) was calculated against an outcome-based construct reference standard. RESULTS: 59/73 patients had small bowel disease. Per-patient sensitivity for disease detection was essentially identical (80 % [95 % CI 72, 86], 81 % [73,87], and 79 % [71,86] for T2^, T2 + DWI^and T2 + DWI + CE^respectively). Specificity was identical (82 % [64 to 92]). Per patient sensitivity for disease extent was 56 % (47,65), 56 % (47,65) and 52 % (43 to 61) respectively, and specificity was 82 % (64 to 92) for all blocks. Sensitivity for active disease was 97 % (90,99), 97 % (90,99) and 98 % (92,99), and specificity was also comparable between all sequence combination reads. Results were consistent across segments and newly diagnosed/relapse patients. CONCLUSION: There is no additional diagnostic benefit of adding either DWI or CE to T2 FSE and SSFP sequences for evaluating small bowel Crohn's disease, suggesting MRE protocols can be simplified safely.