October 2025

This study is a phase III non-inferior randomized clinical trial involving 17 hospitals within Spain, exploring whether neoadjuvant chemoradiotherapy and trans-anal endoscopic excision in T2 or T3 rectal cancers lead to similar clinical outcomes compared to the standard of care. The authors found, in the 5-year modified intention-to-treat analysis, there were no differences in local recurrence, and similar results for distant recurrence and overall survival rates.

Summary: International guidelines recommend total mesorectal excision (TME) as the standard treatment for T2 and early T3 (T3ab), N0, M0 rectal cancer. T3ab tumors are those that penetrate the muscularis propria but with invasion ≤ 5mm without nodal involvement or distal metastases. Local excision is generally not recommended, especially for T3 tumors, due to the risk of regional lymph node involvement. In this setting, TME is typically performed as the oncologic resection, but carries with it a risk of complications as high as 54%, in large part due to the likely need for diverting stoma creation and associated risks. An alternative strategy is neoadjuvant chemoradiotherapy with local excision, with single-center observational studies having published clinical data with inconclusive results. The purpose of this study was to compare standard treatment of stage T2-T3ab, N0, M0 by TME vs. long-course chemoradiotherapy followed by local excision via transanal endoscopic microsurgery (TEM).

The study design was an open-label, prospective, non-inferiority trial at 17 hospitals within Spain. Patients were included if they had a diagnosis of a rectal adenocarcinoma located 10 cm from the anal verge, clinical stage T2-T3ab, N0, M0 confirmed by endorectal ultrasound and rectal MRI, tumors with maximum diameter of 4 cm or less on MRI, and ASA stage 3 or less. Exclusion criteria included presence of distant metastases, synchronous colorectal cancers, undifferentiated rectal adenocarcinomas, or intolerance of chemotherapy or radiotherapy. Treatment in the TEM group received long-course neoadjuvant treatment with combined chemotherapy and radiotherapy (oral capecitabine and daily fractions of 1.8 Gy, 5 days a week). Clinical response was assessed using rectal MRI. Surgery was performed in the eighth week after CRT. Local excision was performed with TEM or transanal minimally invasive surgery (TAMIS) by a colorectal surgeon. The protocol was discontinued in patients who showed no clinical response after CRT and in those whose pathology after excision showed characteristics of poor prognosis. The primary outcome was local recurrence (LR), defined as the presence of adenocarcinoma in the biopsy of the residual scar, anastomosis, tumor resection bed, locoregional pelvic lymphadenopathy, or in the perineal skin after abdominoperineal resection. Secondary outcomes included distal recurrence (DR), overall survival (OS) and disease free survival (DFS).

From 2010 to 2021, 364 patients were evaluated for inclusion with 173 ultimately randomized into the study; 81 patients were included in each group for the modified intention to treat (mITT) analysis. The median follow-up time for mITT and per protocol (PP) analysis was 63 months. Post operative morbidity was 20.7% in the TEM group and 50.6% in the TME group. In the 5-year mITT analysis, LR was 7.4% in the CRT-TEM group and 6.2% in the TME group (difference -1.23%, p=0.76). In the TME group, 17 patients had nodal involvement and underwent adjuvant treatment; of these 41.2% developed distant recurrence versus 10.9% of those with node-negative status. In the mITT analysis, CRT-TEM had a DR of 12.3% versus 17.3% in the TME group (difference 4.94%, CI 15.85% to -5.98%). In the 5-year mITT analysis, the OS was 82.7% for the CRT-TEM group versus 85.2% in the TME group (p=0.62). The DFS was the same in the 2 groups at 88.9%.

Strengths of the study include a notable reduction in the incidence of occult nodal involvement of the TEM group with neoadjuvant treatment (approximately 15% reduction) and good long-term results obtained in the TME control group for the secondary outcomes. Limitations include the long duration of the study, in which changes in diagnostic and treatment modalities may have occurred. Lastly, the study was not formally powered to detect differences between groups on secondary outcomes.

Bottom Line: A Spanish multicenter non-inferiority randomized clinical trial comparing TME (standard treatment) with neoadjuvant chemoradiation with trans-anal endoscopic microsurgical (TEM) excision strategy for T2 or T3ab (confined to ≤ 5mm outside muscularis propria) rectal cancer treatment demonstrated non-inferior local recurrence rates with similar distant recurrence and overall survival. A less invasive approach sparing the rectum with chemoradiation followed by trans-anal endoscopic excision may be suitable for these tumors, allowing patients a less morbid alternative to TME. 

This multi-center European and Asian retrospective cohort study evaluated the prognostic significance of positive peritoneal cytology (POPEC) in patients with gastric cancer who had no radiologic or macroscopic evidence of metastatic disease. The investigators found that while positive cytology correlated with higher tumor stage, it was not independently associated with poorer 5-year overall survival after adjustment for pathologic stage and receipt of neoadjuvant therapy. The study also demonstrated substantial variability in cytology sampling techniques across centers, which affected the detection rate of positive cytology. These findings suggest that positive peritoneal cytology alone should not preclude curative-intent surgery but underscore the need for standardized cytologic sampling protocols and prospective validation.

Summary: The POPEC study was a large, multi-institutional retrospective cohort analysis conducted across 16 European and Asian tertiary gastric cancer centers. The study population included 837 adult patients with histologically confirmed gastric adenocarcinoma who underwent staging laparoscopy with peritoneal lavage cytology prior to curative-intent gastrectomy between 2009 and 2023. Patients with radiologic or macroscopic peritoneal metastases (M1 disease) were excluded. The primary objective was to assess the prognostic impact of positive peritoneal cytology on overall survival in patients without overt metastatic disease.

Among the 837 included patients, the median age was 66 years, and 71% were male. Non-distal gastric cancer was most common (47 %), and the majority of tumors were advanced at diagnosis, with 59% staged as pT3–4 and 43% as pN2–3. Positive peritoneal cytology was detected in 66 patients (7.9%). Those with positive cytology (CY⁺) tended to have more advanced T and N stages, consistent with greater disease burden. Patients with CY⁺ disease had a median overall survival of 37 months and not reached for CY⁻ patients (p = 0.06). After multivariable adjustment for confounders—including pathological stage, tumor location, and administration of neoadjuvant therapy—positive cytology was not independently associated with worse 5-year overall survival (HR 1.06, 95% CI 0.61–1.8).

The study also identified significant heterogeneity in cytology sampling techniques across institutions. Specifically, the number of peritoneal quadrants sampled and the lavage methods varied, and while there was no clear trend, there was an association with overall survival. Centers that sampled multiple quadrants detected a higher proportion of positive cytology cases, suggesting that under-sampling may lead to underestimation of true disease burden.

Key limitations included the retrospective nature of the study, which introduces potential for selection bias, and the relatively small number of cytology-positive patients, limiting statistical power for subgroup analyses. The lack of standardization in peritoneal lavage technique across centers further complicates interpretation of the results, and long-term outcomes beyond five years were not evaluated.

Bottom Line: In this large multi-center European and Asian cohort, positive peritoneal cytology in patients with gastric cancer without macroscopic metastases was not independently predictive of worse 5-year overall survival after adjustment for tumor stage and treatment factors. These findings challenge the conventional view that cytology-positive status should automatically exclude patients from curative surgical intervention. Instead, they highlight the importance of integrating cytology results with other clinical and pathological factors when determining surgical eligibility. 

This randomized control trial studied the impact of violence, arrests, and death among individuals participating in a community-researcher partnership, Rapid Employment and Development Initiative (READI) Chicago. The trial enrolled nearly 2500 individuals and showed evidence of reduced shooting and homicide arrests in the READI arm compared to controls. Additionally, there was an estimated $182,000 to $916,000 per participant social costs savings.

Summary: This study is a randomized controlled trial of a Chicago-based community violence intervention, Rapid Employment and Development Initiative (READI). READI works in 5 Chicago neighborhoods with the highest rates of violence and offers high risk individuals an 18-month subsidized employment program along with cognitive behavioral therapy. High risk individuals were identified based on a machine learning algorithm with 3 components: administrative arrests and victimization records, referrals from local outreach workers and screening among individuals leaving prison and jail. 2,456 participants in the study were randomized to either participate in READI or a control group that was free to pursue other community-based services. The primary outcome was violent crime associated events, which was measured by shooting and homicide victimization, arrest or other serious violent crime arrests, such as robbery or battery.

For every 100 people in the control group, there were 11 shootings and homicide victimizations among the intervention group. There were no statistically significant differences between groups for the primary outcome, across all three violent crime categories. There was however a 65% relative reduction in suicide and homicide related arrests, though this was not statistically significant. Additionally, participants who were referred to READI by outreach workers (e.g. HVIP specialists), had the greatest decrease in serious violent involvement compared to matched controls (79 vs 43%). The authors estimated cost savings between $182,000 and $916,000 per participant, and a benefit to cost ratio of READI to be between 4:1 and 18:1.

Hospital-based and community-based violence intervention programming often provide individualized services, leading to immense heterogeneity and presenting a challenge to evaluating efficacy. The authors provide a robust study of a community-based violence intervention program, highlighting the challenges in their evaluation. While the authors show no difference in their primary outcome with READI participation, they do demonstrate benefit. This study demonstrates the intensive, multipronged community-based programming that addresses upstream social determinants of health is feasible and cost-effective. It also highlights the positive impact outreach workers, such as HVIP specialists, have on outcomes for survivors of violent injury, noting a reduction in serious violent crime.

Bottom line: Targeted, multi-pronged, and coordinated violence intervention programming, is both feasible and cost-effective and can reduce recurrent involvement in violence.