Rectal cancer patients with a clinical complete response to neoadjuvant (chemo)radiation are eligible for Watch and Wait (W&W). For local regrowth, total mesorectal excision (TME) is considered the standard of care. This study evaluated local excision (LE) for suspected local regrowth. From 591 patients prospectively entered into a national W&W registry, 77 patients with LE for regrowth were included. Outcomes analyzed included histopathologic findings, locoregional recurrence, long-term organ preservation, and colostomy-free and overall survival. In total, 27/77 patients underwent early LE (<6 months after neoadjuvant radiotherapy) and 50/77 underwent late LE (≥6 months). Median follow-up was 53 (39–69) months. In 28/77 patients the LE specimen was histopathologically classified as ypT0 (including 9 adenomas); 11/77 were ypT1, and 38/77 were ypT2–3. After LE, 13/77 patients with ypT2–3 and/or irradical resection underwent completion TME. Subsequently, 14/64 patients without completion TME developed locoregional recurrence, and were successfully treated with salvage TME. Another 8/77 patients developed distant metastases. At 5 years, overall organ preservation was 63%, colostomy-free survival was 68%, and overall survival was 96%. There were no differences in outcomes between early or late LE. In W&W for rectal cancer, LE can be considered as an alternative to TME for suspected regrowth in selected patients who wish to preserve their rectum or avoid colostomy in distal rectal cancer.

Total mesorectal excision for rectal cancer is a major operation associated with morbidity and mortality. For older or inoperable patients, alternatives are necessary. This prospective study evaluated the oncological and functional outcome and quality of life of older or inoperable rectal cancer patients treated with a contact X-ray brachytherapy boost to avoid major surgery. During follow-up, tumor response and toxicity on endoscopy were scored. Functional outcome and quality of life were assessed with self-administered questionnaires. Additionally, in-depth interviews regarding patients’ experiences were conducted. Nineteen patients were included with a median age of 80 years (range 72–91); nine patients achieved a clinical complete response and in another four local control of the tumor was established. The 12 month organ-preservation rate, progression-free survival, and overall survival were 88%, 78%, and 100%, respectively. A transient decrease in quality of life and bowel function was observed at 3 months, which was generally restored at 6 months. In-depth interviews revealed that patients’ experience was positive despite the side-effects shortly after treatment. In older or inoperable rectal cancer patients, contact X-ray brachytherapy can be considered an option to avoid total mesorectal excision. Contact X-ray brachytherapy is well-tolerated and can provide good tumor control.

Introduction Standard treatment for patients with intermediate or locally advanced rectal cancer is (chemo)radiotherapy followed by total mesorectal excision (TME) surgery. In recent years, organ preservation aiming at improving quality of life has been explored. Patients with a complete clinical response to (chemo)radiotherapy can be managed safely with a watch-and-wait approach. However, the optimal organ-preserving treatment strategy for patients with a good, but not complete clinical response remains unclear. The aim of the OPAXX study is to determine the rate of organ preservation that can be achieved in patients with rectal cancer with a good clinical response after neoadjuvant (chemo)radiotherapy by additional local treatment options. Methods and analysis The OPAXX study is a Dutch multicentre study that investigates the efficacy of two additional local treatments aiming at organ preservation in patients with a good, but not complete response to neoadjuvant treatment (ie near-complete response or a small residual tumour mass <3 cm). The sample size will be 168 patients in total. Patients will be randomised (1:1) between two parallel single-arm phase II studies: study arm 1 involves additional contact X-ray brachytherapy (an intraluminal radiation boost), while in study arm 2 the observation period is extended followed by a second response evaluation and optional transanal local excision. The primary endpoint of the study is the rate of successful organ preservation at 1 year following randomisation. Secondary endpoints include toxicity, morbidity, oncological and functional outcomes at 1 and 2 years of follow-up. Finally, an observational cohort study for patients who are not eligible for randomisation is conducted. Ethics and dissemination The trial protocol has been approved by the medical ethics committee of the Netherlands Cancer Institute (METC20.1276/M20PAX). Informed consent will be obtained from all participants. The trial results will be published in an international peer-reviewed journal. Trial registration number NCT05772923.

Pretreatment response prediction is crucial to select those patients with rectal cancer who will benefit from organ preservation strategies following (intensified) neoadjuvant therapy and to avoid unnecessary toxicity in those who will not. The combination of individual predictors in multivariable prediction models might improve predictive accuracy. The aim of this systematic review was to summarize and critically appraise validated pretreatment prediction models (other than radiomics-based models or image-based deep learning models) for response to neoadjuvant therapy in patients with rectal cancer and provide evidence-based recommendations for future research. MEDLINE via Ovid, Embase.com, and Scopus were searched for eligible studies published up to November 2022. A total of 5006 studies were screened and 16 were included for data extraction and risk of bias assessment using Prediction model Risk Of Bias Assessment Tool (PROBAST). All selected models were unique and grouped into five predictor categories: clinical, combined, genetics, metabolites, and pathology. Studies generally included patients with intermediate or advanced tumor stages who were treated with neoadjuvant chemoradiotherapy. Evaluated outcomes were pathological complete response and pathological tumor response. All studies were considered to have a high risk of bias and none of the models were externally validated in an independent study. Discriminative performances, estimated with the area under the curve (AUC), ranged per predictor category from 0.60 to 0.70 (clinical), 0.78 to 0.81 (combined), 0.66 to 0.91 (genetics), 0.54 to 0.80 (metabolites), and 0.71 to 0.91 (pathology). Model calibration outcomes were reported in five studies. Two collagen feature-based models showed the best predictive performance (AUCs 0.83–0.91 and good calibration). In conclusion, some pretreatment models for response prediction in rectal cancer show encouraging predictive potential but, given the high risk of bias in these studies, their value should be evaluated in future, well-designed studies.

BACKGROUND: For nodal regrowth in patients with rectal cancer following watch-and-wait, standardized protocols on diagnostic procedures and subsequent treatment are lacking. OBJECTIVE: To evaluate the diagnosis and treatment of suspected nodal regrowth following an organ preservation approach. SETTINGS: Patients were included from national and institutional watch-and-wait databases. DESIGN: Thirty-five rectal cancer patients with suspected nodal regrowth on MRI were retrospectively identified during watch-and-wait follow-up. PATIENTS: Twenty-seven of 35 patients followed the watch-and-wait schedule after neoadjuvant (chemo)radiotherapy and 8 of 35 patients followed the watch-and-wait schedule after local excision for early rectal cancer. MAIN OUTCOME MEASURES: Diagnostic procedures, treatment, and histopathological outcome. RESULTS: The median follow-up was 34 months. The median time from the end of (chemo)radiotherapy or local excision to the first detection of suspected nodal regrowth on MRI following watch-and-wait was 9 and 10 months. After the first detection, 17 of 35 patients underwent immediate treatment without further diagnostics, of whom 7 also had luminal regrowth. In 18 of 35 patients, additional diagnostic procedures were performed. In 4 of 18 patients, PET-CT or endorectal ultrasound-guided biopsy was performed, and treatment was initiated on the basis of increased nodal regrowth suspicion. In 14 of 18 patients, MRI was repeated after 8 to 12 weeks: growth of suspected lymph nodes was the most decisive factor to proceed to treatment. In 8 patients, repeated MRI was combined with PET-CT and/or endorectal ultrasound-guided biopsy: in half of them, it contributed to treatment initiation. In total, 34 of 35 patients were treated: 9 received (re-)irradiation and 33 underwent total mesorectal excision. In 27 of 33 patients, nodal regrowth was pathologically confirmed in the total mesorectal excision-resection specimen; 5 of 6 patients without nodal involvement had pathologically confirmed luminal regrowth. LIMITATIONS: Highly selected study population. CONCLUSIONS: During watch-and-wait follow-up of patients with rectal cancer in an organ preservation strategy, MRI plays an important role in the diagnosis of nodal regrowth. Repeated MRI after an interval can be helpful in making treatment decisions, and the role of PET-CT and endorectal ultrasound-guided biopsy appears limited. See Video Abstract. ¿QUÉ HACER ANTE LA SOSPECHA DE UN NUEVO CRECIMIENTO GANGLIONAR EN LA RESONANCIA MAGNÉTICA DURANTE EL SEGUIMIENTO EN UN ENFOQUE DE PRESERVACIÓN DE ÓRGANOS PARA EL CÁNCER DE RECTO?: ANTECEDENTES: Para el recrecimiento ganglionar en pacientes con cáncer de recto posterior a watch-and-wait (W&W), faltan protocolos estandarizados de sobre procedimientos de diagnóstico y tratamiento subsecuente. OBJETIVO: Evaluar el diagnóstico y tratamiento de sospecha de recrecimiento ganglionar posterior a tratamiento de preservación del órgano. ENTORNO CLINICO: Se incluyeron pacientes de la base de datos W&W nacionales e institucionales. DISEÑO: Se identificaron retrospectivamente 35 pacientes con cáncer de recto con sospecha de recrecimiento ganglionar en la resonancia magnética durante el seguimiento de W&W. PACIENTES: 27 de 35 pacientes siguieron el programa W&W después de (quimio)radioterapia neoadyuvante y 8 de 35 siguieron el programa W&W después de la escisión local en cáncer rectal temprano. PRINCIPALES MEDIDAS DE RESULTADO: Procedimientos de diagnóstico, tratamiento y resultado histopatológico. RESULTADOS: La mediana de seguimiento fue de 34 meses. La mediana de tiempo desde el final de la (quimio)radioterapia o la escisión local hasta la primera detección de un presunto recrecimiento ganglionar en la resonancia magnética después de W&W fue de 9 y 10 meses. Después de la primera detección, 17 de 35 pacientes fueron sometidos a tratamiento inmediato sin diagnóstico adicional, de los cuales 7 también tuvieron un nuevo crecimiento luminal. En 18 de 35 pacientes se realizaron procedimientos de diagnóstico adicionales. En 4 de 18 pacientes se realizó PET-CT o biopsia guiada por ecografía endorrectal (ERUS) y se inició tratamiento en base a una mayor sospecha de recrecimiento ganglionar. En 14 de 18 pacientes, la resonancia magnética se repitió después de 8 a 12 semanas: el crecimiento de los ganglios linfáticos sospechosos fue el factor más decisivo para proceder al tratamiento. En 8 pacientes, la resonancia magnética repetida se combinó con PET-CT y/o biopsia guiada por ERUS: en la mitad de ellos contribuyó al inicio del tratamiento. En total, se trataron 34 de 35 pacientes: 9 recibieron (re)irradiación y 33 se sometieron a escisión total de mesorrecto. En 27 de 33 pacientes se confirmó patológicamente el recrecimiento ganglionar en la muestra de escisión total de mesorrecto; 5 de 6 pacientes sin afectación ganglionar tuvieron un recrecimiento luminal patológicamente confirmado. LIMITACIONES: Población de estudio altamente seleccionada. CONCLUSIONES: Durante el seguimiento de W&W de pacientes con cáncer de recto en estrategia de preservación de órganos, la resonancia magnética juega un papel importante en el diagnóstico del recrecimiento ganglionar. La repetición de la resonancia magnética después de un intervalo puede ser útil para tomar decisiones de tratamiento, y el papel de la PET-CT y la biopsia guiada por ERUS parece limitado. (Traducción— Dr. Francisco M. Abarca-Rendon)

4528 Background: Successful platinum(Pt)-based chemotherapy for testicular cancer (TC) comes at the price of late cardiovascular morbidity and neurotoxicity. Damage induced by circulating Pt could be an etiological mechanism. We investigated the relation between circulating Pt and late effects. Methods: In 96 consecutive TC patients (med age 29 [17-53] at chemotherapy), 3 serum samples and a 24h-urine sample were collected on several time-points med 5 yrs (1-13) after treatment. Pt concentrations ([Pt]) were measured with a sensitive voltammetric method (Lancet 2000, 355:1075). Measured [Pt] combined with cisplatin dose, age, weight and height were analyzed simultaneously to construct a population pharmacokinetic (PK) model using NONMEM. Based on the PK parameters of each patient, individual [Pt] at 1, 3, 5, 10 yrs after start and AUC were calculated. Cardiovascular status, paresthesia and markers of vascular damage were assessed after a med follow-up (FU) of 9 yrs (3-15). Results: Decay of [Pt] was best described by a two compartment model. Mean terminal T_1/2 was 3.7 (±0.3) yrs. At all time-points [Pt] correlated with cisplatin dose and renal function during treatment. [Pt] at 3 yrs correlated with systolic blood pressure (BP) (r=.32, p<0.01) and creatinine clearance (CRCL) (r=-.25, p=0.02) at FU. Patients with increased BP had higher Pt AUCs than patients with normal BP (table). Pt AUCs were higher in patients with paresthesia (table). Conclusions: Known late effects of cisplatin-based chemotherapy such as hypertension and paresthesia are related to higher circulating [Pt]. Long-term exposure to Pt is involved in healthy tissue damage in TC survivors. [Table: see text]