Validated Pretreatment Prediction Models for Response to Neoadjuvant Therapy in Patients with Rectal Cancer: A Systematic Review and Critical Appraisal.

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.

New Opportunities for Minimizing Toxicity in Rectal Cancer Management.

Advances in multimodal management of locally advanced rectal cancer (LARC), consisting of preoperative chemotherapy and/or radiotherapy followed by surgery with or without adjuvant chemotherapy, have improved local disease control and patient survival but are associated with significant risk for acute and long-term morbidity. Recently published trials, evaluating treatment dose intensification via the addition of preoperative induction or consolidation chemotherapy (total neoadjuvant therapy [TNT]), have demonstrated improved tumor response rates while maintaining acceptable toxicity. In addition, TNT has led to an increased number of patients achieving a clinical complete response and thus eligible to pursue a nonoperative, organ-preserving, watch and wait approach, thereby avoiding toxicities associated with surgery, such as bowel dysfunction and stoma-related complications. Ongoing trials using immune checkpoint inhibitors in patients with mismatch repair-deficient tumors suggest that this subgroup of patients with LARC could potentially be treated with immunotherapy alone, sparing them the toxicity associated with preoperative treatment and surgery. However, the majority of rectal cancers are mismatch repair-proficient and less responsive to immune checkpoint inhibitors and require multimodal management. The synergy noted in preclinical studies between immunotherapy and radiotherapy on immunogenic tumor cell death has led to the design of ongoing clinical trials that explore the benefit of combining radiotherapy, chemotherapy, and immunotherapy (mainly of immune checkpoint inhibitors) and aim to increase the number of patients eligible for organ preservation.

Lateral Lymph Nodes in Rectal Cancer: Do we all Think the Same? A Review of Multidisciplinary Obstacles and Treatment Recommendations.

Lateral lymph nodes in low, locally advanced, rectal cancer have proven implications for local recurrence rates, which increase drastically in the presence of persistently enlarged lateral lymph nodes. These clinical implications warrant a thorough understanding of lateral nodal disease with awareness and knowledge from all three specialties involved - radiology, radiation oncology, and surgery - to ensure proper treatment. Relevant literature for each specialty, including all current guidelines and perspectives, were examined. Variations in definitions and treatment paradigms were evaluated. There is still no consensus for the standardized treatment of lateral nodal disease. Each discipline works according to their own available evidence, but relevant data are scarce. Current international guidelines and standard recommendations for the diagnostics and treatment of lateral lymph nodes are lacking. This results in differing perspectives and interpretations between the disciplines which can lead to challenging communication in an area where multidisciplinary collaboration is essential. This review addresses this by presenting the current evidence, perspectives and practices of each specialty and makes suggestions for each phase of the diagnostic and treatment process for patients with lateral nodal disease. By doing this, steps are taken toward achieving international consensus, and multidisciplinary collaboration.

Impact of Dose-Escalated Chemoradiation on Quality of Life in Patients With Locally Advanced Rectal Cancer: 2-Year Follow-Up of the Randomized RECTAL-BOOST Trial.

PURPOSE: Dose-escalated chemoradiation (CRT) for locally advanced rectal cancer did not result in higher complete response rates but initiated more tumor regression in the randomized RECTAL-BOOST trial (Clinicaltrials.gov NCT01951521). This study compared patient reported outcomes between patients who received dose-escalated CRT (5 × 3 gray boost + CRT) or standard CRT for 2 years after randomization. METHODS AND MATERIALS: Patients with locally advanced rectal cancer who were participating in the RECTAL-BOOST trial filled out European Organisation for Research and Treatment of Cancer QLQ-C30 and CR29 questionnaires on quality of life (QoL) and symptoms at baseline, 3, 6, 12, 18, and 24 months after start of treatment. Between-group differences in functional QoL domains were estimated using a linear mixed-effects model and expressed as effect size (ES). Symptom scores were compared using Mann-Whitney U test. RESULTS: Patients treated with dose-escalated CRT (boost group, n = 51) experienced a significantly stronger decline in global health at 3 and 6 months (ES -0.4 and ES -0.4), physical functioning at 6 months (ES -1.1), role functioning at 3 and 6 months (ES -0.8 and ES -0.6), and social functioning at 6 months (ES -0.6), compared with patients treated with standard CRT (control group, n = 64). The boost group reported significantly more fatigue at 3 and 6 months (83% vs 66% respectively 89% vs 76%), pain at 3 and 6 months (67% vs 36% respectively 80% vs 44%), and diarrhea at 3 months (45% vs 29%) compared with the control group. From 12 months onwards, QoL and symptoms were similar between groups, apart from more blood/mucus in stool in the boost group. CONCLUSIONS: In patients with locally advanced rectal cancer, dose-escalated CRT resulted in a transient deterioration in global health, physical, role, and social functioning and more pain, fatigue and diarrhea at 3 and 6 months after start of treatment compared with standard CRT. From 12 months onwards, the effect of dose-escalated CRT on QoL largely resolved.

Efficacy of Dose-Escalated Chemoradiation on Complete Tumor Response in Patients with Locally Advanced Rectal Cancer (RECTAL-BOOST): A Phase 2 Randomized Controlled Trial.

PURPOSE: Pathologic complete tumor response after chemoradiation in patients with locally advanced rectal cancer (LARC) is associated with a favorable prognosis and allows organ-sparing treatment strategies. In the RECTAL-BOOST trial, we aimed to investigate the effect of an external radiation boost to the tumor before chemoradiation on pathologic or sustained clinical complete tumor response in LARC. METHODS AND MATERIALS: This multicenter, nonblinded, phase 2 randomized controlled trial followed the trials-within-cohorts design, which is a pragmatic trial design allowing cohort participants to be randomized for an experimental intervention. Patients in the intervention group are offered the intervention (and can either accept or refuse this), whereas patients in the control group are not notified about the randomization. Participants of a colorectal cancer cohort referred for chemoradiation of LARC to either of 2 radiation therapy centers were eligible. Patients were randomized to no boost or an external radiation boost (5 × 3 Gy) without concurrent chemotherapy, directly followed by standard pelvic chemoradiation (25 × 2 Gy with concurrent capecitabine). The primary outcome was pathologic complete response (ie, ypT0N0) in patients with planned surgery at 12 weeks, or, as surrogate for pathologic complete response, a 2-year sustained clinical complete response for patients treated with an organ preservation strategy. Analyses were intention to treat. The study was registered with ClinicalTrials.gov, number NCT01951521. RESULTS: Between September 2014 and July 2018, 128 patients were randomized. Fifty-one of the 64 (79.7%) patients in the intervention group accepted and received a boost. Compared with the control group, fewer patients in the intervention group had a cT4 stage and a low rectal tumor (31.3% vs 17.2% and 56.3% vs 45.3%, respectively), and more patients had a cN2 stage (59.4% vs 70.3%, respectively). Rate of pathologic or sustained clinical complete tumor response was similar between the groups: 23 of 64 (35.9%; 95% confidence interval [CI], 24.3-48.9) in the intervention group versus 24 of 64 (37.5%; 95% CI, 25.7-50.5) in the control group (odds ratio [OR] = 0.94; 95% CI, 0.46-1.92). Near-complete or complete tumor regression was more common in the intervention group (34 of 49; 69.4%) than in the control group (24 of 53; 45.3%; (OR = 2.74, 95% CI 1.21-6.18). Grade ≥3 acute toxicity was comparable: 6 of 64 (9.4%) in the intervention group versus 5 of 64 (7.8%) in the control group (OR = 1.22; 95% CI, 0.35-4.22). CONCLUSIONS: Dose escalation with an external radiation therapy boost to the tumor before neoadjuvant chemoradiation did not increase the pathologic or sustained clinical complete tumor response rate in LARC.

Patient-Reported Work Ability During the First Two Years After Rectal Cancer Diagnosis.

BACKGROUND: Rectal cancer treatment is associated with substantial short- and longer-term morbidity that may affect patients' ability to work. OBJECTIVE: We evaluated patient-reported work ability during the first 2 years after rectal cancer diagnosis, relative to the Dutch general population. Also, we assessed the association between clinical factors and work ability. DESIGN: This is a prospective cohort study. SETTINGS: This study was conducted at the Radiation-Oncology Department of a tertiary center. PATIENTS: Patients with rectal cancer, <67 years of age, and treated with curative intent were selected. MAIN OUTCOME MEASURES: Work ability was assessed with the Work Ability Index before the start of treatment (baseline) and at 3, 6, 12, 18, and 24 months after. The Work Ability Index scores of patients with paid employment were compared with the scores of matched population controls. Mixed models were used to estimate the impact of clinical factors on work ability. RESULTS: Of the 230 eligible patients, 172 (75%) had paid employment. Work ability decreased at 3 and 6 months compared with baseline. At 12 months, work ability recovered to baseline level but remained significantly lower than in population controls up to 24 months. Fifty-four percent reported 100 to 365 days of sick leave during the first 12 months of treatment versus 2% in the general population. At 24 months, 32% needed substantial adaptations in work activities, worked reduced hours, or were unable to work due to the disease versus 6% in the general population. Female sex, multiple comorbidities, oligometastatic disease, chemoradiation, and abdominoperineal resection were associated with lower work ability. LIMITATIONS: The study was limited by a decrease in questionnaire response rate from 83% to 64% over time. CONCLUSIONS: Patient-reported work ability deteriorates during rectal cancer treatment. Within 24 months after diagnosis, work ability returns to pretreatment level but remains lower than that of the general population. See Video Abstract at http://links.lww.com/DCR/B175. CAPACIDAD DE TRABAJO REPORTADO POR PACIENTES DURANTE LOS PRIMEROS DOS AÑOS DESPUÉS DEL DIAGNÓSTICO DE CÁNCER RECTAL: El tratamiento del cáncer rectal se asocia con una morbilidad significante a corto y largo plazo que puede afectar la capacidad de trabajo de pacientes.Evaluamos la capacidad de trabajo reportado por pacientes durante los primeros dos años después del diagnóstico de cáncer rectal, en relación con la población general holandesa. Además, evaluamos la asociación entre los factores clínicos y capacidad para trabajar.Estudio de cohorte prospectivo.Este estudio se realizó en el Departamento de Radiación Oncológica de en un centro de referencia de tercer nivel.Se seleccionaron pacientes con cáncer rectal, <67 años de edad, y tratados con intención curativa.La capacidad de trabajo se evaluó con el índice de capacidad de trabajo antes del inicio del tratamiento (línea de base) y a los 3, 6, 12, 18 y 24 meses después. Los puntajes de capacidad laboral de los pacientes con empleo remunerado se compararon con los puntajes de los controles de población pareados. Se utilizaron modelos mixtos para estimar el impacto de los factores clínicos en la capacidad laboral.De los 230 pacientes elegibles, 172 (75%) tenían empleo remunerado. La capacidad de trabajo disminuyó a los 3 y 6 meses en comparación con la línea de base. A los 12 meses, la capacidad de trabajo se recuperó al nivel de referencia, pero se mantuvo significativamente más baja que en los controles de la población hasta 24 meses. Durante los primeros 12 meses, el 54% reportó 100-365 días de baja por enfermedad versus el 2% en la población general. A los 24 meses, el 32% necesitaba adaptaciones sustanciales en las actividades laborales, trabajó horas reducidas o no pudo trabajar debido a la enfermedad frente al 6% en la población general. El sexo femenino, las comorbilidades múltiples, la enfermedad oligometastásica, la quimiorradiación y la resección abdominoperineal se asociaron con una menor capacidad de trabajo.El estudio estuvo limitado por una disminución en la tasa de respuesta al cuestionario del 83% al 64% a lo largo plazo.La capacidad laboral informada por el paciente se deteriora durante el tratamiento del cáncer rectal. Dentro de los 24 meses posteriores al diagnóstico, la capacidad laboral vuelve al nivel de pretratamiento, pero sigue siendo inferior a la de la población general. Consulte Video Resumen en http://links.lww.com/DCR/B175. (Traducción-Dr. Adrian Ortega).

The trials within cohorts design facilitated efficient patient enrollment and generalizability in oncology setting.

OBJECTIVES: The trials within cohorts (TwiCs) design aims to improve recruitment efficiency. We conducted the first TwiCs in radiation oncology and described efficiency of the design and generalizability of the results. STUDY DESIGN AND SETTING: In two radiotherapy centers, patients with rectal cancer were asked to participate in a prospective cohort study and to provide broad consent for randomization and patient-reported outcomes (PROs). Consenting patients who met the trial criteria were randomized directly after cohort enrollment. The intervention arm was offered a radiotherapy boost. We evaluated acceptance rate, its impact on sample size, and compared clinical characteristics between trial participants and patients of the Dutch national cancer registry. RESULTS: 128 of the 200 eligible patients (64%) were randomized. Sixty-two patients did not consent (in time) to cohort participation, to broad randomization, or to PROs. Of the 64 patients in the intervention arm, 52 (81%) accepted the intervention. During the trial, the acceptance rate dropped temporarily, after which sample size was adapted. Trial patients were comparable in age, comorbidity, and disease stage to the national rectal cancer population. CONCLUSIONS: The TwiCs design is feasible, allows enrollment of a high proportion of randomizable patients, with positive impact on trial efficiency and generalizability of results in a clinical oncology setting.

The effect of time interval from chemoradiation to surgery on postoperative complications in patients with rectal cancer.

BACKGROUND: A prolonged time interval between chemoradiation and total mesorectal excision (TME) may render more rectal cancer patients eligible for organ-sparing approaches but may also cause more pelvic fibrosis and surgical morbidity. We estimated the effect of time interval on postoperative complications and other surgical outcomes in rectal cancer patients. METHODS: This is a population-based cohort study using data of the Dutch Colorectal Audit. Rectal cancer patients treated with chemoradiation followed by TME after an interval of 3-20 weeks were selected (n = 6,268). Time interval from completion of chemoradiation to TME was categorized into 3-6, 7-8, 9-10, 11-12 and 13-20 weeks. Outcomes included postoperative complication (any, and stratified by medical and surgical complications), reintervention, intraoperative complication, incomplete resection, positive circumferential margin (CRM) and pathological complete response (pCR). The interval of 7-8 weeks was the reference group. RESULTS: Prolonged time intervals were not associated with a higher risk of a postoperative complication (any, surgical or medical), reintervention, and incomplete resection. Intraoperative complications were however more common after 11-12 weeks than after 7-8 weeks (odds ratio (OR) = 1.79, 95% confidence interval (CI) = 1.20-2.69). The interval of 9-10 weeks was associated with less CRM positive resections, and 9-10 and 13-20 weeks with more pCR (relative to 7-8 weeks, OR = 0.74, 95%CI = 0.56-0.98; OR = 1.28, 95%CI = 1.04-1.58; and OR = 1.33, 95%CI = 1.04-1.71, respectively). CONCLUSIONS: Compared with 7-8 weeks, longer time intervals up to 13-20 weeks between chemoradiation and TME are not associated with more postoperative complications or more positive resection margins. Accordingly, prolonging the interval aiming for organ-sparing treatment is safe.

Health-related quality of life in rectal cancer patients undergoing neoadjuvant chemoradiation with delayed surgery versus short-course radiotherapy with immediate surgery: a propensity score-matched cohort study.

BACKGROUND: Neoadjuvant chemoradiation with delayed surgery (CRT-DS) and short-course radiotherapy with immediate surgery (SCRT-IS) are two commonly used treatment strategies for rectal cancer. However, the optimal treatment strategy for patients with intermediate-risk rectal cancer remains a discussion. This study compares quality of life (QOL) between SCRT-IS and CRT-DS from diagnosis until 24 months after treatment. METHODS: In a prospective colorectal cancer cohort, rectal cancer patients with clinical stage T2-3N0-2M0 undergoing SCRT-IS or CRT-DS between 2013 and 2017 were identified. QOL was assessed using EORTC-C30 and EORTC-CR29 questionnaires before the start of neoadjuvant treatment (baseline) and at 3, 6, 12, 18 and 24 months after. Patients were 1:1 matched using propensity sore matching. Between- and within-group differences in QOL domains were analyzed with linear mixed-effects models. Symptoms and sexual interest at 12 and 24 months were compared using logistic regression models. RESULTS: 156 of 225 patients (69%) remained after matching. The CRT-DS group reported poorer emotional functioning at 3, 6, 12, 18 and 24 months (mean difference with SCRT-IS: -9.4, -12.1, -7.3, -8.0 and -7.9 respectively), and poorer global health, physical-, role-, social- and cognitive functioning at 6 months (mean difference with SCRT-IS: -9.1, -9.8, -14.0, -9.2 and -12.6, respectively). Besides emotional functioning, all QOL domains were comparable at 12, 18 and 24 months. Within-group changes showed a significant improvement of emotional functioning after baseline in the SCRT-IS group, whereas only a minor improvement was observed in the CRT-DS group. Symptoms and sexual interest in male patients at 12 and 24 months were comparable between the groups. CONCLUSIONS: In rectal cancer patients, CRT-DS may induce a stronger decline in short-term QOL than SCRT-IS. From 12 months onwards, QOL domains, symptoms and sexual interest in male patients were comparable between the groups. However, emotional functioning remained higher after SCRT-IS than after CRT-DS.

Effect of Neoadjuvant Therapy and Rectal Surgery on Health-related Quality of Life in Patients With Rectal Cancer During the First 2 Years After Diagnosis.

INTRODUCTION: Rectal cancer surgery with neoadjuvant therapy is associated with substantial morbidity. The present study describes the course of quality of life (QOL) in rectal cancer patients in the first 2 years after the start of treatment. PATIENTS AND METHODS: We performed a prospective study within a colorectal cancer cohort including rectal cancer patients who were referred for neoadjuvant chemoradiation or short-course radiotherapy and underwent rectal surgery. QOL was assessed using the European Organization for Research and Treatment of Cancer core questionnaire (EORTC QLQ-C30) and colorectal cancer questionnaire (EORTC QLQ-CR29) before treatment and after 3, 6, 12, 18, and 24 months. The outcomes were compared with the QOL scores from the Dutch general population and stratified by low anterior resection and abdominoperineal resection. Postoperative bowel dysfunction after low anterior resection was measured using the low anterior resection syndrome score. RESULTS: Of the 324 patients, 272 (84%) responded to at least 2 questionnaires and were included in the present study. Compared with pretreatment levels, the strongest decline was observed in physical, role, and social functioning at 3 and 6 months after the start of treatment. Global health and cognitive functioning declined to a lesser extend, and emotional functioning gradually improved over the time. Within 24 months, the QOL scores had recovered toward the pretreatment levels in most patients. Compared with the general population, physical, role, social, and cognitive functioning and symptoms of fatigue and insomnia remained significantly worse in patients on longer-term. After low anterior resection, major bowel dysfunction was reported by 44% to 60% of the patients. Increasing urinary incontinence and severe complaints of impotence were observed in patients who had undergone abdominoperineal resection. CONCLUSION: Rectal cancer treatment is associated with a significant decline in QOL during the first 6 months after the diagnosis. Within 2 years, most patients return toward pretreatment functioning but could still experience poorer functioning and treatment-related symptoms compared with the general population. These findings support shared decision-making and emphasize the need for postoperative supportive care and novel treatment approaches.

Comparison of pathological complete response rates after neoadjuvant short-course radiotherapy or chemoradiation followed by delayed surgery in locally advanced rectal cancer.

INTRODUCTION: Patients with locally advanced rectal cancer (LARC) who are unfit for chemoradiation (CRT), are often offered short-course radiotherapy followed by delayed surgery (SCRT-delay). This entails a lower radiation dose, no chemotherapy and a shorter treatment period. This may lower their chances for complete tumor response and, as such, organ-sparing approaches. The purpose of this study was to compare the pathological complete response (pCR) rates between neoadjuvant CRT and SCRT-delay in patients with LARC in a nationwide database from the Netherlands. METHODS: In the population based Netherlands Cancer Registry, clinical stage III rectal cancer patients, diagnosed between 2008 and 2014, who underwent CRT or SCTR-delay were selected. pCR (ypT0N0), near pCR (ypT0-1N0), and tumor and nodal downstaging were compared between the treatment groups using multivariable logistic regression analysis. RESULTS: 386 patients underwent SCRT-delay and 3659 patients underwent CRT. The pCR-rate in the SCRT-delay group was significantly lower compared to the CRT-group (6.4% vs. 16.2%, p < 0.001). After adjustment for clinical tumor stage, clinical nodal stage and time interval to surgery, SCRT-delay patients were significantly less likely to reach pCR (adjusted odds ratio 0.3, 95%CI 0.2-0.5). Also, near-pCR (ypT0-1N0) as well as tumor and nodal downstaging was observed less often in the SCRT-delay group. CONCLUSION: Compared to patients treated with neoadjuvant CRT, those receiving SCRT and delayed surgery are less likely to develop pCR. Novel neoadjuvant treatment strategies for patients not fit enough for CRT are needed to increase their eligibility for organ-sparing treatments.

Utility Scores and Preferences for Surgical and Organ-Sparing Approaches for Treatment of Intermediate and High-Risk Rectal Cancer.

BACKGROUND: Organ-sparing approaches, including wait-and-see and local excision, are increasingly being offered to patients with rectal cancer following a good response to neoadjuvant therapy. Preferences regarding these treatment strategies are yet unknown. OBJECTIVE: This study aimed to determine the preferences and utility scores for rectal cancer treatment approaches. DESIGN: This is a cross-sectional study. SETTING: This study was conducted at the Radiation-Oncology Department of the University Medical Center Utrecht. PATIENTS: Fifty-seven patients with a history of rectal cancer and 38 volunteers were included. MAIN OUTCOME MEASURES: Participants assessed 6 hypothetical treatment-outcome scenarios, including short-course radiotherapy or chemoradiation followed by abdominoperineal resection, low anterior resection, local excision, or a wait-and-see approach. The hierarchy in preferences between scenarios was assessed by using ranking. Utilities were estimated with a visual analog scale and time trade-off. RESULTS: Organ-sparing approaches were ranked as the first preferred treatment option by 51% of the participants. Among all scenarios, wait-and-see was most often ranked highest by patients and volunteers (36% and 50%). Meanwhile, a substantial proportion ranked wait-and-see as their lowest preference (38% in patients and 35% in volunteers). Utility scores differed significantly between scenarios. Wait-and-see received a significantly higher score on the visual analog scale than the scenarios including abdominoperineal resection and the scenario including chemoradiation with low anterior resection, and a score similar to the scenarios including local excision and short-course radiotherapy with low anterior resection. LIMITATIONS: The study population consisted of patients with a history of rectal cancer treatment and volunteers related to patients. This may have influenced preferences. CONCLUSIONS: This study suggests that there is a wide disparity in preferences concerning organ-sparing approaches for rectal cancer in both patients with a history of rectal cancer and volunteers. Wait-and-see is often the highest preferred treatment, but it is also among the least preferred treatment options. These findings give insights into how patients may value the current rectal cancer treatment options. See Video Abstract at http://links.lww.com/DCR/A521.

The impact of postoperative complications on health-related quality of life in older patients with rectal cancer; a prospective cohort study.

OBJECTIVES: As result of the aging population and increasing rectal cancer incidence, more older patients undergo treatment for rectal cancer. This study compares treatment course, postoperative complications, and quality of life (QOL) between older and younger patients with rectal cancer and evaluates the impact of postoperative complications on QOL in the elderly. MATERIALS AND METHODS: Patients with rectal cancer participating in a prospective colorectal cancer cohort and referred for radiotherapy between 2013 and 2016 were included. QOL was assessed with the cancer questionnaire of the European Organisation for Research and Treatment of Cancer (EORTC QLQ-C30) before treatment and at three, six, and twelve months. Outcomes were compared between older patients (≥70years) and younger patients (<70years) and stratified by presence of postoperative complications. RESULTS: In total, 115 (33%) older patients and 230 (67%) younger patients were included. Compared to younger patients, older patients underwent significantly more often short-course radiation with delayed surgery (6.1% and 19.1% respectively) and less often chemoradiation (62.6% and 39.1% respectively), and were more likely to undergo a Hartmann procedure with permanent stoma (3.5% and 13.0% respectively) instead of sphincter-sparing surgery (43.9% and 29.6% respectively). Postoperative complication rates were similar (38.5% in older patients versus 34.7% in younger patients). Older patients had worse physical functioning at six and twelve months after diagnosis compared to younger patients. Presence of postoperative complications had a significant stronger impact on physical- and role functioning in older patients. CONCLUSION: Older patients undergo more often a tailored treatment approach for rectal cancer than younger patients. With this tailored approach, similar postoperative complication rates and QOL are achieved. However, postoperative complications have a larger negative impact on physical- and role functioning in older patients which indicates a need for better prediction of postoperative complications in the elderly.

The impact of retractor SPONGE-assisted laparoscopic surgery on duration of hospital stay and postoperative complications in patients with colorectal cancer (SPONGE trial): study protocol for a randomized controlled trial.

BACKGROUND: To achieve an adequate visual working field during laparoscopic colorectal surgery without disturbance of the small intestine, patients are positioned in the Trendelenburg position. This position results in hemodynamic changes that may increase the risk of cardiopulmonary complications and prolonged hospital stay. Recently, an intraoperative retractor sponge was introduced as an alternative to the Trendelenburg position during laparoscopic surgery. The objective of this trial is to study the impact of the use of an intraoperative retractor sponge on the duration of the hospital stay and risk of perioperative complications in patients undergoing laparoscopic surgery for colorectal cancer. METHODS/DESIGN: The SPONGE trial is a monocenter study and follows the cohort multiple randomized controlled trial (cmRCT) design. It will be conducted within a multicenter prospective observational cohort of colorectal cancer patients of all stages, for whom longitudinal clinical data and patient-reported outcomes are collected. Patients within the cohort, who will undergo laparoscopic surgery for distal colon or rectal cancer, are eligible for inclusion and form a subcohort. From this subcohort, a 1:1 random sample will be offered to undergo surgery with the use of the retractor sponge. Patients from the subcohort who are not selected will undergo standard treatment, that is, surgery in the Trendelenburg position. The primary endpoint is the duration of the postoperative hospital stay. Secondary outcomes are duration of surgery; intraoperative blood loss and fluid balance; and postoperative body temperature, oxygenation and complications. Both arms require 94 patients. DISCUSSION: This study is the first randomized controlled trial to evaluate the effect of sponge-assisted laparoscopic colorectal surgery in comparison with standard Trendelenburg position on hospital stay and peri- and postoperative complications. Results of this study will also be relevant for other surgical procedures in the pelvic region. The present study is the second randomized controlled trial according to the cmRCT design, which is embedded within our colorectal cancer cohort. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02574013 . Registered 27 September 2015.