Work Ability in Patients With Stage I to IV Colon Cancer: Results of the Dutch Prospective Colorectal Cancer Cohort.

BACKGROUND: Colon cancer affects a patient's ability to work. Many patients who have colon cancer are employed at the time of diagnosis. OBJECTIVE: We evaluated work ability during the first 2 years after colon cancer diagnosis. DESIGN: This study is a national prospective study, the Prospective Dutch ColoRectal Cancer cohort, including clinical data and patient-reported outcomes. SETTINGS: Data were collected in 59 medical centers in the Netherlands. PATIENTS: Patients <67 years of age with stage I to IV colon cancer and who completed Work Ability Index questionnaires were selected. MAIN OUTCOME MEASURES: Work ability was assessed at baseline, 3, 6, 12, 18, and 24 months. The Work Ability Index (range, 0 to 49) was evaluated using linear mixed models. Outcomes were matched to population controls without cancer. RESULTS: Of 390 patients, 84% had paid employment. Work ability of patients with stage I to IV colon cancer was significantly lower at the time of diagnosis than in matched population controls (31 ± 8.2 and 41 ± 5.6). Patients with stage I to III disease receiving surgery only regained Work Ability Index scores comparable to matched population controls at 18 months. Patients receiving adjuvant systemic treatment initially demonstrated a decrease in work ability with improvements from 6 months onward and normalization at 24 months. Patients with stage IV disease did not demonstrate improvements in work ability outcomes over time. Work ability scores were negatively influenced by the administration of systemic treatment and ≥1 comorbidities. LIMITATIONS: Only patients with patient-reported outcomes and work at baseline were included in this analysis. Also, questionnaire response rates decreased over time. CONCLUSIONS: Work ability in patients with colon cancer is decreased for a prolonged time. Recovery depends on disease stage, type of treatment, and comorbidities. Patients with stage I to III disease treated with curative surgery alone were the first to regain work ability, followed by patients who receive adjuvant chemotherapy. Patients with stage IV disease did not regain work ability. See Video Abstract at http://links.lww.com/DCR/B759 . CAPACIDAD LABORAL EN PACIENTES CON CNCER DE COLON EN ESTADIO IIV RESULTADOS PROSPECTIVOS DE CNCER COLORECTAL EN UNA COHORTE HOLANDESA: ANTECEDENTES:El cáncer de colon afecta la capacidad de trabajo en un paciente. Muchos pacientes con cáncer de colon están empleados en el momento del diagnóstico.OBJETIVO:Evaluamos la capacidad laboral durante los dos primeros años posteriores al diagnóstico de cáncer de colon.DISEÑO:Es un estudio prospectivo nacional, la cohorte de cáncer colorrectal holandés, incluye datos clínicos y resultados informados por los pacientes.ENTORNO CLINICO:Se recopilaron datos de 59 centros médicos en los Países Bajos.PACIENTES:Se seleccionaron pacientes < 67 años, con cáncer de colon en estadio I-IV, que completaron los cuestionarios de índice de capacidad para el trabajo.PRINCIPALES MEDIDAS DE VALORACIÓN:La capacidad para el trabajo se evaluó al inicio, a los 3, 6, 12, 18 y 24 meses. El índice de capacidad para el trabajo (que va de 0 a 49) se evaluó mediante modelos lineales mixtos. Los resultados fueron comparados con el grupo control sin cáncer.RESULTADOS:De 390 pacientes, el 84% tenía un empleo remunerado. La capacidad de trabajo de los pacientes en estadio I-IV fue significativamente menor en el momento del diagnóstico en comparación con el grupo control (31 ± 8,2 y 41 ± 5,6, respectivamente). Los pacientes con enfermedad en estadio I-III que recibieron cirugía lograron recuperar puntajes del índice de capacidad laboral comparables a los controles a los 18 meses. Los pacientes que recibieron tratamiento sistémico adyuvante inicialmente demostraron una disminución en la capacidad de trabajo con mejoras a partir de los 6 meses en adelante y una normalización a los 24 meses. Los pacientes en estadio IV no demostraron mejoras en los resultados de la capacidad laboral a lo largo del tiempo. Las puntuaciones de capacidad para el trabajo se vieron influidas negativamente por la administración del tratamiento sistémico y la existencia de ≥1 comorbilidades.LIMITACIONES:En este análisis solo se incluyeron los pacientes con resultados y trabajo desde el inicio del estudio. Además, las tasas de respuesta al cuestionario disminuyeron con el tiempo.CONCLUSIONES:La capacidad de trabajo en pacientes con cáncer de colon se reduce durante un tiempo prolongado. La recuperación depende del estadio de la enfermedad, el tipo de tratamiento y la comorbilidad. Los pacientes con enfermedad en estadio I-III tratados con cirugía curativa exclusivamente, son los primeros en recuperar la capacidad para trabajar, seguidos de los pacientes que reciben quimioterapia adyuvante. Los pacientes con enfermedad en estadio IV no recuperan la capacidad para trabajar. Consulte Video Resumen en http://links.lww.com/DCR/B759 . (Traducción- Dr. Ingrid Melo )

Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colon cancer at high risk of peritoneal carcinomatosis; the COLOPEC randomized multicentre trial

Contains fulltext : 153610.pdf (publisher's version ) (Open Access)BACKGROUND: The peritoneum is the second most common site of recurrence in colorectal cancer. Early detection of peritoneal carcinomatosis (PC) by imaging is difficult. Patients eventually presenting with clinically apparent PC have a poor prognosis. Median survival is only about five months if untreated and the benefit of palliative systemic chemotherapy is limited. Only a quarter of patients are eligible for curative treatment, consisting of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CR/HIPEC). However, the effectiveness depends highly on the extent of disease and the treatment is associated with a considerable complication rate. These clinical problems underline the need for effective adjuvant therapy in high-risk patients to minimize the risk of outgrowth of peritoneal micro metastases. Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) seems to be suitable for this purpose. Without the need for cytoreductive surgery, adjuvant HIPEC can be performed with a low complication rate and short hospital stay. METHODS/DESIGN: The aim of this study is to determine the effectiveness of adjuvant HIPEC in preventing the development of PC in patients with colon cancer at high risk of peritoneal recurrence. This study will be performed in the nine Dutch HIPEC centres, starting in April 2015. Eligible for inclusion are patients who underwent curative resection for T4 or intra-abdominally perforated cM0 stage colon cancer. After resection of the primary tumour, 176 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously or shortly after the primary resection. Oxaliplatin will be used as chemotherapeutic agent, for 30 min at 42-43 degrees C. Just before HIPEC, 5-fluorouracil and leucovorin will be administered intravenously. Primary endpoint is peritoneal disease-free survival at 18 months. Diagnostic laparoscopy will be performed routinely after 18 months postoperatively in both arms of the study in patients without evidence of disease based on routine follow-up using CT imaging and CEA. DISCUSSION: Adjuvant HIPEC is assumed to reduce the expected 25 % absolute risk of PC in patients with T4 or perforated colon cancer to a risk of 10 %. This reduction is likely to translate into a prolonged overall survival. TRIAL REGISTRATION NUMBER: NCT02231086 (Clinicaltrials.gov)

Survival of patients with colorectal peritoneal metastases is affected by treatment disparities among hospitals of diagnosis: A nationwide population-based study

Contains fulltext : 174509.pdf (publisher's version ) (Closed access)BACKGROUND: In the Netherlands, surgery for peritoneal metastases of colorectal cancer (PMCRC) is centralised, whereas PMCRC is diagnosed in all hospitals. This study assessed whether hospital of diagnosis affects treatment selection and overall survival (OS). METHODS: Between 2005 and 2015, all patients with synchronous PMCRC without systemic metastases were selected from the Netherlands Cancer Registry. Treatment was classified as cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), systemic therapy or other/no treatment. Hospitals of diagnosis were classified as: (1) non-teaching or academic/teaching hospital and (2) HIPEC centre or referring hospital. Referring hospitals were further classified based on the frequency of CRS/HIPEC as high-, medium- or low-frequency hospital. Multivariable regression analyses were used to assess the independent influence of hospital categories on the likelihood of CRS/HIPEC and OS. RESULTS: A total of 2661 patients, diagnosed in 89 hospitals, were included. At individual hospital level, CRS/HIPEC and systemic therapy ranged from 0% to 50% and 6% to 67%, respectively. Hospital of diagnosis influenced the likelihood of CRS/HIPEC: 33% versus 13% for HIPEC centres versus referring hospitals (odds ratio (OR) 3.66 [2.40-5.58]) and 11% versus 17% for non-teaching hospitals versus academic/teaching hospitals (OR 0.60 [0.47-0.77]). Hospital of diagnosis affected median OS: 14.1 versus 9.6 months for HIPEC centres versus referring hospitals (hazard ratio (HR) 0.82 [0.67-0.99]) and 8.7 versus 11.5 months for non-teaching hospitals versus academic/teaching hospitals (HR 1.15 [1.06-1.26]). Compared with diagnosis in medium-frequency referring hospitals, median OS was increased in high-frequency referring hospitals (12.6 months, HR 0.82 [0.73-0.91]) and reduced in low-frequency referring hospitals (8.1 months, HR 1.12 [1.01-1.24]). CONCLUSION: Treatment disparities among hospitals of diagnosis and their impact on survival indicate suboptimal treatment selection for PMCRC

A multi-centred randomised trial of radical surgery versus adjuvant chemoradiotherapy after local excision for early rectal cancer

Contains fulltext : 172310.pdf (publisher's version ) (Open Access)BACKGROUND: Rectal cancer surgery is accompanied with high morbidity and poor long term functional outcome. Screening programs have shown a shift towards more early staged cancers. Patients with early rectal cancer can potentially benefit significantly from rectal preserving therapy. For the earliest stage cancers, local excision is sufficient when the risk of lymph node disease and subsequent recurrence is below 5 %. However, the majority of early cancers are associated with an intermediate risk of lymph node involvement (5-20 %) suggesting that local excision alone is not sufficient, while completion radical surgery, which is currently standard of care, could be a substantial overtreatment for this group of patients. METHODS/STUDY DESIGN: In this multicentre randomised trial, patients with an intermediate risk T1-2 rectal cancer, that has been locally excised using an endoluminal technique, will be randomized between adjuvant chemo-radiotherapylimited to the mesorectum and standard completion total mesorectal excision (TME). To strictly monitor the risk of locoregional recurrence in the experimental arm and enable early salvage surgery, there will be additional follow up with frequent MRI and endoscopy. The primary outcome of the study is three-year local recurrence rate. Secondary outcomes are morbidity, disease free and overall survival, stoma rate, functional outcomes, health related quality of life and costs. The design is a non inferiority study with a total sample size of 302 patients. DISCUSSION: The results of the TESAR trial will potentially demonstrate that adjuvant chemoradiotherapy is an oncological safe treatment option in patients who are confronted with the difficult clinical dilemma of a radically removed intermediate risk early rectal cancer by polypectomy or transanal surgery that is conventionally treated with subsequent radical surgery. Preserving the rectum using adjuvant radiotherapy is expected to significantly improve morbidity, function and quality of life if compared to completion TME surgery. TRIAL REGISTRATION: NCT02371304 , registration date: February 2015

Laparoscopic peritoneal lavage or sigmoidectomy for perforated diverticulitis with purulent peritonitis: a multicentre, parallel-group, randomised, open-label trial

Item does not contain fulltextBACKGROUND: Case series suggest that laparoscopic peritoneal lavage might be a promising alternative to sigmoidectomy in patients with perforated diverticulitis. We aimed to assess the superiority of laparoscopic lavage compared with sigmoidectomy in patients with purulent perforated diverticulitis, with respect to overall long-term morbidity and mortality. METHODS: We did a multicentre, parallel-group, randomised, open-label trial in 34 teaching hospitals and eight academic hospitals in Belgium, Italy, and the Netherlands (the Ladies trial). The Ladies trial is split into two groups: the LOLA group comparing laparoscopic lavage with sigmoidectomy and the DIVA group comparing Hartmann's procedure with sigmoidectomy plus primary anastomosis. The DIVA section of this trial is still underway but here we report the results of the LOLA section. Patients with purulent perforated diverticulitis were enrolled for LOLA, excluding patients with faecal peritonitis, aged older than 85 years, with high-dose steroid use (>/=20 mg daily), and haemodynamic instability. Patients were randomly assigned (2:1:1; stratified by age [/=60 years]) using secure online computer randomisation to laparoscopic lavage, Hartmann's procedure, or primary anastomosis in a parallel design after diagnostic laparoscopy. Patients were analysed according to a modified intention-to-treat principle and were followed up after the index operation at least once in the outpatient setting and after sigmoidoscopy and stoma reversal, according to local protocols. The primary endpoint was a composite endpoint of major morbidity and mortality within 12 months. This trial is registered with ClinicalTrials.gov, number NCT01317485. FINDINGS: Between July 1, 2010, and Feb 22, 2013, 90 patients were randomly assigned in the LOLA section of the Ladies trial when the study was terminated by the data and safety monitoring board because of an increased event rate in the lavage group. Two patients were excluded for protocol violations. The primary endpoint occurred in 30 (67%) of 45 patients in the lavage group and 25 (60%) of 42 patients in the sigmoidectomy group (odds ratio 1.28, 95% CI 0.54-3.03, p=0.58). By 12 months, four patients had died after lavage and six patients had died after sigmoidectomy (p=0.43). INTERPRETATION: Laparoscopic lavage is not superior to sigmoidectomy for the treatment of purulent perforated diverticulitis. FUNDING: Netherlands Organisation for Health Research and Development

Perioperative Systemic Therapy Versus Cytoreductive Surgery and HIPEC Alone for Resectable Colorectal Peritoneal Metastases: Patient-Reported Outcomes of a Randomized Phase II Trial.

BACKGROUND: As part of a randomized phase II trial in patients with isolated resectable colorectal peritoneal metastases (CPMs), the present study compared patient-reported outcomes (PROs) of patients treated with perioperative systemic therapy versus cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) alone. Also, PROs of patients receiving perioperative systemic therapy were explored. PATIENTS AND METHODS: Eligible patients were randomized to perioperative systemic therapy (experimental) or CRS-HIPEC alone (control). PROs were assessed using EORTC QLQ-C30, QLQ-CR29, and EQ-5D-5L questionnaires at baseline, after neoadjuvant treatment (experimental), and at 3 and 6 months postoperatively. Linear mixed modeling was used to compare five predefined PROs (visual analog scale, global health status, physical functioning, fatigue, C30 summary score) between arms and to longitudinally analyze PROs in the experimental arm. RESULTS: Of 79 analyzed patients, 37 (47%) received perioperative systemic therapy. All predefined PROs were comparable between arms at all timepoints and returned to baseline at 3 or 6 months postoperatively. The experimental arm had worsening of fatigue [mean difference (MD) + 14, p = 0.001], loss of appetite (MD + 15, p = 0.003), hair loss (MD + 18, p < 0.001), and loss of taste (MD + 27, p < 0.001) after neoadjuvant treatment. Except for loss of appetite, these PROs returned to baseline at 3 or 6 months postoperatively. CONCLUSIONS: In patients with resectable CPM randomized to perioperative systemic therapy or CRS-HIPEC alone, PROs were comparable between arms and returned to baseline postoperatively. Together with the trial's previously reported feasibility and safety data, these findings show acceptable tolerability of perioperative systemic therapy in this setting

Effects of hormone replacement therapy on cardiovascular function in postmenopausal women, a brief review

BACKGROUND: Early enteral feeding through a nasoenteric feeding tube is often used in patients with severe acute pancreatitis to prevent gut-derived infections, but evidence to support this strategy is limited. We conducted a multicenter, randomized trial comparing early nasoenteric tube feeding with an oral diet at 72 hours after presentation to the emergency department in patients with acute pancreatitis. METHODS: We enrolled patients with acute pancreatitis who were at high risk for complications on the basis of an Acute Physiology and Chronic Health Evaluation II score of 8 or higher (on a scale of 0 to 71, with higher scores indicating more severe disease), an Imrie or modified Glasgow score of 3 or higher (on a scale of 0 to 8, with higher scores indicating more severe disease), or a serum C-reactive protein level of more than 150 mg per liter. Patients were randomly assigned to nasoenteric tube feeding within 24 hours after randomization (early group) or to an oral diet initiated 72 hours after presentation (on-demand group), with tube feeding provided if the oral diet was not tolerated. The primary end point was a composite of major infection (infected pancreatic necrosis, bacteremia, or pneumonia) or death during 6 months of follow-up. RESULTS: A total of 208 patients were enrolled at 19 Dutch hospitals. The primary end point occurred in 30 of 101 patients (30%) in the early group and in 28 of 104 (27%) in the on-demand group (risk ratio, 1.07; 95% confidence interval, 0.79 to 1.44; P=0.76). There were no significant differences between the early group and the on-demand group in the rate of major infection (25% and 26%, respectively; P=0.87) or death (11% and 7%, respectively; P=0.33). In the on-demand group, 72 patients (69%) tolerated an oral diet and did not require tube feeding. CONCLUSIONS: This trial did not show the superiority of early nasoenteric tube feeding, as compared with an oral diet after 72 hours, in reducing the rate of infection or death in patients with acute pancreatitis at high risk for complications. (Funded by the Netherlands Organization for Health Research and Development and others; PYTHON Current Controlled Trials number, ISRCTN18170985.)

Endoscopic or surgical step-up approach for infected necrotising pancreatitis: a multicentre randomised trial

Contains fulltext : 181861.pdf (publisher's version ) (Closed access)BACKGROUND: Infected necrotising pancreatitis is a potentially lethal disease and an indication for invasive intervention. The surgical step-up approach is the standard treatment. A promising alternative is the endoscopic step-up approach. We compared both approaches to see whether the endoscopic step-up approach was superior to the surgical step-up approach in terms of clinical and economic outcomes. METHODS: In this multicentre, randomised, superiority trial, we recruited adult patients with infected necrotising pancreatitis and an indication for invasive intervention from 19 hospitals in the Netherlands. Patients were randomly assigned to either the endoscopic or the surgical step-up approach. The endoscopic approach consisted of endoscopic ultrasound-guided transluminal drainage followed, if necessary, by endoscopic necrosectomy. The surgical approach consisted of percutaneous catheter drainage followed, if necessary, by video-assisted retroperitoneal debridement. The primary endpoint was a composite of major complications or death during 6-month follow-up. Analyses were by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN09186711. FINDINGS: Between Sept 20, 2011, and Jan 29, 2015, we screened 418 patients with pancreatic or extrapancreatic necrosis, of which 98 patients were enrolled and randomly assigned to the endoscopic step-up approach (n=51) or the surgical step-up approach (n=47). The primary endpoint occurred in 22 (43%) of 51 patients in the endoscopy group and in 21 (45%) of 47 patients in the surgery group (risk ratio [RR] 0.97, 95% CI 0.62-1.51; p=0.88). Mortality did not differ between groups (nine [18%] patients in the endoscopy group vs six [13%] patients in the surgery group; RR 1.38, 95% CI 0.53-3.59, p=0.50), nor did any of the major complications included in the primary endpoint. INTERPRETATION: In patients with infected necrotising pancreatitis, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing major complications or death. The rate of pancreatic fistulas and length of hospital stay were lower in the endoscopy group. The outcome of this trial will probably result in a shift to the endoscopic step-up approach as treatment preference. FUNDING: The Dutch Digestive Disease Foundation, Fonds NutsOhra, and the Netherlands Organization for Health Research and Development

Perioperative Systemic Therapy vs Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Alone for Resectable Colorectal Peritoneal Metastases: A Phase 2 Randomized Clinical Trial

IMPORTANCE: To date, no randomized clinical trials have investigated perioperative systemic therapy relative to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) alone for resectable colorectal peritoneal metastases (CPM). OBJECTIVE: To assess the feasibility and safety of perioperative systemic therapy in patients with resectable CPM and the response of CPM to neoadjuvant treatment. DESIGN, SETTING, AND PARTICIPANTS: An open-label, parallel-group phase 2 randomized clinical trial in all 9 Dutch tertiary centers for the surgical treatment of CPM enrolled participants between June 15, 2017, and January 9, 2019. Participants were patients with pathologically proven isolated resectable CPM who did not receive systemic therapy within 6 months before enrollment. INTERVENTIONS: Randomization to perioperative systemic therapy or CRS-HIPEC alone. Perioperative systemic therapy comprised either four 3-week neoadjuvant and adjuvant cycles of CAPOX (capecitabine and oxaliplatin), six 2-week neoadjuvant and adjuvant cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin), or six 2-week neoadjuvant cycles of FOLFIRI (fluorouracil, leucovorin, and irinotecan) and either four 3-week adjuvant cycles of capecitabine or six 2-week adjuvant cycles of fluorouracil with leucovorin. Bevacizumab was added to the first 3 (CAPOX) or 4 (FOLFOX/FOLFIRI) neoadjuvant cycles. MAIN OUTCOMES AND MEASURES: Proportions of macroscopic complete CRS-HIPEC and Clavien-Dindo grade 3 or higher postoperative morbidity. Key secondary outcomes were centrally assessed rates of objective radiologic and major pathologic response of CPM to neoadjuvant treatment. Analyses were done modified intention-to-treat in patients starting neoadjuvant treatment (experimental arm) or undergoing upfront surgery (control arm). RESULTS: In 79 patients included in the analysis (43 [54%] men; mean [SD] age, 62 [10] years), experimental (n = 37) and control (n = 42) arms did not differ significantly regarding the proportions of macroscopic complete CRS-HIPEC (33 of 37 [89%] vs 36 of 42 [86%] patients; risk ratio, 1.04; 95% CI, 0.88-1.23; P = .74) and Clavien-Dindo grade 3 or higher postoperative morbidity (8 of 37 [22%] vs 14 of 42 [33%] patients; risk ratio, 0.65; 95% CI, 0.31-1.37; P = .25). No treatment-related deaths occurred. Objective radiologic and major pathologic response rates of CPM to neoadjuvant treatment were 28% (9 of 32 evaluable patients) and 38% (13 of 34 evaluable patients), respectively. CONCLUSIONS AND RELEVANCE: In this randomized phase 2 trial in patients diagnosed with resectable CPM, perioperative systemic therapy seemed feasible, safe, and able to induce response of CPM, justifying a phase 3 trial. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02758951

Perioperative systemic therapy and cytoreductive surgery with HIPEC versus upfront cytoreductive surgery with HIPEC alone for isolated resectable colorectal peritoneal metastases: protocol of a multicentre, open-label, parallel-group, phase II-III, randomised, superiority study (CAIRO6)

Contains fulltext : 207201.pdf (publisher's version ) (Open Access)BACKGROUND: Upfront cytoreductive surgery with HIPEC (CRS-HIPEC) is the standard treatment for isolated resectable colorectal peritoneal metastases (PM) in the Netherlands. This study investigates whether addition of perioperative systemic therapy to CRS-HIPEC improves oncological outcomes. METHODS: This open-label, parallel-group, phase II-III, randomised, superiority study is performed in nine Dutch tertiary referral centres. Eligible patients are adults who have a good performance status, histologically or cytologically proven resectable PM of a colorectal adenocarcinoma, no systemic colorectal metastases, no systemic therapy for colorectal cancer within six months prior to enrolment, and no previous CRS-HIPEC. Eligible patients are randomised (1:1) to perioperative systemic therapy and CRS-HIPEC (experimental arm) or upfront CRS-HIPEC alone (control arm) by using central randomisation software with minimisation stratified by a peritoneal cancer index of 0-10 or 11-20, metachronous or synchronous PM, previous systemic therapy for colorectal cancer, and HIPEC with oxaliplatin or mitomycin C. At the treating physician's discretion, perioperative systemic therapy consists of either four 3-weekly neoadjuvant and adjuvant cycles of capecitabine with oxaliplatin (CAPOX), six 2-weekly neoadjuvant and adjuvant cycles of 5-fluorouracil/leucovorin with oxaliplatin (FOLFOX), or six 2-weekly neoadjuvant cycles of 5-fluorouracil/leucovorin with irinotecan (FOLFIRI) followed by four 3-weekly (capecitabine) or six 2-weekly (5-fluorouracil/leucovorin) adjuvant cycles of fluoropyrimidine monotherapy. Bevacizumab is added to the first three (CAPOX) or four (FOLFOX/FOLFIRI) neoadjuvant cycles. The first 80 patients are enrolled in a phase II study to explore the feasibility of accrual and the feasibility, safety, and tolerance of perioperative systemic therapy. If predefined criteria of feasibility and safety are met, the study continues as a phase III study with 3-year overall survival as primary endpoint. A total of 358 patients is needed to detect the hypothesised 15% increase in 3-year overall survival (control arm 50%; experimental arm 65%). Secondary endpoints are surgical characteristics, major postoperative morbidity, progression-free survival, disease-free survival, health-related quality of life, costs, major systemic therapy related toxicity, and objective radiological and histopathological response rates. DISCUSSION: This is the first randomised study that prospectively compares oncological outcomes of perioperative systemic therapy and CRS-HIPEC with upfront CRS-HIPEC alone for isolated resectable colorectal PM. TRIAL REGISTRATION: Clinicaltrials.gov/ NCT02758951 , NTR/ NTR6301 , ISRCTN/ ISRCTN15977568 , EudraCT/ 2016-001865-99