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The TME trial investigated the value of preoperative short-term radiotherapy in combination with total mesorectal excision (TME). Long-term results are reported after a median follow-up of 12 years. Between Jan 12, 1996, and Dec 31, 1999, 1861 patients with resectable rectal cancer without evidence of distant disease were randomly assigned to TME preceded by 5 × 5 Gy radiotherapy or TME alone (ratio 1:1). Randomisation was based on permuted blocks of six with stratification according to centre and expected type of surgery. The primary endpoint was local recurrence, analysed for all eligible patients who underwent a macroscopically complete local resection. 10-year cumulative incidence of local recurrence was 5% in the group assigned to radiotherapy and surgery and 11% in the surgery-alone group (p<0·0001). The effect of radiotherapy became stronger as the distance from the anal verge increased. However, when patients with a positive circumferential resection margin were excluded, the relation between distance from the anal verge and the effect of radiotherapy disappeared. Patients assigned to radiotherapy had a lower overall recurrence and when operated with a negative circumferential resection margin, cancer-specific survival was higher. Overall survival did not differ between groups. For patients with TNM stage III cancer with a negative circumferential resection margin, 10-year survival was 50% in the preoperative radiotherapy group versus 40% in the surgery-alone group (p=0·032). For all eligible patients, preoperative short-term radiotherapy reduced 10-year local recurrence by more than 50% relative to surgery alone without an overall survival benefit. For patients with a negative resection margin, the effect of radiotherapy was irrespective of the distance from the anal verge and led to an improved cancer-specific survival, which was nullified by an increase in other causes of death, resulting in an equal overall survival. Nevertheless, preoperative short-term radiotherapy significantly improved 10-year survival in patients with a negative circumferential margin and TNM stage III. Future staging techniques should offer possibilities to select patient groups for which the balance between benefits and side-effects will result in sufficiently large gains. The Dutch Cancer Society, the Dutch National Health Council, and the Swedish Cancer Society.

IntroductionPretreatment enlarged lateral lymph nodes (LLN) in patients with locally advanced low rectal cancer are predictive for local recurrences after neoadjuvant (chemo)radiotherapy (n(C)RT) followed by total mesorectal excision (TME). Not much is known of the impact on oncological outcomes when in addition malignant features are present in enlarged LLN.Patients and MethodsA multicenter retrospective cohort study was conducted at five tertiary referral centers in the Netherlands and Australia. All patients were diagnosed with locally advanced low rectal cancer with LLN on pretreatment magnetic resonance imaging (MRI) and underwent n(C)RT followed by TME. LLN were considered enlarged with a short axis of ≥ 5 mm. Malignant features were defined as nodes with internal heterogeneity and/or border irregularity. Outcomes of interest were local recurrence-free survival (LRFS), distant metastatic-free survival (DMFS), and overall survival (OS).ResultsOut of 115 patients, the majority was male (75%) and the median age was 64 years (range 26–85 years). Median pretreatment LLN short axis was 7 mm (range 5–28 mm), and 60 patients (52%) had malignant features. After a median follow-up of 47 months, patients with larger LLN (7 + mm) had a worse LRFS (p = 0.01) but no difference in DMFS (p = 0.37) and OS (p = 0.54) compared with patients with smaller LLN (5–6 mm). LLN patients with malignant features had no difference in LRFS (p = 0.20) but worse DMFS (p = 0.004) and OS (p = 0.006) compared with patients without malignant features in the LLN. Cox regression analysis identified LLN short axis as an independent factor for LR. Malignant features in LLN were an independent factor for DMFS.ConclusionThe current study suggests that pretreatment enlarged LLN that also harbor malignant features are predictive of a worse DMFS. More studies will be required to further explore the role of malignant features in LLN.

•One fifth of operated colorectal cancer patients will develop metachronous metastases.•Colon and rectal cancer patients have different patterns of metastatic spread.•Median time to diagnosis depends on site of metastasis.•The risk for metastases is associated with patient and tumour characteristics. This study aimed to provide information on timing, anatomical location, and predictors for metachronous metastases of colorectal cancer based on a large consecutive series of non-selected patients. All patients operated on with curative intent for colorectal cancer (TanyNanyM0) between 2003 and 2008 in the Dutch Eindhoven Cancer Registry were included (N=5671). By means of active follow-up by the Cancer Registry staff within ten hospitals, data on development of metastatic disease were collected. Median follow-up was 5.0 years. Of the 5671 colorectal cancer patients, 1042 (18%) were diagnosed with metachronous metastases. Most common affected sites were the liver (60%), lungs (39%), extra-regional lymph nodes (22%), and peritoneum (19%). 86% of all metastases was diagnosed within three years and the median time to diagnosis was 17 months (interquartile range 10–29 months). Male gender (HR=1.2, 95%CI 1.03–1.32), an advanced primary T-stage (T4 vs. T3 HR=1.6, 95%CI 1.32–1.90) and N-stage (N1 vs. N0 HR=2.8, 95%CI 2.42–3.30 and N2 vs. N0 HR=4.5, 95%CI 3.72–5.42), high-grade tumour differentiation (HR=1.4, 95%CI 1.17–1.62), and a positive (HR=2.1, 95%CI 1.68–2.71) and unknown (HR=1.7, 95%CI 1.34–2.22) resection margin were predictors for metachronous metastases. Different patterns of metastatic spread were observed for colon and rectal cancer patients and differences in time to diagnosis were found. Knowledge on these patterns and predictors for metachronous metastases may enhance tailor-made follow-up schemes leading to earlier detection of metastasized disease and increased curative treatment options.

The cornerstone of treatment for rectal cancer is resectional treatment according to the principles of total mesorectal excision (TME). However, population-based registries show that improvements in outcome after resectional treatment occur mainly in younger patients. Furthermore, 6-month postoperative mortality is significantly increased in elderly patients (≥75 years of age) compared with younger patients (<75 years of age). Several confounding factors, such as treatment-related complications and comorbidity, are thought to be responsible for these disappointing findings. Thus, major resectional treatment is not advantageous for all older patients with rectal cancer. However, the Dutch TME trial showed a good response to a short course of neoadjuvant radiotherapy in elderly patients. Biological responses to cancer treatment seem to change with age, and, therefore, individualised cancer treatments should be used that take into account the heterogeneity of ageing. For elderly patients who retain a good physical and mental condition, treatment that is given to younger patients is deemed appropriate, whereas for those with diminished physiological reserves and comorbid conditions, alternative treatments that keep surgical trauma to a minimum and optimise the use of radiotherapy might be more suitable.

Background Studies on the impact of comorbidity and age on postoperative outcome after gastrointestinal tumor resection are scarce. In this study we investigated the impact of comorbidity and age on 30-, 60-, and 90-day mortality after resection of esophageal, gastric, periampullary, colon, and rectal cancer. Methods The study included 8,583 patients recorded in the population-based Netherlands Cancer Registry, regions Eindhoven (Eindhoven Cancer Registry) and Mid and South Limburg, who underwent resection for cancer stage I–III. Patients were diagnosed between 2005 and 2010. Age was categorized as <65, 65–74, and ≥75 years. Results Comorbidity was present in more than two-thirds ( n  = 5,910) of patients. The 30-day mortality rates ranged from 0.5 % for rectal cancer patients <65 years to 12.8 % for gastric cancer patients ≥75 years. Patients with comorbidity who underwent esophageal tumor resection had the highest mortality rates, ranging from 8.4 % for 30-day to 12.0 % for 90-day mortality, while rectal cancer patients had the lowest rates, that is, 4.3–6.4 %, respectively. In multivariable analyses, cardiac disease (odds ratio [OR] = 1.74, 95 % confidence interval [95 % CI] = 1.32–2.30), vascular disease (OR = 1.41, 95 % CI = 1.02–1.95) and previous malignancies (OR = 1.38, 95 % CI = 1.02–1.86) in colon cancer, and cardiac disease (OR = 1.81, 95 % CI = 1.10–2.98) and vascular disease (OR = 1.95, 95 % CI = 1.11–3.42) in rectal cancer were associated with the highest 30-day mortality. Conclusions Postoperative mortality extends beyond 30 days. Comorbidity and older age are associated with early postoperative mortality after gastrointestinal cancer resection. Underlying comorbidity should be identified preoperatively with attention to patients’ specific needs to optimally attenuate risk prior to surgery. A less aggressive treatment approach may well be considered in these groups.

In many patients with rectal cancer, defunctioning stomas are created to limit the consequences of anastomotic leakage. Although intended to be temporary, a substantial proportion of these stomas might never be reversed for various reasons. We aimed to describe stoma policy by use of data from the total mesorectal excision (TME) trial in patients with rectal cancer and to identify factors that limit stoma reversal. 924 Dutch patients with rectal cancer who underwent a low anterior resection were selected from the TME trial, a prospective, randomised multicentre trial studying the effects of short-term preoperative radiotherapy in 1861 patients who underwent TME. Creation of stomas and time to stoma reversal were analysed retrospectively by use of multivariate analysis. In 523 of 924 (57%) patients, a primary stoma (defined as a stoma created at the time of TME) was constructed after a low anterior resection. Geographical differences in the number of primary stomas constructed were reported throughout the Netherlands. 19% of stomas that were created were never reversed. Postoperative complications and secondary constructed stomas (defined as a stoma created during a second or subsequent procedure after TME) were associated with a high likelihood of a permanent stoma. However, perioperative complications were not a limiting factor for stoma closure. Postoperative complications are an important limiting factor for stoma reversal because, after occurrence of these complications, patients and surgeons might be reluctant to reverse the stoma, so a substantial proportion of these stomas are never closed. Future guidelines for stoma creation and closure should consider these factors.

Malignant lateral lymph nodes (LLNs) in low, locally advanced rectal cancer can cause (ipsi-lateral) local recurrences ((L)LR). Accurate identification is, therefore, essential. This study explored LLN features to create an artificial intelligence prediction model, estimating the risk of (L)LR. This retrospective multicentre cohort study examined 196 patients diagnosed with rectal cancer between 2008 and 2020 from three tertiary centres in the Netherlands. Primary and restaging T2W magnetic resonance imaging and clinical features were used. Visible LLNs were segmented and used for a multi-channel convolutional neural network. A deep learning model was developed and trained for the prediction of (L)LR according to malignant LLNs. Combined imaging and clinical features resulted in AUCs of 0.78 and 0.80 for LR and LLR, respectively. The sensitivity and specificity were 85.7% and 67.6%, respectively. Class activation map explainability methods were applied and consistently identified the same high-risk regions with structural similarity indices ranging from 0.772–0.930. This model resulted in good predictive value for (L)LR rates and can form the basis of future auto-segmentation programs to assist in the identification of high-risk patients and the development of risk stratification models.

Purpose Sexual dysfunction among patients with colorectal cancer is frequently reported. Studies examining patients’ sexual health care needs are rare. We examined the sexual health care needs after colorectal cancer treatment according to patients, partners, and health care professionals (HCPs). Factors that impede or facilitate the quality of this care were identified. Method Participants were recruited from three Dutch hospitals: St. Elisabeth, TweeSteden, and Catharina hospitals. Patients ( n  = 21), partners ( n  = 9), and 10 HCPs participated in eight focus groups. Results It is important to regularly evaluate and manage sexual issues. This does not always occur. Almost all participants reported a lack of knowledge and feelings of embarrassment or inappropriateness as barriers to discuss sexuality. HCPs reported stereotypical assumptions regarding the need for care based on age, sex, and partner status. The HCPs debated on whose responsibility it is that sexuality is discussed with patients. Factors within the organization, such as insufficient re-discussion of sexuality during (long-term) follow-up and unsatisfactory (knowledge of the) referral system impeded sexual health care. The HCPs could facilitate adequate sexual health care by providing patient-tailored information and permission to discuss sex, normalizing sexual issues, and establishing an adequate referral system. It is up to the patients and partners to demarcate the extent of sexual health care needed. Conclusions Our findings illustrate the need for patient-tailored sexual health care and the complexity of providing/receiving this care. An adequate referral system and training are needed to help HCPs engage in providing satisfactory sexual health care.