Highlights • 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.
In patients with rectal cancer, enlarged lateral lymph nodes (LLNs) result in increased lateral local recurrence (LLR) and lower cancer-specific survival (CSS) rates, which can be improved with ...(chemo)radiotherapy ((C)RT) and LLN dissection (LLND). This study investigated whether different LLN locations affect oncological outcomes.
Patients with low cT3-4 rectal cancer without synchronous distant metastases were included in this multicentre retrospective cohort study. All MRI was re-evaluated, with special attention to LLN involvement and response.
More advanced cT and cN category were associated with the occurrence of enlarged obturator nodes. Multivariable analyses showed that a node in the internal iliac compartment with a short-axis (SA) size of at least 7 mm on baseline MRI and over 4 mm after (C)RT was predictive of LLR, compared with a post-(C)RT SA of 4 mm or less (hazard ratio (HR) 5.74, 95 per cent c.i. 2.98 to 11.05 vs HR 1.40, 0.19 to 10.20; P < 0.001). Obturator LLNs with a SA larger than 6 mm after (C)RT were associated with a higher 5-year distant metastasis rate and lowered CSS in patients who did not undergo LLND. The survival difference was not present after LLND. Multivariable analyses found that only cT category (HR 2.22, 1.07 to 4.64; P = 0.033) and margin involvement (HR 2.95, 1.18 to 7.37; P = 0.021) independently predicted the development of metastatic disease.
Internal iliac LLN enlargement is associated with an increased LLR rate, whereas obturator nodes are associated with more advanced disease with increased distant metastasis and reduced CSS rates. LLND improves local control in persistent internal iliac nodes, and might have a role in controlling systemic spread in persistent obturator nodes.Members of the Lateral Node Study Consortium are co-authors of this study and are listed under the heading Collaborators.
Summary Background 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. Methods 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. Findings 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). Interpretation 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. Funding The Dutch Cancer Society, the Dutch National Health Council, and the Swedish Cancer Society.
Abstract Introduction Population-based data on metachronous peritoneal carcinomatosis (PC) after curative resection of colorectal origin are scarce. The aim of this study was to investigate the ...incidence of and risk factors for developing metachronous PC from colorectal cancer as well as survival since diagnosis of PC. Methods Data on metachronous metastases were collected between 2010 and 2011 for all patients diagnosed with M0 colorectal cancer between 2003 and 2008 in the Dutch Eindhoven Cancer Registry. Median follow-up was 5.0 years. Survival was defined as time from metastases diagnosis to death. Results Of the 5671 colorectal cancer patients, 1042 (18%) were diagnosed with metachronous metastases of whom 197 (19%) developed metachronous PC. The peritoneal surface was the only site of metastasis in 81 (41%) patients while 116 (59%) patients were diagnosed with both PC and metastases elsewhere. Median survival after diagnosis of PC was 6 months compared to 15 months for patients with distant metastases in other organs. Patients with an advanced primary tumour stage, positive lymph nodes at initial diagnosis, primary mucinous adenocarcinoma, positive resection margin and a primary tumour located in the colon were at increased risk of developing metachronous PC. Conclusion Of the colorectal cancer patients who developed metachronous metastases, approximately one fifth is diagnosed with PC. Prognosis of these patients is poor with a median survival of 6 months after diagnosis. Identifying patients at high risk for developing metachronous PC is important as it may contribute to more accurate patient information, tailor-made follow-up schemes, and more adequate treatment.
Most patients with locally recurrent breast cancer undergo axillary lymph node dissection (ALND). However, repeat sentinel node biopsy (SNB) could provide regional nodal staging and obviate the need ...for standard ALND. The Sentinel Node and Recurrent Breast Cancer (SNARB) study is a Dutch nationwide registration study conducted to determine feasibility, aberrant drainage rates, and clinical consequences of repeat SNB. A total of 536 patients with locally recurrent non-metastatic breast cancer underwent lymphatic mapping and repeat SNB in 29 Dutch hospitals. A repeat sentinel node (SN) was identified in 333 of 536 patients (62.1 %) and surgically harvested in 287 patients (53.5 %). Aberrant lymph drainage was observed in 180 (54.1 %) of the 333 patients, more often after previous ALND (81.9 %) than SNB (28.4 %;
P
< 0.001). In 230 patients (80.1 %), the retrieved SN was tumor negative; 17 SNs (5.9 %) contained a micrometastasis and 29 (10.1 %) a macrometastasis. Confirmation ALND in 31 repeat SN-negative patients revealed a macrometastasis in two patients (6.5 %). The negative predictive value (NPV) of repeat SNB was 93.6 %, and ALND was omitted in 109 of the 248 patients (44.0 %) with a negative repeat SN. In 29 of the 44 patients (63.0 %) with a positive SN, adjuvant treatment plans were altered based on the repeat SNB. Repeat SNB is a feasible procedure with a high NPV, leading to a change in management in a substantial proportion of patients. Therefore, repeat SNB should replace routine ALND and serve as the standard of care in recurrent breast cancer.
The results of the PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy regarding overall survival, disease-free survival, and ...recurrence rates after preoperative (chemo)radiotherapy and TME surgery in yp stage II and III rectal cancer patients.
The discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision (TME).
The PROCTOR-SCRIPT trial recruited patients from 52 hospitals. Patients with histologically proven stage II or III rectal adenocarcinoma were randomly assigned (1:1) to observation or adjuvant chemotherapy after preoperative (chemo)radiotherapy and TME. Radiotherapy consisted of 5 × 5 Gy. Chemoradiotherapy consisted of 25 × 1.8–2 Gy combined with 5-FU-based chemotherapy. Adjuvant chemotherapy consisted of 5-FU/LV (PROCTOR) or eight courses capecitabine (SCRIPT). Randomization was based on permuted blocks of six, stratified according to centre, residual tumour, time between last irradiation and surgery, and preoperative treatment. The primary end point was overall survival.
Of 470 enrolled patients, 437 were eligible. The trial closed prematurely because of slow patient accrual. Patients were randomly assigned to observation (n = 221) or adjuvant chemotherapy (n = 216). After a median follow-up of 5.0 years, 5-year overall survival was 79.2% in the observation group and 80.4% in the chemotherapy group hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.62–1.39;P = 0.73. The HR for disease-free survival was 0.80 (95% CI 0.60–1.07;P = 0.13). Five-year cumulative incidence for locoregional recurrences was 7.8% in both groups. Five-year cumulative incidence for distant recurrences was 38.5% and 34.7%, respectively (P = 0.39).
The PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy after preoperative (chemo)radiotherapy and TME on overall survival, disease-free survival, and recurrence rate. However, this trial did not complete planned accrual.
Dutch Colorectal Cancer group, CKTO 2003-16, ISRCTN36266738.
Background
This prospective multicentre study was performed to quantify the number of patients with minimal residual disease (ypT0–1) after neoadjuvant chemoradiotherapy and transanal endoscopic ...microsurgery (TEM) for rectal cancer.
Methods
Patients with clinically staged T1–3 N0 distal rectal cancer were treated with long‐course chemoradiotherapy. Clinical response was evaluated 6–8 weeks later and TEM performed. Total mesorectal excision was advocated in patients with residual disease (ypT2 or more).
Results
The clinical stage was cT1 N0 in ten patients, cT2 N0 in 29 and cT3 N0 in 16 patients. Chemoradiotherapy‐related complications of at least grade 3 occurred in 23 of 55 patients, with two deaths from toxicity, and two patients did not have TEM or major surgery. Among 47 patients who had TEM, ypT0–1 disease was found in 30, ypT0 N1 in one, ypT2 in 15 and ypT3 in one. Local recurrence developed in three of the nine patients with ypT2 tumours who declined further surgery. Postoperative complications grade I–IIIb occurred in 13 of 47 patients after TEM and in five of 12 after (completion) surgery. After a median follow‐up of 17 months, four local recurrences had developed overall, three in patients with ypT2 and one with ypT1 disease.
Conclusion
TEM after chemoradiotherapy enabled organ preservation in one‐half of the patients with rectal cancer.
Organ preservation feasible
Abstract Aim of the study In patients from the Dutch TME trial patterns of local recurrence (LR) in rectal cancer were studied. The purpose was to reconstruct the most likely mechanisms of LR and the ...effect of preoperative radiotherapy. Methods 1417 patients were analyzed; 713 were randomized into preoperative radiotherapy and total mesorectal excision (RT + TME), 704 into TME alone. Of the 114 patients with LR, the subsites of LR were determined and related to tumor and treatment factors. Results Overall 5-year LR-rate was 4.6% in the RT + TME group and 11.0% in the TME group. Presacral local recurrences occurred most in both groups. Radiotherapy reduced anastomotic LR significantly, except when after low anterior resection (LAR) distal margins were less than 5 mm. Abdominoperineal resection (APR) mainly resulted in presacral LR. Even after resection with a negative circumferential resection margin, LR-rates were high. Thirty percent of the patients had advanced tumors, which resulted in 58% of all LRs. Lateral LR comprised 20% of all LR. Presacral and lateral LR resulted in a poor prognosis, in contrast to anterior or anastomotic LRs with a relatively good prognosis. Conclusions RT reduces LR in all subsites and is especially effective in preventing anastomotic LR after LAR. APR-surgery mainly results in presacral LR, which may be prevented by a wider resection. In the TME trial many advanced tumors were included, rather requiring chemoradiotherapy instead of RT. Currently, with good imaging techniques, better selection can take place. Especially lateral LR might be a problem in the future.
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.
Summary 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.
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