Peritoneal metastases from gastric cancer in a nationwide cohort: Incidence, treatment and survival.

The aims of this study were to investigate incidence, risk factors and treatment of synchronous or metachronous peritoneal metastases (PM) from gastric cancer and to estimate survival of these patients using population-based data. Patients diagnosed with gastric cancer in 2015 to 2016 were selected from the Netherlands Cancer Registry. The incidence of synchronous and metachronous PM were calculated. Multivariable regression analyses were performed to identify factors associated with the occurrence of PM. Treatment and survival were compared between patients with synchronous and metachronous PM. Of 2206 patients with gastric cancer, 741 (34%) were diagnosed with PM. Of these, 498 (23%) had synchronous PM. The cumulative incidence of metachronous PM in patients who underwent potentially curative treatment (n = 675) was 22.8% at 3 years. A factor associated with synchronous and metachronous PM was diffuse type histology. Patients diagnosed with synchronous PM more often received systemic treatment than patients with metachronous PM (35% vs 18%, respectively, P < .001). Median overall survival was comparable between synchronous and metachronous PM (3.2 vs 2.3 months, respectively, P = .731). Approximately one third of all patients with gastric cancer are diagnosed with PM, either at primary diagnosis or during 3-year follow-up after potentially curative treatment. Patients with metachronous PM less often received systemic treatment than those with synchronous PM but survival was comparable between both groups. Future trials are warranted to detect gastric cancer at an earlier stage and to examine strategies that lower the risk of peritoneal dissemination. Also, specific treatment options for patients with gastric PM should be further investigated.

The impact of an open or laparoscopic approach on the development of metachronous peritoneal metastases after primary resection of colorectal cancer: results from a population-based cohort study.

BACKGROUND: This study aimed to assess the impact of open or laparoscopic resection of primary colorectal cancer (CRC) on the development of metachronous colorectal peritoneal metastases (CPM) in a population-based cohort. MATERIALS AND METHODS: This was a retrospective, population-based study of CRC patients who underwent open or laparoscopic resection of the primary tumour in the Netherlands between January 1st and June 30th 2015. Patients with synchronous metastases were excluded. CPM were considered metachronous if diagnosed ≥ 90 days after resection of primary CRC. Multivariable cox regression analysis was performed to correct for tumour location, histology, differentiation, and stage, nodal stage, tumour perforation, primary surgery type, and unclear resection margins. RESULTS: In total, 1516 CRC patients underwent open resection and 3236 CRC patients underwent laparoscopic resection, with a 3-year cumulative incidence of metachronous CPM of 7.3% and 3.7%, respectively (p < 0.001), after median follow-up of 42 months. Open surgical approach was significantly associated with the development of metachronous CPM: HR 1.4 [95%CI 1.1-1.8]. Other prognostic factors were mucinous adenocarcinoma histology (HR 1.6, 95%CI 1.0-2.5), T4 stage (HR 3.2, 95%CI 2.3-4.5), N1 stage (HR 2.9, 95%CI 2.1-4.0), and N2 stage (HR 4.2, 95%CI 2.9-6.1). CONCLUSIONS: Patients treated with open resection had a significantly higher risk to develop metachronous CPM than patients treated with laparoscopic resection. The mechanisms underlying this phenomenon remain unknown but might be related to differences in per-operative specimen handling, tumour spill, surgical trauma and pro-inflammatory response. This finding might imply the need for a personalized follow-up after primary resection of CRC.

Peritoneal Metastases from Extraperitoneal Primary Tumors: Incidence, Treatment, and Survival from a Nationwide Database.

The objective of this study was to assess the incidence, treatment, and survival of patients with synchronous peritoneal metastases (PM) from extraperitoneal primary tumors. A cohort was selected from the Netherlands Cancer Registry (NCR), in which all patients diagnosed with PM in 2017 and 2018 were screened for eligibility. The five most common primary extraperitoneal origins of PM were included for further analyses: lung, breast, urinary tract, and kidney cancer and malignant melanoma. Survival was investigated using log-rank test between different primary tumor locations. In total, 480 patients were diagnosed with synchronous PM from extraperitoneal origins. The proportion of patients with PM per extraperitoneal origin ranged between 0.1 and 1.1%, with the highest proportion in lung cancer patients. Of all patients, 234 (49%) received tumor-directed treatment and 246 (51%) received no tumor-directed treatment. Survival in patients with PM from lung, breast, urinary tract, and kidney cancer and malignant melanoma was 1.6 months, 15.7 months, 5.4 months, 3.4 months, and 2.1 months, respectively (p < 0.001). In this study, a small, although significant number of patients with extraperitoneal cancer developed PM. The reported survival in patients with PM ranged between 1.6 and 15.7 months. Only half of the patients with PM received tumor-directed treatment and survival in patients without tumor-directed treatment was only 1.2 months. These findings are stressing the need to explore new diagnostic tools that may enable earlier diagnosis of PM and may potentially lead to a more effective treatment.

Updated Incidence, Treatment and Survival of a Nationwide Cohort of Patients with Peritoneal Metastases of Unknown Origin.

The aim of this study was to investigate the incidence, treatment and survival of patients with peritoneal metastases (PM) of unknown origin. All Dutch patients diagnosed in 2017 and 2018 with PM of unknown origin (PM-CUP) were evaluated. Data were extracted from the Netherlands Cancer Registry (NCR). Patients with PM-CUP were categorized into the following histological subtypes: 1) adenocarcinoma, 2) mucinous adenocarcinoma, 3) carcinoid, 4) unspecified carcinoma and 5) other. Treatments were compared between the different histological subtypes in patients with PM-CUP. Overall survival (OS) was calculated using the Kaplan-Meier method for all patients with cancer of unknown origin and between histological subtypes in patients with PM-CUP. Significant differences in OS were assessed by using the log-rank test. In total, 3026 patients were diagnosed with cancer of unknown origin, 513 (17%) among them were diagnosed with PM-CUP. Most PM-CUP patients received best supportive care only (76%), whereas 22% received systemic treatment and 4% underwent metastasectomy. Median OS was 1.1 months for all patients with PM-CUP but varied from 0.6 months to 30.5 months depending on the underlying histology. In this study, PM-CUP were diagnosed in 17% of all patients with cancer of unknown primary and the reported survival in this cohort was extremely poor. Since survival differed among histological subtypes and recently more treatment options became available for a selected group of patients with peritoneal malignancies, it is of great importance to identify the histology of the metastases and whenever possible the primary tumor.

Primary tumor resection or systemic treatment as palliative treatment for patients with isolated synchronous colorectal cancer peritoneal metastases in a nationwide cohort study.

Limited data are available to guide the decision-making process for clinicians and their patients regarding palliative treatment options for patients with isolated synchronous colorectal cancer peritoneal metastases (CRC-PM). Therefore, the aim of this study is to analyze the outcome of the different palliative treatments for these patients. All patients diagnosed with isolated synchronous CRC-PM between 2009 and 2020 (Netherlands Cancer Registry) who underwent palliative treatment were included. Patients who underwent emergency surgery or curative intent treatment were excluded. Patients were categorized into upfront palliative primary tumor resection (with or without additional systemic treatment) or palliative systemic treatment only. Overall survival (OS) was compared between both groups and multivariable cox regression analysis was performed. Of 1031 included patients, 364 (35%) patients underwent primary tumor resection and 667 (65%) patients received systemic treatment only. Sixty-day mortality was 9% in the primary tumor resection group and 5% in the systemic treatment group (P = 0.007). OS was 13.8 months in the primary tumor resection group and 10.3 months in the systemic treatment group (P < 0.001). Multivariable analysis showed that primary tumor resection was associated with improved OS (HR 0.68; 95%CI 0.57-0.81; P < 0.001). Palliative primary tumor resection appeared to be associated with improved survival compared to palliative systemic treatment alone in patients with isolated synchronous CRC-PM despite a higher 60-day mortality. This finding must be interpreted with care as residual bias probably played a significant role. Nevertheless, this option may be considered in the decision-making process by clinicians and their patients.

Insights into synchronous peritoneal metastases from hepatobiliary origin: Incidence, risk factors, treatment, and survival from a nationwide database.

INTRODUCTION: - This population-based study aimed to investigate incidence, risk factors, treatment, and survival of synchronous peritoneal metastases (PM) of hepatobiliary origin. METHODS: - All Dutch patients diagnosed with hepatobiliary cancer between 2009 and 2018 were selected. Factors associated with PM were identified with logistic regression analyses. Treatments for patients with PM were categorized into local therapy, systemic therapy, and best supportive care (BSC). Overall survival (OS) was investigated using log-rank test. RESULTS: - In total, 12 649 patients were diagnosed with hepatobiliary cancer of whom 8% (n = 1066) were diagnosed with synchronous PM (12% [n = 882/6519] in biliary tract cancer [BTC] vs. 4% [n = 184/5248] in hepatocellular carcinoma [HCC]). Factors that were positively associated with PM were the female sex (OR 1.18, 95% CI 1.03-1.35), BTC (OR 2.93, 95% CI 2.46-3.50), diagnosis in more recent years (2013-2015: OR 1.42, 95% CI 1.20-1.68; 2016-2018: OR 1.48, 95% CI 1.26-1.75), T3/T4 stage (OR 1.84, 95% CI 1.55-2.18), N1/N2 stage (OR 1.31, 95% CI 1.12-1.53) and other synchronous systemic metastases (OR 1.85, 95% CI 1.62-2.12). Of all PM patients, 723 (68%) received BSC only. Median OS was 2.7 months (IQR 0.9-8.2) in PM patients. CONCLUSION: - Synchronous PM were found in 8% of all hepatobiliary cancer patients and occurred more often in BTC than in HCC. Most patients with PM received BSC only. Given the high incidence and dismal prognosis of PM patients, extended research in hepatobiliary PM is needed to achieve better outcome in these patients.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy with Intra-Operative Radiotherapy for Patients with Locally Advanced or Locally Recurrent Rectal Cancer and Peritoneal Metastases.

Purpose: To assess the safety and long-term outcome of a multimodality treatment consisting of radical surgery, intra-operative radiotherapy (IORT), and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for patients with locally advanced rectal cancer (LARC) or locally recurrent rectal carcinoma (LRRC) and peritoneal metastases (PM). Methods: The present study was a single-center cohort study, including all consecutive patients undergoing this treatment in a tertiary referral center for LARC, LRRC, and PM. Postoperative complications, intensive care stay (ICU stay), and re-admission rates were assessed as well as disease-free survival (DFS) and overall survival (OS). Results: A total of 14 LARC and 16 LRRC patients with PM were included in the study. The median ICU stay was 1 day, and 57% of patients developed a severe postoperative complication. No 90-day mortality was observed. Median DFS was 10.0 months (Interquartile Range 7.1-38.7), and median OS was 31.0 months (Interquartile Range 15.9-144.3). Conclusions: As postoperative complications and survival were in line with treatments that are accepted for LARC or LRRC and PM as separate procedures, we conclude that combined treatment with IORT and CRS-HIPEC should be considered as a treatment option for selected patients with LARC or LRRC and peritoneal metastases in tertiary referral centers.

The Burden of Peritoneal Metastases from Gastric Cancer: A Systematic Review on the Incidence, Risk Factors and Survival.

The peritoneum is a common metastatic site in gastric cancer. This systematic review provides an overview of the incidence, risk factors and survival of synchronous peritoneal metastases from gastric cancer. A systematic search was performed to identify studies wherein the incidence, risk factors and survival of gastric cancer with peritoneal metastases were investigated. Of all 38 potentially eligible studies, 17 studies were included based on the eligibility criteria. The incidence of synchronous gastric peritoneal metastases was reviewed for population-based studies (10-21%), for observational cohort studies (2-15%) and for surgical cohort studies (13-40%). Potential risk factors for synchronous gastric peritoneal metastases were younger age, non-cardia gastric cancer, female sex, signet ring cell carcinoma, diffuse type histology or linitis plastica, T4 stage, Hispanic ethnicity and more than one metastatic location. Synchronous peritoneal metastases are commonly diagnosed in patients with gastric cancer with an incidence up to 21% in recent population-based studies. Furthermore, prognosis of patients with gastric peritoneal metastases is poor with median overall survival ranging from 2 to 9 months. The high incidence and poor prognosis require intensive research on diagnostic features and effective treatment options to improve survival.

Incidence, Treatment, and Survival of Synchronous Peritoneal Metastases in Pancreatic Cancer: Update of a Nationwide Cohort.

OBJECTIVE: The aim of the study was to gain insight in the incidence, treatment, and survival of patients with synchronous pancreatic peritoneal metastases. METHODS: All patients diagnosed with pancreatic cancer between 2008 and 2018 in the Netherlands Cancer Registry were evaluated. The patients were subcategorized as (1) synchronous peritoneal metastases, (2) synchronous systemic metastases, and (3) no metastases. RESULTS: In total, 25,334 patients with pancreatic cancer were included. Among them, 3524 (14%) presented with synchronous peritoneal metastases, 10,659 (42%) with systemic metastases, and 11,151 (44%) without metastases at the time of diagnosis. The proportion of the patients diagnosed with peritoneal metastases increased over time (11%, 2008; 16%, 2018; P < 0.001). Of these patients, 964 (27%) received cancer treatment and 2560 (73%) received best supportive care. The median overall survival in patients with peritoneal metastases, systemic metastases, and without metastases was 1.9, 2.4, and 8.0 months, respectively (P < 0.001). In the patients with peritoneal metastases, the median overall survival was 5.0 months when undergoing cancer treatment and 1.3 months with best supportive care (P < 0.001). CONCLUSIONS: Patients with pancreatic cancer are increasingly diagnosed with synchronous peritoneal metastases. Given the current dismal prognosis, research to improve treatment is designated for this patient category.

Synchronous peritoneal metastases from lung cancer: incidence, associated factors, treatment and survival: a Dutch population-based study.

Peritoneal metastases (PM) from lung cancer are rare and it is unknown how they affect the prognosis of patients with lung cancer. This population-based study aimed to assess the incidence, associated factors, treatment and prognosis of PM from lung cancer. Data from the Netherlands Cancer Registry were used. All patients diagnosed with lung cancer between 2008 and 2018 were included. Logistic regression analysis was performed to identify factors associated with the presence of PM. Cox regression analysis was performed to identify factors associated with the overall survival (OS) of patients with PM. Between 2008 and 2018, 129,651 patients were diagnosed with lung cancer, of whom 2533 (2.0%) patients were diagnosed with PM. The European Standardized Rate of PM increased significantly from 0.6 in 2008 to 1.4 in 2018 (p < 0.001). Age between 50 and 74 years, T3-4 tumour stage, N2-3 nodal stage, tumour morphology of a small cell lung cancer or adenocarcinoma, and the presence of systemic metastases were associated with the presence of PM. The median OS of patients with PM was 2.5 months. Older age, male sex, T3-4 tumour stage, N2-3 nodal stage, not receiving systemic treatment, and the presence of systemic metastases were associated with a worse OS. Synchronous PM were diagnosed in 2.0% of patients with lung cancer and resulted in a very poor survival.