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Beyond first-line palliative systemic treatment can be beneficial to selected oesophagogastric cancer patients, but experience with its administration may be limited and vary among hospitals. In a population-based study, we analysed the association between hospital systemic treatment volume and administration of beyond first-line treatment in oesophagogastric adenocarcinoma, as well as the effect on overall survival (OS). Synchronous metastatic oesophagogastric adenocarcinoma patients (2010–2017) were selected from the Netherlands Cancer Registry. Hospitals were categorised in volumes quartiles. The association between hospital systemic treatment volume and the use of beyond first-line treatment was assessed using trend and multivariable logistic regression analyses. OS was compared between hospitals with high and low beyond first-line treatment administration and treatment strategies using Kaplan–Meier curves with log-rank test and multivariable Cox proportional hazard regression. Beyond first-line treatment was administered in 606 of 2,466 patients who received first-line treatment, and increased from 20% to 31% between 2010 and 2017 (P < 0.001). The lowest hospital volumes were independently associated with lower beyond first-line treatment administration compared to the highest volume (OR 0.62, 95% CI 0.39–0.99; OR 0.67, 95% CI 0.48–0.95). Median OS was higher in all patients treated in hospitals with a high versus low beyond first-line treatment administration (7.9 versus 6.2 months, P < 0.001). Second-line paclitaxel/ramucirumab was administered most frequently and independently associated with longer OS compared to taxane monotherapy (HR 0.74, 95% CI 0.59–0.92). Higher hospital volume was associated with increased beyond first-line treatment administration in oesophagogastric adenocarcinoma. Second-line paclitaxel/ramucirumab resulted in longer survival compared to taxane monotherapy. • Beyond first-line treatment use in oesophagogastric cancer increased between 2010 and 2017. • Higher hospital volume is associated with increased beyond first-line treatment use. • Patients treated in high-volume beyond first-line treatment hospitals have better OS. • Second-line paclitaxel/ramucirumab resulted in longer OS than a taxane alone. [ABSTRACT FROM AUTHOR]

Background Young patients with rectal cancer tend to present with more advanced-stage disease and unfavourable tumour morphology. The effects of these tumour characteristics on survival in this particular patient group are unclear. Methods Population-based data from the Netherlands Cancer Registry (NCR) were used. Data from patients diagnosed with rectal cancer between 1989 and 2010 were selected. Younger patients (⩽40 years) were compared with middle-aged patients (41–70 years) with respect to disease stage, tumour characteristics, treatment and outcomes. Patients aged older than 70 years were excluded. Relative excess risk (RER) models were used to perform uni- and multivariate survival analyses. Findings A total of 37.056 patients were included (⩽40 years n = 1.102). Compared with middle-aged patients, young patients were more likely to have stage III (33.8% versus 27.8%) and stage IV (24.3% versus 19.6%) disease ( p < 0.001). Young patients also presented more frequently with mucinous tumours (10.8% versus 9.0%), signet cell carcinomas (2.6% versus 0.6%) and poorly differentiated tumours (16.6% versus 12.3%) ( p = 0.001). The treatment of stage I–III patients did not differ between the two groups, except regarding adjuvant chemotherapy, which was more often given to young patients (24.3% versus 14.4%, p < 0.001). Young age was a prognostic factor for better survival in stage I–III patients (RER 0.82 CI 0.71–0.94). Adjuvant chemotherapy was associated with improved survival in stage I–III patients (RER 0.76, 95%CI 0.70–0.83). In an exploratory analysis, adjuvant chemotherapy in young stage III and pN1 patients was associated with improved survival. Concluding statement Young patients present with more advanced disease and have more unfavourable tumour characteristics compared with middle-aged patients. Despite these characteristics, survival rates are equal, and young age is a prognostic factor for better survival. Although the use of adjuvant chemotherapy is controversial, a positive correlation with survival was found in this study. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Until recently, peritoneal metastases (PM) were regarded as an untreatable condition, regardless of the organ of origin. Currently, promising treatment options are available for selected patients with PM from colorectal, appendiceal, ovarian or gastric carcinoma. The aim of this study was to investigate the incidence, treatment and survival of patients presenting with PM in whom the origin of PM remains unknown. Methods: Data from patients diagnosed with PM of unknown origin during 1984–2010 were extracted from the Eindhoven Cancer Registry. European age-standardised incidence rates were calculated and data on treatment and survival were analysed. Results: In total 1051 patients were diagnosed with PM of unknown origin. In 606 patients (58%) the peritoneum was the only site of metastasis, and 445 patients also had other metastases. Chemotherapy usage has increased from 8% in the earliest period to 16% in most recent years (p =.016). Median survival was extremely poor with only 42days (95% confidence interval (CI) 39–47days) and did not change over time. Median survival of patients not receiving chemotherapy was significantly worse than of those receiving chemotherapy (36 versus 218days, p <.0001). Conclusion: The prognosis of PM of unknown origin is extremely poor and did not improve over time. Given the recent progress that has been achieved in selected patients presenting with PM, maximum efforts should be undertaken in order to diagnose the origin of PM as accurately as possible. Potentially effective treatment strategies should be further explored for patients in whom the organ of origin remains unknown. [Copyright &y& Elsevier]

Abstract: Background: The reported annual incidence of adrenocortical carcinoma (ACC) is 0.5–2.0 cases per million individuals. Updated population-based studies on incidence are lacking. The aim of this nationwide survey was to describe the incidence and survival rates of ACC in the Netherlands. Secondary objectives were to evaluate changes in both survival rates and the number of patients undergoing surgery. Methods: All ACC patients registered in the Netherlands Cancer Registry (NCR) between 1993 and 2010 were included. Data on demographics, stage of disease, primary treatment modality and survival were evaluated. Results: Included were 359 patients, 196 of whom were female (55%). Median age at diagnosis was 56years (range 1–91). The 5-year age-standardised incidence rate decreased from 1.3 to 1.0 per one million person-years. Median survival for patients with stage I–II, stage III and stage IV disease was 159months (95% confidence interval (CI) 93–225months), 26months (95% CI: 4–48months) and 5months (95% CI: 2–7months), respectively (P <0.001). Improvement in survival was not observed, as reflected by the lack of association between survival and time of diagnosis. The percentage of patients receiving treatment within 6months after diagnosis increased significantly from 76% in 1993–1998 to 88% in 2005–2010 (P =0.047), mainly due to an increase in surgery for stage III–IV patients. Conclusion: These nationwide data provide an up-to-date survey of the epidemiology of ACC in the Netherlands. A trend towards a decreasing overall incidence rate was observed. Survival rates did not change during this period despite an increased number of surgical procedures. [Copyright &y& Elsevier]

Although curative treatment options are identical for male and female gastroesophageal cancer patients, access to care and survival may vary. This study aimed to compare treatment allocation and survival between male and female patients with potentially curable gastroesophageal cancer. Nationwide cohort study including all patients with potentially curable gastroesophageal squamous cell or adenocarcinoma diagnosed between 2006 and 2018 registered in the Netherlands Cancer Registry. The main outcome, treatment allocation, was compared between male and female patients with oesophageal adenocarcinoma (EAC), oesophageal squamous cell carcinoma (ESCC), and gastric adenocarcinoma (GAC). Additionally, 5-year relative survival with relative excess risk (RER), that is, adjusted for the normal life expectancy, was compared. Among 27,496 patients (68.8% men), most were allocated to curative treatment (62.8%), although rates dropped to 45.6%>70 years. Curative treatment rates were comparable among younger male and female patients (≤70 years) with gastroesophageal adenocarcinoma, while older females with EAC were less frequently allocated to curative treatment than males (OR = 0.85, 95% confidence interval [CI] 0.73–0.99). For those allocated to curative treatment, relative survival was superior for female patients with EAC (RER = 0.88, 95% CI 0.80–0.96) and ESCC (RER = 0.82, 95% CI 0.75–0.91), and comparable for males and females with GAC (RER = 1.02, 95% CI 0.94–1.11). While curative treatment rates were comparable between younger male and female patients with gastroesophageal adenocarcinoma, treatment disparities were present between older patients. When treated, the survival of females with EAC and ESCC was superior to males. The treatment and survival gaps between male and female patients with gastroesophageal cancer warrant further exploration and could potentially improve treatment strategies and survival. • Nationwide study (n = 27,496) showing sex disparities in gastroesophageal cancer. • 63% of patients with potentially curative disease received treatment (♂ 64%, ♀ 59%). • Sex disparities in treatment allocation were mostly present for patients>70 years. • When treated, female patients with EAC and ESCC had superior survival. • The treatment and survival gaps between sexes warrant further consideration. [ABSTRACT FROM AUTHOR]

This population-based cohort study analysed treatment, overall survival (OS), and independent prognostic factors for OS in gastric cancer patients with liver metastases. Between 2015 and 2017, patients with synchronous metastatic gastric or gastroesophageal junction adenocarcinoma limited to the liver were included from the prospectively maintained population-based Netherlands Cancer Registry. Liver oligometastatic disease (OMD) was defined as ≤3 liver metastases. The primary outcome was OS. Independent prognostic factors for OS were analysed using multivariable Cox regression analysis. A total 295 patients with metastases limited to the liver were included. The primary tumour was resected in four patients (1.4%). Treatment for liver metastases consisted of chemotherapy alone (28.1%), trastuzumab plus chemotherapy (4.7%), surgery (1.0%), or best supportive care (67.5%). Median OS across all included patients was 4.0 months (95% confidence interval [CI]: 3.1–4.5). Liver OMD was detected in 77 patients (26%). Treatment for liver OMD consisted of chemotherapy alone (24.6%), trastuzumab plus chemotherapy (5.2%), surgery (3.9%), or best supportive care (67.5%). Median OS among patients with liver OMD was 5.7 months (95% CI: 4.8–7.5). Across all patients, better OS was independently associated with liver OMD (hazard ratio [HR] 0.66, 95% CI: 0.50–0.87), trastuzumab (HR 0.41, 95% CI: 0.23–0.72) but not with triplet compared with doublet chemotherapy (HR 0.94, 95% CI: 0.57–2.87). Worse OS was independently associated with unknown nodal stage versus cN0 (HR 1.74, 95% CI: 1.17–2.60), diffuse-type versus intestinal-type adenocarcinoma (HR 2.06, 95% CI: 1.32–3.20), and monotherapy or best supportive care versus doublet chemotherapy (HR 1.72, 95% CI: 1.03–2.87, and HR 3.61, 95% CI: 2.55–5.10, respectively). In this population-based cohort study, liver OMD was detected in 26% of patients. Liver OMD and trastuzumab treatment were independently associated with better OS while triplet as compared with doublet chemotherapy was not. OS among patients with liver OMD nevertheless remained poor. The concept of OMD and the benefit of resection of liver OMD may still have been relatively unknown in this disease type during the study inclusion years. [Display omitted] • 26% of patients with metastatic disease limited to the liver had liver OMD. • Liver OMD was independently associated with superior overall survival. • Overall survival in patients with liver OMD was nevertheless poor. [ABSTRACT FROM AUTHOR]

Population-based predictive factors for the effectiveness of second-line palliative systemic therapy in gastro-oesophageal cancer are not available. This study investigates the predictive value of effectiveness of first-line treatment for second-line treatment outcomes in gastro-oesophageal cancer in a real-world setting. Patients with metastatic gastro-oesophageal cancer diagnosed in 2010–2017 who were treated with second-line therapy after disease progression on first-line therapy were identified from the Netherlands Cancer Registry. Patients were divided into four groups as per duration of time to treatment failure (TTF) of the first line (0–3, 3–6, 6–9 and >9 months), and the association with overall survival (OS) and second-line TTF was assessed using Kaplan-Meier curves and two-sided multivariable regression models. Median OS since the start of the second line of patients (n = 611) with first-line TTF of 0–3, 3–6, 6–9 and >9 months was 4.0, 4.1, 5.5 and 7.1 months, respectively (P < 0.001). Median second-line TTF of patients with first-line TTF of 0–3, 3–6, 6–9 and >9 months was 2.8, 2.4, 3.0 and 4.5 months, respectively (P < 0.001). Patients with first-line TTF of >9 months showed a longer OS than patients with first-line TTF of 0–3 months (adjusted hazard ratio (HR) 1.90; 95% confidence interval (CI) 1.46–2.47), 3–6 months (adjusted HR 1.88; 95% CI 1.47–2.39) and 6–9 months (adjusted HR 1.31; 95% CI 1.04–1.65). Results for second-line TTF were similar. This study shows a positive correlation between effectiveness of first-line therapy and outcomes of second-line therapy in gastro-oesophageal cancer. Physicians should take duration of the first line into account when considering second-line palliative systemic therapy. • First-line time to treatment failure (TTF) is predictive for second-line TTF. • First-line TTF is predictive for second-line overall survival. • Clinicians should consider TTF when discussing the second line with patients. [ABSTRACT FROM AUTHOR]

The clinical significance of tumor-positive peritoneal cytology (CYT+) in gastric cancer (GC) patients is unclear. This nationwide cohort study aimed to i) assess the frequency of cytological analysis at staging laparoscopy; ii) determine the prevalence of CYT+GC; and iii) compare overall survival (OS) in CYT+ patients versus those with (PM+) and those without (PM-) macroscopic peritoneal disease. All patients diagnosed with cT1–4, cN0–2 and M0 or synchronous PM GC between 2016–2021 were identified in the Netherlands Cancer Registry database and linked to the nationwide pathology database. A total of 4397 patients was included, of which 40 % underwent cytological assessment following staging laparoscopy (863/1745). The prevalence of CYT+ was 8 %. A total of 69 patients had CYT+(1.6 %), 789 (17.9 %) had PM+ and 3539 (80.5 %) had PM- disease. Hazard ratio for OS in CYT+ versus PM+ was 0.86 (95 %CI 0.64–1.17, p-value=0.338), and in PM- versus PM+0.43 (95 %CI 0.38–0.49, p-value<0.001). No survival difference was found between systemic chemotherapy versus surgical resection in CYT+ patients. In this nationwide study, OS for gastric cancer patients with CYT+ was equally unfavorable as for those with PM+ and significantly worse as compared to those with PM-. The optimal treatment strategy has yet to be established. [Display omitted] • Tumor-positive peritoneal cytology and PM in GC had a comparable dismal survival. • Surgery and systemic treatment in CYT+ patients showed equal survival figures. • Staging laparoscopy including cytology improves patient selection for GC therapy. [ABSTRACT FROM AUTHOR]

Background Induction chemotherapy (IC) for clinically node-positive bladder cancer is applied without clinical evidence of improved outcome. Our objective was to compare complete pathological downstaging (pCD) and overall survival (OS) for IC versus upfront radical cystectomy (RC) in cT1-4aN1-3M0 urothelial carcinoma (UC). Methods This population-based study included 659 cN+ patients treated with RC between 1995 and 2013. IC was applied in 212 (32%) patients. We defined pCD as ≤(y)pT1N0 at RC. Multivariable analyses were preformed to identify independent predictors of pCD and OS. Results In cN1 and cN2–3 patients, 31% and 19% of patients proved to be pN0 at upfront RC. In cN1, pCD was achieved in 39% following IC versus 5% for upfront RC (P < 0.001). In cN2–3 UC, rates were 27% versus 3% (P < 0.001). Three-year OS for pCD and ypCD were 81% and 84%, respectively. Three-year OS rates were 66% versus 37% (cN1) and 43% versus 22% (cN2-3), again in favour of IC (P < 0.001). In multivariable analyses, IC was associated with pCD (Odds ratio, 14; 95% confidence interval [CI], 7.4–25) and a 53% decreased risk of death (Hazard ratio [HR], 0.47; 95% CI, 0.36–0.61). Indication bias and unequal distributions of factors associated with OS (e.g. patients proceeding to RC) limit interpretation of our results. Conclusions Patients with clinical nodal involvement should not be neglected. Up to 1/4 of patients with cN+ disease had pN0 at upfront RC. Moreover, IC followed by RC for clinically node-positive UC was associated with improved pathological downstaging compared with RC alone. A potential OS benefit for IC needs to be validated in a randomised trial. Take home message IC followed by RC for clinically node-positive UC is associated with improved pathological downstaging compared with RC alone. A potential OS benefit for IC needs to be validated in a randomised trial. [ABSTRACT FROM AUTHOR]

Abstract: Aim: For an evaluation of the progress achieved in the field of kidney cancer care in the Netherlands in the last decades, we described trends in incidence, treatment, mortality and relative survival. Methods: All adult patients newly diagnosed with kidney cancer between 1989 and 2009 (N =32,545) were selected from the Netherlands Cancer Registry. Age-standardised incidence and mortality rates were calculated. Follow-up was completed until January 2010. In order to assess trends estimated annual percentages of change (EAPC) were estimated. Results: The incidence of kidney cancer has been fairly stable between 1989 and 2001 with a European Standardised Rate of approximately 11 per 100,000 person years (PY). Since 2001 the incidence increased to 13 per 100,000 PY in 2009 (EAPC: 2.4%; 95%confidence interval (CI): 1.5 to 3.4%). The mortality rate decreased slightly over time, from 6.2 per 100,000 PY in 1989 to 5.6 in 2010. No changes in treatment were observed, except for the introduction of targeted therapies for stage IV disease, since 2005. The 5-year relative survival improved from 51% in 1989–1994 to 58% in 2005–2009 (EAPC: 0.9%; 95%CI 0.7 to 1.2%). Improvement in survival was especially seen in males, younger age groups and low stages. Conclusions: The incidence of kidney cancer has increased slightly, and survival improved modestly, resulting in a decreasing mortality. A positive effect of the introduction of targeted therapies for metastatic kidney cancer was observed in 1-year relative survival. For progress in kidney cancer care, effective prevention strategies and new therapies remain warranted. [Copyright &y& Elsevier]