Novel Prognostic Staging System for Patients With De Novo Metastatic Breast Cancer.

PURPOSE: Given the heterogeneity and improvement in outcomes for metastatic breast cancer (MBC), we developed a staging system that refines prognostic estimates for patients with metastatic cancer at the time of initial diagnosis, de novo MBC (dnMBC), on the basis of survival outcomes and disease-related variables. METHODS: Patients with dnMBC (2010-2016) were selected from the National Cancer Database (NCDB). Recursive partitioning analysis (RPA) was used to group patients with similar overall survival (OS) on the basis of clinical T category, grade, estrogen receptor (ER), progesterone receptor, human epidermal growth factor receptor 2, histology, organ system site of metastases (bone-only, brain-only, visceral), and number of organ systems involved. Three-year OS rates were used to assign a final stage: IVA: >70%, IVB: 50%-70%, IVC: 25 to <50%, and IVD: <25%. Bootstrapping was applied with 1,000 iterations, and final stage assignments were made based on the most commonly occurring assignment. Unadjusted OS was estimated. Validation analyses were conducted using SEER and NCDB. RESULTS: At a median follow-up of 52.9 months, the median OS of the original cohort (N = 42,467) was 35.4 months (95% CI, 34.8 to 35.9). RPA stratified patients into 53 groups with 3-year OS rates ranging from 73.5% to 5.7%; these groups were amalgamated into four stage groups: 3-year OS, A = 73.2%, B = 61.9%, C = 40.1%, and D = 17% (log-rank P < .001). After bootstrapping, the survival outcomes for the four stages remained significantly different (log-rank P < .001). This staging system was then validated using SEER data (N = 20,469) and a separate cohort from the NCDB (N = 7,645) (both log-rank P < .001). CONCLUSION: Our findings regarding the heterogeneity in outcomes for patients with dnMBC could guide future revisions of the current American Joint Committee on Cancer staging guidelines for patients with newly diagnosed stage IV disease. Our findings should be independently confirmed.

The survival gap between young and older patients after surgical resection for colorectal cancer remains largely based on early mortality: A EURECCA comparison of four European countries.

BACKGROUND: A decade ago, it was demonstrated that the difference in survival between older patients and younger patients with colorectal cancer (CRC) was mainly due to mortality in the first postoperative year. Over the last few years, improvements - especially in perioperative care - have increased survival. The current research investigates whether a survival gap between younger and older patients with CRC still exists on a national level in four European countries. METHODS: Population-based data from Belgium, the Netherlands, Norway, and Sweden were collected from patients that underwent surgical resection for primary stage I-III CRC between 2007 and 2016. Relative survival and conditional relative survival (CS), with the condition of surviving the first postoperative year, were calculated for colon and rectal cancer separately, stratified for country and age category (<65, 65-75, ≥75 years). In addition, relative excess risk of death (RER) was estimated, and one-year excess mortality was calculated. RESULTS: Data of 206,024 patients were analyzed. In general, compared to patients <65 years, patients ≥75 years had a worse survival during the first year after surgery, which was most pronounced in Belgium (RER colon cancer 2.5 [95% confidence interval (CI) 2.3-2.8] and RER rectal cancer 2.6 [95% CI 2.3-2.9]). After surviving the first year, CS was mostly not statistically different between patients <65 years and patients ≥75 years with stage I-II, with the exception of stage II colon cancer in Belgium. However, CS remained worse in the largest part of the patients ≥75 years with stage III colon or rectal cancer (except for rectal cancer in Norway). CONCLUSIONS: Although differences exist between the countries, the survival gap between young and older patients is based mainly on early mortality and remains only for stage III disease after surviving the first year.

Development and external validation of a prediction model for overall survival after resection of distal cholangiocarcinoma.

BACKGROUND: Various prognostic factors are associated with overall survival (OS) after resection of distal cholangiocarcinoma (dCCA). The objective of this study was to develop and validate a prediction model for 3-year OS after pancreatoduodenectomy for dCCA. METHODS: The derivation cohort consisted of all patients who underwent pancreatoduodenectomy for dCCA in the Netherlands (2009-2016). Clinically relevant variables were selected based on the Akaike information criterion using a multivariate Cox proportional hazards regression model, with model performance being assessed by concordance index (C-index) and calibration plots. External validation was performed using patients from the Belgium Cancer Registry (2008-2016), and patients from two university hospitals of Southampton (U.K.) and Verona (Italy). RESULTS: Independent prognostic factors for OS in the derivation cohort of 454 patients after pancreatoduodenectomy for dCCA were age (HR 1.02, 95% CI 1.01-1.03), pT (HR 1.43, 95% CI 1.07-1.90) and pN category (pN1: HR 1.78, 95% CI 1.37-2.32; pN2: HR 2.21, 95% CI 1.63-3.01), resection margin status (HR 1.79, 95% CI 1.39-2.29) and tumour differentiation (HR 2.02, 95% CI 1.62-2.53). The prediction model was based on these prognostic factors. The optimism-adjusted C-indices were similar in the derivation cohort (0.69), and in the Belgian (0.66) and Southampton-Verona (0.68) validation cohorts. Calibration was accurate in the Belgian validation cohort (slope = 0.93, intercept = 0.12), but slightly less optimal in the Southampton-Verona validation cohort (slope = 0.88, intercept = 0.32). Based on this model, three risk groups with different prognoses were identified (3-year OS of 65.4%, 33.2% and 11.8%). CONCLUSIONS: The prediction model for 3-year OS after resection of dCCA had reasonable performance in both the derivation and geographically external validation cohort. Calibration slightly differed between validation cohorts. The model is readily available via www. pancreascalculator.com to inform patients from Western European countries on their prognosis, and may be used to stratify patients for clinical trials.

One-year excess mortality and treatment in surgically treated patients with colorectal cancer: A EURECCA European comparison.

BACKGROUND: Mortality in the first postoperative year represents an accurate reflection of the perioperative risk after colorectal cancer surgery. This research compares one-year mortality after surgery divided into three age-categories (18-64, 65-74, ≥75 years), focusing on time trends and comparing treatment strategies. MATERIAL: Population-based data of all patients diagnosed and treated surgically for stage I-III primary colorectal cancer from 2007 to 2016, were collected from Belgium, the Netherlands, Norway, and Sweden. Stratified for age-category and stage, treatment was evaluated, and 30-day, one-year and one-year excess mortality were calculated for colon and rectal cancer separately. Results were evaluated over two-year time periods. RESULTS: Data of 206,024 patients were analysed. Postoperative 30-day and one-year mortality reduced significantly over time in all countries and age-categories. Within the oldest age category, in 2015-2016, one-year excess mortality varied from 9% in Belgium to 4% in Sweden for colon cancer and, from 9% in Belgium to 3% in the other countries for rectal cancer. With increasing age, patients were less likely to receive additional therapy besides surgery. In Belgium, colon cancer patients were more often treated with adjuvant chemotherapy (p < 0.001). For neoadjuvant treatment of rectal cancer, patients in Belgium and Norway were mostly treated with chemoradiotherapy. In the Netherlands and Sweden, radiotherapy alone was preferred (p < 0.001). CONCLUSIONS: Despite improvement over time in all countries and age-categories, substantial variation exists in one-year postoperative mortality. Differences in one-year excess postoperative mortality could be due to differences in treatment strategies, highlighting the consequences of under- and over-treatment on cancer survival.

Skin melanoma deaths within 1 or 3 years from diagnosis in Europe.

The steep increase in incidence of cutaneous malignant melanoma in white populations mainly applies to thin lesions with good survival suggesting overdiagnosis. Based on population-based cancer registries (CRs), we have investigated changes in aggressive melanoma, selecting only cases who died within 1 or 3 years after diagnosis in 11 European countries between 1995 and 2012. Trends in fatal cases were analysed by period of diagnosis, sex, tumour thickness, histologic subtype of the lesion, tumour site and CR with a multivariate generalised linear mixed effects model, where geographical area was considered as a random effect. We collected data on 123 360 invasive melanomas, with 5133 fatal cases at 1 year (4%) and 12 330 (10%) at 3 years. The number of fatal cases showed a 16% decrease at 1 year and 8% at 3 years between the first (1995-2000) and the last (2007-2012) period. The highest proportion of fatal cases was seen for men, older age (≥65 years), thick lesions (>1 mm), nodular melanoma, melanoma on the trunk and for poorly documented cases, lacking information about thickness and histologic subtype. The mixed-effects model showed a remarkable variability among European countries. The majority of registries showed a decreasing trend in fatal cases, but a few registries showed an opposite pattern. Trends in fatal melanoma cases, highlighting real changes in risk not related to overdiagnosis, showed a decrease in most European countries, with a few exceptions. Stronger efforts for early detection could lead to a more efficient treatment of melanoma in general.

Variation in adjuvant and early salvage radiotherapy after robot-assisted radical prostatectomy for prostate cancer: a population-based cohort study.

Purpose: The primary aim of the study was to assess the association between having a radiotherapy (RT) department on-site at the surgical centre and the performed postoperative treatment strategy for prostate cancer (PCa) patients. According to the current international guidelines, adjuvant radiotherapy (ART) or a regular prostate-specific antigen (PSA)-based follow-up with (early) salvage radiotherapy ((e)SRT) if needed is recommended in case of adverse pathological characteristics.Material and methods: Prospective data on consecutive robot-assisted radical prostatectomy (RARP) patients in Belgium from 2009 to 2016 were identified in the Belgian Robotic-Assisted-Laparoscopic-Prostatectomy (Be-RALP) database. Multivariable regression was used to evaluate patient- and facility-related factors associated with postoperative radiation treatment.Results: 2072 patients undergoing a RARP, suffering at least one of the following adverse pathological features, i.e., extracapsular extension (ECE), seminal vesicle invasion (SVI) or positive section margins (PSM), and with registered follow-up until 24 months were enrolled. After RARP, ART was applied to 9.1% and (e)SRT to 12.6% of the patients. Multivariable analysis demonstrated that patients were more likely to receive ART or (e)SRT if they were operated in a hospital with a RT department on-site (odds ratio, ART: 1.49 [1.07-2.07]; (e)SRT: 1.55 [1.16-2.06]). Furthermore, the presence of higher tumour category (T-category) and/or PSM on final pathology was associated with a higher chance of getting ART and (e)SRT (p < .01).Conclusion: Variations in ART and (e)SRT are not only driven by patient-related characteristics. In our nationwide cohort, the availability of a RT department on-site at the surgical centre was found to be an independent predictor for ART and (e)SRT, with a 1.5 times higher odds of receiving postoperative RT during the first 24 months after surgery.

Treatment and Survival of Elderly Patients with Stage I-II Pancreatic Cancer: A Report of the EURECCA Pancreas Consortium.

BACKGROUND: Elderly patients with pancreatic cancer are underrepresented in clinical trials, resulting in a lack of evidence. OBJECTIVE: The aim of this study was to compare treatment and overall survival (OS) of patients aged ≥ 70 years with stage I-II pancreatic cancer in the EURECCA Pancreas Consortium. METHODS: This was an observational cohort study of the Belgian (BE), Dutch (NL), and Norwegian (NOR) cancer registries. The primary outcome was OS, while secondary outcomes were resection, 90-day mortality after resection, and (neo)adjuvant and palliative chemotherapy. RESULTS: In total, 3624 patients were included. Resection (BE: 50.2%; NL: 36.2%; NOR: 41.3%; p < 0.001), use of (neo)adjuvant chemotherapy (BE: 55.9%; NL: 41.9%; NOR: 13.8%; p < 0.001), palliative chemotherapy (BE: 39.5%; NL: 6.0%; NOR: 15.7%; p < 0.001), and 90-day mortality differed (BE: 11.7%; NL: 8.0%; NOR: 5.2%; p < 0.001). Furthermore, median OS in patients with (BE: 17.4; NL: 15.9; NOR: 25.4 months; p < 0.001) and without resection (BE: 7.0; NL: 3.9; NOR: 6.5 months; p < 0.001) also differed. CONCLUSIONS: Differences were observed in treatment and OS in patients aged ≥ 70 years with stage I-II pancreatic cancer, between the population-based cancer registries. Future studies should focus on selection criteria for (non)surgical treatment in older patients so that clinicians can tailor treatment.

Head and Neck Cancer in Belgium: Quality of Diagnostic Management and Variability Across Belgian Hospitals Between 2009 and 2014.

Aims: The study assessed the quality of diagnosis and staging offered to patients with a head and neck squamous cell carcinoma (HNSCC) and the variability across Belgian hospitals. Methods: In total, 9,245 patients diagnosed with HNSCC between 2009 and 2014, were identified in the population-based Belgian Cancer Registry (BCR). The BCR data were coupled with other databases providing information on diagnostic and therapeutic procedures reimbursed by the compulsory health insurance, vital status data, and comorbidities. The use of diagnosis and staging procedures was assessed by four quality indicators (QI) (i.e., use of dedicated head and neck imaging studies, use of PET-CT, TNM reporting and interval between diagnosis and start of treatment), for which a target was defined before the analysis. The association between the binary QIs and observed survival was assessed using Cox proportional hazard models adjusted for potential confounders. Results: Overall, 82.5% of patients received staging by MRI and/or CT of the head and neck region before the start of treatment. In 47.6% of stage III-IV patients eligible for treatment with curative intent, a whole-body FDG-PET(/CT) was performed. The proportion of patients whose cTNM and pTNM stage was reported to the BCR was 80.5 and 78.4%, respectively. The median interval from diagnosis to first treatment with curative intent was 32 days (IQR: 19-46). For none of these QIs the pre-set targets were reached and a substantial variability between centers was observed for all quality indicators. No binary QI was significantly associated with observed survival. Conclusions: The four quality indicators related to diagnosis and staging in HNSCC all showed substantial room for improvement. For none of them the pre-set targets were met at the national level and the variability between centers was substantial. Each Belgian hospital received an individual feedback report in order to stimulate reflection and quality improvement processes.

Association between surgical volume and post-operative mortality and survival after surgical resection in lung cancer in Belgium: A population-based study.

OBJECTIVES: The existence of a relationship between hospital surgical volume and outcome after lung cancer surgery remains an ongoing debate. We aimed to evaluate the association between volume and 60-day mortality, 1- and 3-year observed survival (OS) in non-small cell lung cancer (NSCLC) patients in Belgium. METHODS: Patients diagnosed with NSCLC in 2010-2011 were identified in the database of the Belgian Cancer Registry, excluding patients with multiple tumours. Regression models were applied to assess the relationship between hospital surgical volume, 60-day mortality and 1- and 3-year OS, adjusting for different patient and tumour characteristics. Surgical volume was taken into account as a continuous variable in the models. RESULTS: In 2010-2011 a total of 9,817 patients with NSCLC were diagnosed in Belgium and 2,084 of them underwent surgery. After adjusting for patient and tumour characteristics, a relationship between hospital surgical volume and patients' outcome was found. Postoperative mortality and survival improved with increasing annual surgical volume up to 10 interventions. However, no further gain in outcome has been observed above 10. While the 60-day postoperative mortality is 3.5% for hospitals with an annual volume larger than 10, the predicted mortality rate for a hospital with an annual volume of only 5 interventions is 6.5%. Similar results were observed for 1- and 3-year OS. CONCLUSION: In Belgium, a higher hospital surgical volume is associated with improved outcome in NSCLC patients after surgical resection. Minimally 10 surgical interventions per year seem to be required to achieve an optimal performance.

Current Management of pT3b Prostate Cancer After Robot-assisted Laparoscopic Prostatectomy.

BACKGROUND: Robot-assisted radical prostatectomy (RALP) in high-risk and locally advanced prostate cancer (PCa) is gaining increasing traction. The optimal use of additional treatments for PCa with seminal vesicle invasion (pT3b) after RALP remains ill explored. OBJECTIVE: To evaluate the management of pT3b PCa after RALP in current clinical practice. DESIGN, SETTING, AND PARTICIPANTS: As part of the prospective Belgian RALP Consortium project (October 2009-March 2016), 796 patients with pT3b disease were evaluated. INTERVENTION: Robot-assisted radical prostatectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Population and perioperative characteristics were described to assess surgical outcome. Multivariable regression analyses were used to identify independent predictors of lymph node invasion (pN1), positive surgical margins (R+), postoperative morbidity, and additional treatments. RESULTS AND LIMITATIONS: In this prospective population-based registry, 85% of patients with clinical high-risk locally advanced PCa received pelvic lymph node dissection (PLND). Early postoperative complications (0-30 d) were observed in 68 patients (8.5%). During oncologic follow-up (median 12 mo), 63% of pN1 patients and 56% of R+ patients received additional therapy. Performing PLND (necessary for assessing pN1 status) was a specific predictor for androgen deprivation therapy only, whereas R+ and younger age were independent predictors for radiotherapy only. Limitations include the nonstandardized policy on additional treatments among hospitals. CONCLUSIONS: In current practice, RALP is performed with acceptable morbidity for PCa with seminal vesicle invasion and the use of postoperative additional treatments is influenced by different patient, tumor, and surgical variables. Despite the recommendations, 15-21% of patients do not receive adequate pelvic lymph node staging and adjuvant therapy is given in 38% of patients. Full and correct staging of the real disease extent remains important in the management of these patients. PATIENT SUMMARY: This study on prostate cancer with seminal vesicle invasion after robot-assisted prostatectomy evaluates the use of additional treatments in current clinical practice. Additional treatments for advanced prostate cancer should be patient-adjusted according to the disease extent.

Treatment and survival of rectal cancer patients over the age of 80 years: a EURECCA international comparison.

BACKGROUND: The optimal treatment strategy for older rectal cancer patients remains unclear. The current study aimed to compare treatment and survival of rectal cancer patients aged 80+. METHODS: Patients of ≥80 years diagnosed with rectal cancer between 2001 and 2010 were included. Population-based cohorts from Belgium (BE), Denmark (DK), the Netherlands (NL), Norway (NO) and Sweden (SE) were compared side by side for neighbouring countries on treatment strategy and 5-year relative survival (RS), adjusted for sex and age. Analyses were performed separately for stage I-III patients and stage IV patients. RESULTS: Overall, 19 634 rectal cancer patients were included. For stage I-III patients, 5-year RS varied from 61.7% in BE to 72.3% in SE. Proportion of preoperative radiotherapy ranged between 7.9% in NO and 28.9% in SE. For stage IV patients, 5-year RS differed from 2.8% in NL to 5.6% in BE. Rate of patients undergoing surgery varied from 22.2% in DK to 40.8% in NO. CONCLUSIONS: Substantial variation was observed in the 5-year relative survival between European countries for rectal cancer patients aged 80+, next to a wide variation in treatment, especially in the use of preoperative radiotherapy in stage I-III patients and in the rate of patients undergoing surgery in stage IV patients.

Variation in treatment and survival of older patients with non-metastatic breast cancer in five European countries: a population-based cohort study from the EURECCA Breast Cancer Group.

BACKGROUND: Older patients are poorly represented in breast cancer research and guidelines do not provide evidence based recommendations for this specific group. We compared treatment strategies and survival outcomes between European countries and assessed whether variance in treatment patterns may be associated with variation in survival. METHODS: Population-based study including patients aged ≥ 70 with non-metastatic BC from cancer registries from the Netherlands, Belgium, Ireland, England and Greater Poland. Proportions of local and systemic treatments, five-year relative survival and relative excess risks (RER) between countries were calculated. RESULTS: In total, 236,015 patients were included. The proportion of stage I BC receiving endocrine therapy ranged from 19.6% (Netherlands) to 84.6% (Belgium). The proportion of stage III BC receiving no breast surgery varied between 22.0% (Belgium) and 50.8% (Ireland). For stage I BC, relative survival was lower in England compared with Belgium (RER 2.96, 95%CI 1.30-6.72, P < .001). For stage III BC, England, Ireland and Greater Poland showed significantly worse relative survival compared with Belgium. CONCLUSIONS: There is substantial variation in treatment strategies and survival outcomes in elderly with BC in Europe. For early-stage BC, we observed large variation in endocrine therapy but no variation in relative survival, suggesting potential overtreatment. For advanced BC, we observed higher survival in countries with lower proportions of omission of surgery, suggesting potential undertreatment.

A classification prognostic score to predict OS in stage IV well-differentiated neuroendocrine tumors.

No validated prognostic tool is available for predicting overall survival (OS) of patients with well-differentiated neuroendocrine tumors (WDNETs). This study, conducted in three independent cohorts of patients from five different European countries, aimed to develop and validate a classification prognostic score for OS in patients with stage IV WDNETs. We retrospectively collected data on 1387 patients: (i) patients treated at the Istituto Nazionale Tumori (Milan, Italy; n = 515); (ii) European cohort of rare NET patients included in the European RARECAREnet database (n = 457); (iii) Italian multicentric cohort of pancreatic NET (pNETs) patients treated at 24 Italian institutions (n = 415). The score was developed using data from patients included in cohort (i) (training set); external validation was performed by applying the score to the data of the two independent cohorts (ii) and (iii) evaluating both calibration and discriminative ability (Harrell C statistic). We used data on age, primary tumor site, metastasis (synchronous vs metachronous), Ki-67, functional status and primary surgery to build the score, which was developed for classifying patients into three groups with differential 10-year OS: (I) favorable risk group: 10-year OS ≥70%; (II) intermediate risk group: 30% ≤ 10-year OS < 70%; (III) poor risk group: 10-year OS <30%. The Harrell C statistic was 0.661 in the training set, and 0.626 and 0.601 in the RARECAREnet and Italian multicentric validation sets, respectively. In conclusion, based on the analysis of three 'field-practice' cohorts collected in different settings, we defined and validated a prognostic score to classify patients into three groups with different long-term prognoses.

Treatment and Survival of Patients with Colon Cancer Aged 80 Years and Older: A EURECCA International Comparison.

BACKGROUND: Colon cancer in older patients represents a major public health issue. As older patients are hardly included in clinical trials, the optimal treatment of these patients remains unclear. The present international EURECCA comparison explores possible associations between treatment and survival outcomes in elderly colon cancer patients. SUBJECTS, MATERIALS, AND METHODS: National data from Belgium, Denmark, The Netherlands, Norway, and Sweden were obtained, as well as a multicenter surgery cohort from Germany. Patients aged 80 years and older, diagnosed with colon cancer between 2001 and 2010, were included. The study interval was divided into two periods: 2001-2006 and 2007-2010. The proportion of surgical treatment and chemotherapy within a country and its relation to relative survival were calculated for each time frame. RESULTS: Overall, 50,761 patients were included. At least 94% of patients with stage II and III colon cancer underwent surgical removal of the tumor. For stage II-IV, the proportion of chemotherapy after surgery was highest in Belgium and lowest in The Netherlands and Norway. For stage III, it varied from 24.8% in Belgium and 3.9% in Norway. For stage III, a better adjusted relative survival between 2007 and 2010 was observed in Sweden (adjusted relative excess risk [RER] 0.64, 95% confidence interval [CI]: 0.54-0.76) and Norway (adjusted RER 0.81, 95% CI: 0.69-0.96) compared with Belgium. CONCLUSION: There is substantial variation in the rate of treatment and survival between countries for patients with colon cancer aged 80 years or older. Despite higher prescription of adjuvant chemotherapy, poorer survival outcomes were observed in Belgium. No clear linear pattern between the proportion of chemotherapy and better adjusted relative survival was observed. IMPLICATIONS FOR PRACTICE: With the increasing growth of the older population, clinicians will be treating an increasing number of older patients diagnosed with colon cancer. No clear linear pattern between adjuvant chemotherapy and better adjusted relative survival was observed. Future studies should also include data on surgical quality.

Development and External Validation of Nomograms To Predict Adverse Pathological Characteristics After Robotic Prostatectomy: Results of a Prospective, Multi-institutional, Nationwide series.

BACKGROUND: The possibility of predicting pathologic features before surgery can support clinicians in selecting the best treatment strategy for their patients. We sought to develop and externally validate pretreatment nomograms for the prediction of pathological features from a prospective multicentre series of robotic-assisted laparoscopic prostatectomy (RALP) procedures. DESIGN, SETTING, AND PARTICIPANTS: Between 2009 and 2016, data from 6823 patients undergoing RALP in 25 academic and community hospitals were prospectively collected by the Belgian Cancer Registry. Logistic regression models were applied to predict extraprostatic extension (EPE; pT3a,b-4), seminal vesicle invasion (SVI; pT3b), and high-grade locally advanced disease (HGLA; pT3b-4 and Gleason score [GS] 8-10) using the following preoperative covariates: prostate-specific antigen, clinical T stage, biopsy GS, and percentage of positive biopsy cores. Internal and external validation was performed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The stability of the model was assessed via tenfold cross-validation using 80% of the cohort. The nomograms were independently externally validated using the test cohort. The discriminative accuracy of the nomograms was quantified as the area under the receiver operating characteristic curve and graphically represented using calibration plots. RESULTS AND LIMITATION: The nomograms predicting EPE, SVI, HGLA showed discriminative accuracy of 77%, 82%, and 88%, respectively. Following external validation, the accuracy remained stable. The prediction models showed excellent calibration properties. CONCLUSIONS: We developed and externally validated multi-institutional nomograms to predict pathologic features after RALP. These nomograms can be implemented in the clinical setting or patient selection in clinical trials. PATIENT SUMMARY: We developed novel nomograms using nationwide data to predict postoperative pathologic features and lethal prostate cancer.

Accuracy of pre-treatment locoregional rectal cancer staging in a national improvement project.

BACKGROUND: The aim of this study was to assess the accuracy, particularly the predictive value, of locoregional clinical rectal cancer staging (cTN) and its variability in a national improvement project. METHODS: cTN stages and the distance between tumour and mesorectal fascia (MRF) were compared with histopathological findings in 1168 patients who underwent radical resection without neoadjuvant treatment. Data were registered prospectively from 2006 to 2014. RESULTS: Agreement between clinical and histopathological TN stages was 50%, independent of tumour location. Inter-hospital variability was within 99% prediction limits. Magnetic resonance imaging (MRI) was increasingly applied, but staging accuracy did not improve. Stage II-III was correctly predicted in 69% and pStage I was over-staged in 35%. The positive predictive value of endorectal ultrasonography (ERUS) for T1 lesions was 57%. MRI-based distances to MRF correlated poorly with the circumferential resection margin (r = 0.26). A negative resection margin was achieved in 91% when the distance to the MRF was >1 mm. CONCLUSIONS: The accuracy of rectal cancer staging in general practice should be improved to avoid under- or overtreatment. Training and expert review of pre-treatment MR imaging could be helpful. A second ERUS is justified when transanal local resection for early lesions is planned.

Survival among clinical stage I-III rectal cancer patients treated with different preoperative treatments: A population-based comparison.

BACKGROUND: Radical resection is regarded as the cornerstone of rectal cancer treatment. Preoperative (chemo)radiotherapy and adjuvant chemotherapy are often administered. This population-based study compares the survival in clinical stage I-III rectal cancer patients who received either preoperative radiotherapy, preoperative chemoradiotherapy or no preoperative therapy. As secondary research questions, the association of type of radical resection and adjuvant chemotherapy on survival is also investigated. METHODS: Patients diagnosed between January 2006 and December 2011 with stage I-III rectal adenocarcinoma were retrieved from the Belgian Cancer Registry database. Multivariable Cox proportional hazards regression models were applied to evaluate the association of preoperative treatment, type of radical resection and use of adjuvant chemotherapy with survival, adjusting for the baseline characteristics age, gender, WHO performance status and clinical stage. RESULTS: A total of 5173 rectal cancer patients were identified. Preoperative treatment was as follows: none in 1354 (26.2%), radiotherapy in 797 (15.4%) and chemoradiotherapy in 3022 (58.4%) patients. The patient group who did not receive preoperative therapy or radiotherapy followed by radical resection had a lower observed survival compared to the patient group receiving preoperative chemoradiotherapy. The patient groups who underwent abdominoperineal excision and those receiving adjuvant chemotherapy had a worse observed survival compared to the patient group treated with sphincter-sparing surgery and no adjuvant therapy respectively. These effects were age-dependent. Multivariable analysis demonstrated similar findings for the observed survival conditional on surviving the first year since surgery. CONCLUSION: In this population-based study among clinical stage I-III rectal cancer patients treated with radical resection, a superior observed survival was noticed in the patient group receiving preoperative chemoradiotherapy compared to the patients groups receiving no or preoperative radiotherapy only, adjusting for case mix, type of radical resection and adjuvant chemotherapy. Additionally, higher adjusted observed survival was also detected for the patient groups with sphincter-sparing surgery or no adjuvant chemotherapy.

Regional variation in incidence for smoking and alcohol related cancers in Belgium.

The prevalence of life habits may vary substantially within a country. Incidence maps of strongly related diseases can illustrate the distribution of these life style habits. In this study we explored the spatial variation in Belgium for different cancers related to alcohol and/or tobacco. From the Belgian Cancer Registry, municipality specific World Standardised incidence rates for the years 2004-2011 are used to create detailed smoothed cancer maps by subsite or histology for cancers of oral cavity, pharynx, larynx, oesophagus, liver and lung. Cancer incidence is compared both visually (from incidence maps) and with Poisson regression analysis using mortality from chronic liver disease and chronic obstructive pulmonary disease as a proxy for alcohol and tobacco prevalence, respectively. The incidence rates for oral cavity, pharyngeal and laryngeal cancer were comparable with the alcohol gradient. However, glottic cancer revealed a pattern that was more comparable with lung cancer. These two tumour types resembled more closely to the smoking pattern. Oesophageal cancer showed two patterns: squamous cell carcinoma was highly comparable with the background alcohol consumption, while adenocarcinoma was unrelated to one of our two proxies. Our approach and results are an encouraging example how data from a young cancer registry can be used in studies describing the regional cancer burden. The results can be useful for primary prevention to increase awareness for the public, authorities and health care professionals in specific subpopulations.

Risk adjusted benchmarking of abdominoperineal excision for rectal adenocarcinoma in the context of the Belgian PROCARE improvement project.

OBJECTIVE: The abdominoperineal excision (APE) rate, a quality of care indicator in rectal cancer surgery, has been criticised if not adjusted for confounding factors. This study evaluates variability in APE rate between centres participating in PROCARE, a Belgian improvement initiative, before and after risk adjustment. It also explores the effect of merging the Hartmann resections (HR) rate with that of APE on benchmarking. DESIGN: Data of 3197 patients who underwent elective radical resection for invasive rectal adenocarcinoma up to 15 cm were registered between January 2006 and March 2011 by 59 centres, each with at least 10 patients in the registry. Variability of APE or merged APE/HR rates between centres was analysed before and after adjustment for gender, age, ASA score (3 or more), tumour level (rectal third), depth of tumour invasion (cT4) and preoperative incontinence. RESULTS: The overall APE rate was 21.1% (95% CI 19.7 to 22.5%). Significant variation of the APE rate was observed before and after risk adjustment (p<0.0001). For cancers in the lower rectal third, the overall APE rate increased to 45.8% (95% CI 43.1 to 48.5%). Also, variation between centres increased. Risk adjustment influenced the identification of outliers. HR was performed in only 2.6% of patients. However, merging of risk adjusted APE and HR rates identified other centres with outlying definitive colostomy rates than APE rate alone. CONCLUSION: Significant variation of the APE rate was observed. Adjustment for confounding factors as well as merging HR with APE rates were found to be important for the assessment of performances.