Long-term Overall Survival after External Beam Radiotherapy for Localised Prostate Cancer.

AIMS: Knowledge on survival probabilities is essential for determining optimal treatment strategies. We studied overall survival and associated prognostic factors in Dutch patients with localised prostate cancer (PCa) selected for external beam radiotherapy. MATERIALS AND METHODS: For this single-centre retrospective cohort study, we identified all T1-T3 PCa patients (aged 55-80 years) in the radiotherapy planning database with a start date between January 2006 and December 2013, treated with 72-78 Gy in 2 Gy fractions to the prostate ± seminal vesicles (n = 1536). Long-term androgen deprivation therapy (ADT) was predominantly prescribed in the case of extracapsular disease (>T3). Overall survival was estimated using the Kaplan-Meier method. Prognostic factors were evaluated in Cox regression models for the intermediate-risk and high-risk groups. RESULTS: The median follow-up was 12 years for patients who were alive. Ten-year survival rates were 79.0% for low-risk (n = 120), 59.9% for intermediate-risk (n = 430) and 56.8% for high-risk patients (n = 986). A higher age, higher comorbidity score, active smoking and Gleason score ≥8 had a statistically significant negative impact on overall survival at multivariable analysis. ADT was associated with superior overall survival in the high-risk group translating into overall survival rates similar to the intermediate-risk group. CONCLUSIONS: Although PCa patients selected for external beam radiotherapy are typically in good health, their comorbidity score and smoking habits appeared to be dominant predictors for overall survival. Overall survival rates within the high-risk group varied, showing improved overall survival with ADT prescription and worse overall survival in the case of Gleason score ≥8.

Variation in the management of cT1 renal cancer by surgical hospital volume: A nationwide study.

Objectives: To analyse variation in clinical management of cT1 renal cell carcinoma (RCC) in the Netherlands related to surgical hospital volume (HV). Materials and methods: Patients diagnosed with cT1 RCC during 2014-2020 were identified in the Netherlands Cancer Registry. Patient and tumour characteristics were retrieved. Hospitals performing kidney cancer surgery were categorised by annual HV as low (HV < 25), medium (HV = 25-49) and high (HV > 50). Trends over time in nephron-sparing strategies for cT1a and cT1b were evaluated. Patient, tumour and treatment characteristics of (partial) nephrectomies were compared by HV. Variation in applied treatment was studied by HV. Results: Between 2014 and 2020, 10 964 patients were diagnosed with cT1 RCC. Over time, a clear increase in nephron-sparing management was observed. The majority of cT1a underwent a partial nephrectomy (PN), although less PNs were applied over time (from 48% in 2014 to 41% in 2020). Active surveillance (AS) was increasingly applied (from 18% to 32%). For cT1a, 85% received nephron-sparing management in all HV categories, either with AS, PN or focal therapy (FT). For T1b, radical nephrectomy (RN) remained the most common treatment (from 57% to 50%). Patients in high-volume hospitals underwent more often PN (35%) for T1b compared with medium HV (28%) and low HV (19%). Conclusion: HV is related to variation in the management of cT1 RCC in the Netherlands. The EAU guidelines have recommended PN as preferred treatment for cT1 RCC. In most patients with cT1a, nephron-sparing management was applied in all HV categories, although differences in applied strategy were found and PN was more frequently used in high HV. For T1b, high HV was associated with less appliance of RN, whereas PN was increasingly used. Therefore, closer guideline adherence was found in high-volume hospitals.

Impact of Advanced External Beam Radiotherapy on Second Haematological Cancer Risk in Prostate Cancer Survivors.

AIMS: External beam radiotherapy (EBRT) for prostate cancer (PCa) has rapidly advanced over the years. Advanced techniques with altered dose distributions may have an impact on second haematological cancer (SHC) risks. We assessed SHC risk after EBRT for PCa and explored whether this risk has changed over the years. MATERIALS AND METHODS: Patients diagnosed with a T1-T3 PCa between 1990 and 2015 were selected from the Netherlands Cancer Registry. Patients treated with EBRT were assigned to EBRT eras based on the date of diagnosis. These eras represented two-dimensional radiotherapy (2D-RT; 1991-1996), three-dimensional conformal radiotherapy (3D-CRT; 1998-2005) or advanced EBRT (2008-2015). Standardised incidence ratios (SIR) and absolute excess risks (AER) were calculated overall and by EBRT era. Sub-hazard ratios (sHRs) were calculated for the comparison of EBRT versus radical prostatectomy and active surveillance. RESULTS: PCa patients with EBRT as the primary treatment (n = 37 762) had an increased risk of developing a SHC (SIR = 1.20; 95% confidence interval 1.13-1.28) compared with the Dutch male general population. Estimated risks were highest for the 2D-RT era (SIR = 1.32; 95% confidence interval 1.14-1.67) compared with the 3D-CRT era (SIR = 1.16; 95% confidence interval 1.05-1.27) and the advanced EBRT era (SIR = 1.21; 95% confidence interval 1.07-1.36). AER were limited, with about five to six extra cases per 10 000 person-years. Relative risk analysis (EBRT versus radical prostatectomy/active surveillance) showed significant elevation with EBRT versus active surveillance (sHR = 1.17; 95% confidence interval 1.03-1.33; P = 0.017), but not for EBRT versus radical prostatectomy (sHR = 1.08; 95% confidence interval 0.94-1.23; P = 0.281). CONCLUSION: Increased SHC risks after EBRT for PCa cancer were observed for all EBRT eras compared with the general Dutch male population. Excess risks for EBRT versus other PCa treatment groups were found for only EBRT versus active surveillance.

Role of multidisciplinary team meetings in implementation of chemohormonal therapy in metastatic prostate cancer in daily practice.

BACKGROUND: The recommended treatment for a subset of patients with metastatic prostate cancer (mPC) changed from androgen deprivation therapy (ADT) to combinations with chemotherapy such as docetaxel. Implementation of new evidence from trials is however complex and challenging. We investigated the effect of multidisciplinary team meetings (MDTs) on adopting the newest emerging combination therapy in patients with mPC and assessed the overall survival of chemohormonal therapy in a real-world setting. METHODS: All mPC patients diagnosed between October 2015 and April 2016 in the Netherlands were identified from the population-based Netherlands Cancer Registry (n = 962). Logistic regression analyses were performed to examine the role of patient- and tumor characteristics, with special emphasis on MDTs, on receiving chemohormonal therapy versus ADT monotherapy. Kaplan-Meier survival curves were used to assess overall survival (OS). RESULTS: As many patients received ADT monotherapy as chemohormonal therapy (both n = 452). Being discussed in a MDT as patient, younger age, less comorbidities, a better performance status and high-volume disease were significantly associated with receiving chemohormonal therapy compared to ADT monotherapy. After adjustment for these factors, the presence of a MDT was independently associated with the administration of chemohormonal therapy (OR 2.77, 95% CI 1.68-4.59). The 2-year OS was 82.1% (95% CI: 78.5-85.6%) for patients receiving chemohormonal therapy and 59.9% (95% CI: 55.4-64.4%) for patients receiving ADT monotherapy. CONCLUSION: Being discussed in a MDT is independently associated with the administration of chemohormonal therapy in this group of patients with mPC. This supports the hypothesis that implementation of innovative treatment options is facilitated by an organizational structure with MDTs.

Validation and reliability of the Dutch version of the EORTC QLQ-BLM30 module for assessing the health-related quality of life of patients with muscle invasive bladder cancer.

BACKGROUND: Quality of Life (QoL) of bladder cancer patients has been largely neglected. This is partly due to the lack of well-validated QoL questionnaires. The aim of this study is to examine the structural validity, reliability (i.e., internal consistency and test-retest reliability), construct validity (i.e., divergent validity and known group validity) and responsiveness of the Dutch version of the European Organisation for Research and Treatment of Cancer QoL questionnaire for muscle invasive bladder cancer (EORTC-QLQ-BLM30). METHODS: Patients with newly diagnosed muscle invasive bladder cancer (MIBC) participating in the population-based 'Blaaskankerzorg In Beeld' (BlaZIB) study who completed the EORTC-QLQ-BLM30 at baseline were included. BlaZIB is a Dutch nationwide population-based prospective cohort study collecting clinical data and QoL data of bladder cancer patients. QoL is assessed with a self-administered questionnaire at four points in time: 6 weeks (baseline), 6 months, 12 months and 24 months after diagnosis. Confirmatory factor analysis and multitrait scaling analysis were used to investigate and adapt the scale structure. Reliability, construct validity and responsiveness of the revised scales were evaluated. RESULTS: Of the 1542 patients invited to participate, 650 patients (42.2%) completed the QLQ-BLM30 at baseline. The questionnaire's scale structure was revised into seven scales and eight single items. Internal consistency and test-reliability were adequate for most scales (Cronbach's α ≥0.70 and intraclass correlation coefficient ≥ 0.70, respectively), with the exception of the revised urostomy problem scale and abdominal bloating and flatulence scale. The questionnaire exhibited little overlap with the EORTC-QLQ-C30: all correlations were < 0.40, except for the correlation between emotional function (QLQ-C30) and future worries (QLQ-BLM30). The questionnaire was able to distinguish between patient subgroups formed on the basis of physical function, but not - as hypothesized- based on stage. Changes in health due to treatment were captured by the questionnaire, indicating that the questionnaire is responsive to change. CONCLUSIONS: This study shows that the adapted scale structure of the EORTC-QLQ-BLM30 generally exhibits good measurement properties in Dutch patients, but needs to be validated in other languages and settings. TRIAL REGISTRATION: BlaZIB, NL8106, www.trialregister.nl.

Association of visceral and subcutaneous adiposity with tumor stage and Fuhrman grade in renal cell carcinoma.

Higher BMI has been associated with lower tumor stage and grade and improved survival in renal cell cancer (RCC). BMI cannot distinguish between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). We examined associations of BMI, VAT, SAT, total adipose tissue (TAT) and relative VAT (rVAT) with tumor stage and grade in RCC patients. In a Dutch multicenter population-based historical cohort study 1039 RCC patients diagnosed between 2008 and 2012 were assessed for VAT and SAT using Computed Tomography images at L3. Sex-stratified multinomial logistic regression analyses were performed (linearly per 10-unit increase) between BMI, VAT, SAT, TAT and relative VAT (rVAT) with tumor stage and Fuhrman grade. Higher VAT, TAT and rVAT were associated with a lower risk of stage IV versus stage I in males (OR 0.93; 95%CI 0.91-0.96, OR 0.95; 95%CI 0.93-0.98, OR 0.97; 95%CI 0.96-0.99, respectively). Females showed similar associations, but only higher VAT was statistically significantly associated with reduced risk of stage IV (OR 0.95 95%CI 0.89-1.00). No associations with grade, SAT or BMI were found. In conclusion, higher VAT and TAT was associated with lower risk of stage IV RCC. This might be due to weight loss or cancer cachexia in stage IV patients.

Occult lymph node metastases in patients without residual muscle-invasive bladder cancer at radical cystectomy with or without neoadjuvant chemotherapy: a nationwide study of 5417 patients.

PURPOSE: Little is known about the prevalence of occult lymph node metastases (LNM) in muscle-invasive bladder cancer (MIBC) patients with pathological downstaging of the primary tumor. We aimed to estimate the prevalence of occult LNM in patients without residual MIBC at radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC) or neoadjuvant radiotherapy (NAR), and to assess overall survival (OS). METHODS: Patients with cT2-T4aN0M0 urothelial MIBC who underwent RC plus pelvic lymph node dissection (PLND) with curative intent between January 1995-December 2013 (retrospective Netherlands Cancer Registry (NCR) cohort) and November 2017-October 2019 (prospective NCR-BlaZIB cohort (acronym in Dutch: BlaaskankerZorg In Beeld; in English: Insight into bladder cancer care)) were identified from the nationwide NCR. The prevalence of occult LNM was calculated and OS of patients with <(y)pT2N0 vs. <(y)pT2N+ disease was estimated by the Kaplan-Meier method. RESULTS: In total, 4657 patients from the NCR cohort and 760 patients from the NCR-BlaZIB cohort were included. Of 1374 patients downstaged to <(y)pT2, 4.3% (N = 59) had occult LNM 4.1% (N = 49) of patients with cT2-disease and 5.6% (N = 10) with cT3-4a-disease. This was 4.0% (N = 44) in patients without NAC or NAR, 4.5% (N = 10) in patients with NAC, and 13.5% (N = 5) in patients with NAR but number of patients treated with NAR and downstaged disease was small. The prevalence of <(y)pT2N+ disease was 4.2% (N = 48) in the NCR cohort and 4.6% (N = 11) in the NCR-BlaZIB cohort. For patients with <(y)pT2N+ and <(y)pT2N0, median OS was 3.5 years (95% CI 2.5-8.9) versus 12.9 years (95% CI 11.7-14.0), respectively. CONCLUSION: Occult LNM were found in 4.3% of patients with cT2-4aN0M0 MIBC with (near-) complete downstaging of the primary tumor following RC plus PLND. This was regardless of NAC or clinical T-stage. Patients with occult LNM showed considerable worse survival. These results can help in counseling patients for bladder-sparing treatments.

The effects of new life-prolonging drugs for metastatic castration-resistant prostate cancer (mCRPC) patients in a real-world population.

BACKGROUND: In 2004 docetaxel was the first life-prolonging drug (LPD) registered for metastatic castration-resistant prostate cancer (mCRPC) patients. Between 2011 and 2014 new LPDs for mCRPC (cabazitaxel, abiraterone, enzalutamide, and radium-223) were introduced in the Netherlands. The objective of this study is to assess the impact of the introduction of new LPDs on treatment patterns and overall survival (OS) over time. PATIENTS AND METHODS: CRPC patients diagnosed in the years 2010-2016 in the observational, retrospective CAPRI registry (20 hospitals) were included and followed up to 2018. Two subgroups were analyzed: treatment-naïve patients (subgroup 1, n = 3600) and post-docetaxel patients (subgroup 2, n = 1355). RESULTS: In both subgroups, the use of any LPD increased: from 57% (2010-2011) to 69% (2014-2015) in subgroup 1 and from 65% (2011-2012) to 79% (2015-2016) in subgroup 2. Chemotherapy as first mCRPC-treatment (i.e., docetaxel) and first post-docetaxel treatment (i.e., cabazitaxel or docetaxel rechallenge) decreased (46-29% and 20-9% in subgroup 1 and 2, respectively), while the use of androgen-receptor targeting treatments (ART) increased from 11% to 39% and 46% to 64% in subgroup 1 and 2, respectively. In subgroup 1, median OS (mOS) from diagnosis CRPC increased from 28.5 months to 31.0 months (p = 0.196). In subgroup 2, mOS from progression on docetaxel increased from 7.9 months to 12.5 months (p < 0.001). After multiple imputations of missing values, in multivariable cox-regression analysis with known prognostic parameters, the treatment period was independent significant for OS in subgroup 1 (2014-2015 vs. 2010-2011 with HR 0.749, p < 0.001) and subgroup 2 (2015-2016 vs. 2011-2012 with HR 0.811, p = 0.037). CONCLUSION: Since 2010, a larger proportion of mCRPC patients was treated with LPDs, which was related to an increased mOS.

Histopathological re-evaluations of biopsies in prostate cancer: a nationwide observational study.

BACKGROUND: Grading prostate biopsies has an important role in determining treatment strategy. Histopathological evaluations suffer from interobserver variability and therefore biopsies may be re-evaluated. OBJECTIVE: To provide insight into the extent of, characteristics associated with and clinical implications of prostate biopsy re-evaluations in daily clinical practice. METHODS: Patients diagnosed with prostate cancer (PCa) by biopsy between October 2015 and April 2016 identified through the Netherlands Cancer Registry were included. The proportion of re-evaluations was assessed and characteristics were compared between patients with and without biopsy re-evaluation. Interobserver concordance of ISUP grade and EAU prognostic risk classification was determined by calculating Cohen's kappa. RESULTS: Biopsy re-evaluation was performed in 172 (3.3%) of 5214 patients. Primary reason for re-evaluation in patients treated with curative intent was referral to another hospital. Most referred patients treated with curative intent (n = 1856) had no re-evaluation (93.0%, n = 1727). Patients with biopsy re-evaluation were younger and underwent more often prostatectomy compared to patients without re-evaluation. The disagreement rate for ISUP grade was 26.1% and interobserver concordance was substantial (κ-weighted = 0.74). Re-evaluation resulted in 21.1% (n = 14) of patients with localised PCa in a different prognostic risk group. More tumours were downgraded (57.1%) than upgraded (42.9%). Interobserver concordance was very good (κ weighted = 0.85). CONCLUSION: Pathology review of prostate biopsies is infrequently requested by clinicians in the Netherlands but in a non-negligible minority of patients with localised PCa the pathology review led to a change in prognostic risk group which might impact their treatment.

Urinary incontinence and erectile dysfunction in patients with localized or locally advanced prostate cancer: A nationwide observational study.

BACKGROUND: Although urinary adverse events after treatment of prostate cancer (CaP) are common, population-based studies on functional outcomes are scarce. The aim of this study is to evaluate the occurrence of urinary incontinence (UI) and erectile dysfunction (ED) in daily clinical practice using a nationwide Dutch cohort of patients with localized or locally advanced CaP. BASIC PROCEDURES: Patients were invited to complete the EPIC-26 questionnaire before treatment (baseline) and at 12 and 24 months after diagnosis. We calculated the mean EPIC-26 domain scores, stratified by treatment modality (i.e., radical prostatectomy, external radiotherapy, and no active treatment), and the proportions of patients with UI (defined as ≥ 2 pads per day) and ED (defined as erections not firm enough for sexual intercourse). Logistic regression modeling was used to explore the factors related to UI and ED after surgery. MAIN FINDINGS: In total 1,759 patients participated in this study. Patients undergoing radical prostatectomy experienced clinically relevant worsening in the urinary incontinence domain. After excluding patients who reported UI at baseline, 15% of patients with prostatectomy reported UI 24 months after diagnosis. Only comorbidity was associated with UI in surgically treated patients. Regardless of treatment, patients reported a clinically significant reduced sexual functioning over time. Before treatment, 54% of patients reported ED. Among the 46% remaining patients, 87% of patients treated with radical prostatectomy reported ED 24 months after diagnosis, 41% after radiotherapy, and 46% in patients without active treatment. Bilateral nerve-sparing surgery was the only factor associated with ED after 24 months. PRINCIPAL CONCLUSIONS: UI and ED frequently occur in patients with localized and locally advanced CaP, in particular after radical prostatectomy. The higher occurrence rate of UI and ED, compared with clinical trial participants, supports the importance of real-world data, which can be used for local treatment recommendations and patient information, but also to evaluate effects of future initiatives, such as treatment centralization and research aimed at improving functional outcomes.

Insight into bladder cancer care: study protocol of a large nationwide prospective cohort study (BlaZIB).

BACKGROUND: Despite the embedding of bladder cancer management in European guidelines, large variation in clinical practice exists for applied diagnostics and treatments. This variation may affect patients' outcomes including complications, disease recurrence, progression, survival, and health-related quality of life (HRQL). Lack of detailed clinical data and HRQL data hampers a comprehensive evaluation of bladder cancer care. Through prospective data registration, this study aims to provide insight in bladder cancer care in the Netherlands and to identify barriers and modulators of optimal bladder cancer care. METHODS: This study is a nationwide prospective cohort study including all patients who were newly diagnosed with high-risk non-muscle invasive bladder cancer (HR-NMIBC; Tis and/or T1, N0, M0/x) or non-metastatic muscle invasive bladder cancer (MIBC; ≥T2, N0/x-3, M0/x) in the Netherlands between November 1st 2017 and October 31st 2019. Extensive data on patient- and tumor characteristics, diagnostics, treatment and follow-up up to 2 years after diagnosis will be collected prospectively from electronic health records in the participating hospitals by data managers of the Netherlands Cancer Registry (NCR). Additionally, patients will be requested to participate in a HRQL survey shortly after diagnosis and subsequently at 6, 12 and 24 months. The HRQL survey includes six standardized questionnaires, e.g. SCQ Comorbidity score, EQ-5D-5 L, EORTC-QLQ-C30, EORTC-QLQ-BLM30, EORTC-QLQ-NMIBC24 and BCI. Variation in care and deviation from the European guidelines will be assessed through descriptive analyses and multivariable multilevel analyses. Survival analyses will be used to assess the association between variation in care and relevant outcomes such as survival. DISCUSSION: The results of this observational study will guide modifications of clinical practice and/or adaptation of guidelines and may set the agenda for new specific research questions in the management of bladder cancer. TRIAL REGISTRATION: Retrospectively registered in the Netherlands Trial Register. Trial identification number: NL8106. Registered on October 22nd 2019.

Analysis of 105.000 patients with cancer: have they been discussed in oncologic multidisciplinary team meetings? A nationwide population-based study in the Netherlands.

INTRODUCTION: For optimal oncological care, it is recommended to discuss every patient with cancer in a multidisciplinary team meeting (MDTM). This is a time consuming and expensive practice, leading to a growing demand to change the current workflow. We aimed to investigate the number of patients discussed in MDTMs and to identify characteristics associated with not being discussed. METHODS: Data of patients with a newly diagnosed solid malignant tumour in 2015 and 2016 were analysed through the nationwide population-based Netherlands Cancer Registry (NCR). We clustered tumour types in groups that were frequently discussed within a tumour-specific MDTM. Tumour types without information about MDTMs in the NCR were excluded. Multivariable logistic regression analyses were used to analyse factors associated with not being discussed. RESULTS: Out of 105.305 patients with cancer, 91% were discussed in a MDTM, varying from 74% to 99% between the different tumour groups. Significantly less frequently discussed were patients aged ≥75 years (odds ratio [OR] = 0.7, 95% confidence interval [CI] = 0.6-0.7), patients diagnosed with disease stage I (OR = 0.5, 95% CI = 0.5-0.6), IV (OR = 0.4, 95% CI = 0.4-0.4) or unknown (OR = 0.2, 95% CI = 0.2-0.2) and patients who received no treatment (OR = 0.3, 95% CI = 0.3-0.3). Patients who received a multidisciplinary treatment were more likely to be discussed in contrary to a monodisciplinary treatment (OR = 4.6, 95% CI = 4.2-5.1). CONCLUSION: In general, most patients with cancer were actually discussed in a MDTM, although differences were observed between tumour groups. Factors associated with not being discussed may, at least partially, reflect the absence of a multidisciplinary question. These results form a starting point for debate on a more durable and efficient new MDTM strategy.

Bladder cancer survival: Women only fare worse in the first two years after diagnosis.

OBJECTIVES: It has consistently been shown that women who are diagnosed with bladder cancer have lower survival than men, but the exact mechanism remains unknown. Most studies assumed that the sex-specific mortality ratio is constant over time, possibly resulting in inaccurate estimates in various periods of follow-up. This study aimed to investigate the sex-specific excess mortality in bladder cancer patients and its variation over follow-up time. METHODS: Observational cohort study. Using data from the population-based Netherlands Cancer Registry, we studied 24,169 patients diagnosed between 2003 and 2014 with histologically confirmed ≥T1 bladder cancer with follow-up until January 2018. We used flexible parametric relative survival models to estimate excess mortality as a function of time for each sex and to explore the effect of covariates on these functions. RESULTS: Female patients (24%) had worse clinical tumor, node, and metastasis-stage at diagnosis and more often a nonurothelial tumor histology. The excess mortality ratio of sex was not constant over time; in the first two years after diagnosis excess mortality rates for women were higher than for men, but lower thereafter; this applied to both nonmuscle-invasive and muscle-invasive bladder cancer subgroups. Baseline differences in age, tumor, node, and metastasis-stage and histology accounted for only part of the excess mortality gap. CONCLUSIONS: The assumption of proportional hazards over time leads to underestimation of the excess mortality ratio for women in the first two years and overestimation thereafter, when excess mortality is comparable for women and men. Clinicians should incorporate the initial sex-specific poorer outcome in their considerations regarding prognosis and treatment options for female patients, e.g., more invasive treatment and neo-adjuvant treatment. These findings also point towards a mechanism of micrometastatic disease, warranting assessment of sex-specific efficacy in randomized controlled trials on treatments in this patient population.

[Incidence of incontinence after radical prostatectomy using claims-based data]. / Hoe vaak incontinentie na radicale prostatectomie?

OBJECTIVE: To determine the effect of radical prostatectomy (RP) hospital volume on the probability of post-RP incontinence. DESIGN: Retrospective research based on claims-based data of health insurers. METHOD: For every patient with RP the probability of incontinence was determined, based on the definition of claims of one or more incontinence pads per day. Casemix corrections were made based on indicators available in claims-data: age, lymph node dissection, and radiotherapy. No casemix corrections could be made for tumour stage and surgical technique. RESULTS: A total of 1590 patients were included in this study; for 26.0% of these patients, an average of one or more incontinence pads per day were claimed for. A significant relation between the volume of RP per hospital and the claims of incontinence material was observed. The probability of incontinence was significantly lower in hospitals with a volume of more than 100 RP patients per year when compared to hospitals with less than 100 RP patients per year. CONCLUSION: The probability of post-RP incontinence decreases as hospitals conduct more RP procedures. The casemix factors included in the analysis only had a limited impact on this observation.

Reduce bladder cancer recurrence in patients treated for upper urinary tract urothelial carcinoma: The REBACARE-trial.

BACKGROUND: Following radical nephro-ureterectomy for urothelial carcinoma of the upper urinary tract (UUT), the reported bladder recurrence rate of urothelial carcinoma is 22-47%. A single intravesical instillation of chemotherapy within 10 days following nephro-ureterectomy has the potential to decrease the risk of a bladder recurrence significantly. Despite recommendation by the European Association of Urology guideline to administer a single instillation postoperatively, the compliance rate is low because the risk of extravasation of chemotherapy. AIM: To reduce the risk of bladder cancer recurrence by a single intravesical instillation of Mitomycin immediately (within 3 h) before radical nephro-ureterectomy or partial ureterectomy. METHODS: Adult patients (age ≥ 18 years) with a (suspicion of a) urothelial carcinoma of the UUT undergoing radical nephro-ureterectomy or partial ureterectomy will be eligible and will receive a single intravesical instillation of Mitomycin within 3 h before surgery. In total, 170 patients will be included in this prospective, observational study. Follow-up will be according to current guidelines. RESULTS: The primary endpoint is the bladder cancer recurrence rate up to two years after surgery. Secondary endpoints are: a) the compliance rate; b) oncological outcome; c) possible side-effects; d) the quality of life; e) the calculation of costs of a single neoadjuvant instillation with Mitomycin and f) molecular characterization of UUT tumors and intravesical recurrences. CONCLUSIONS: A single intravesical instillation of Mitomycin before radical nephro-ureterectomy or partial ureterectomy may reduce the risk of a bladder recurrence in patients treated for UUT urothelial carcinoma and will circumvent the disadvantages of current therapy.

Risk factors for second primary melanoma among Dutch patients with melanoma.

BACKGROUND: Patients with melanoma are at increased risk of developing subsequent primary melanomas. Knowledge about risk factors for these subsequent primaries is scarce. More evidence may help clinicians in tailoring surveillance schedules by selecting patients who could benefit from intensified surveillance. OBJECTIVES: To identify risk factors for a second primary cutaneous melanoma. METHODS: Possible risk factors for a second primary melanoma were assessed in 1127 patients with cutaneous melanoma who were diagnosed between 2003 and 2011 and completed a baseline questionnaire. Additional data were extracted from the Netherlands Cancer Registry and medical files. RESULTS: Fifty-three patients were diagnosed with a second melanoma during a median follow-up time of 6·3 years. The 5-year cumulative risk was 3·7% and the conditional cumulative risk was 4·6% in years 5-10 after diagnosis. In multivariable analyses, the risk of a second melanoma increased with older age at diagnosis [hazard ratio (HR) 1·03 per year; 95% confidence interval (CI) 1·00-1·06], a high naevus density (HR 7·16, 95% CI 2·89-17·75) and working outside for > 10 years (HR 2·88, 95% CI 1·38-6·03). Patients with invasive melanoma (> 1 mm) had a decreased risk compared with patients with melanoma in situ (HR 0·35, 95% CI 0·13-0·93). CONCLUSIONS: Besides phenotypic characteristics, cumulative sun exposure seemed to increase the risk of a second melanoma. Patients with melanoma in situ may need to be offered follow-up, which is currently not advised. As the risk of a second melanoma did not decline in years 5-10 after diagnosis, a subgroup of patients may need a longer follow-up than is currently advised.

Limited role for histopathological examination of re-excision specimens of completely excised melanomas.

The Dutch melanoma guideline advises to examine one central block of the re-excision scar in case of a complete primary excision. To increase the evidence for this recommendation, we re-evaluated how often residual melanoma was found in re-excision specimens of a large series of completely excised melanomas. Of 1,209 Dutch melanoma cases, pathology reports of primary excisions were reviewed. Presence of melanoma in the margins was scored. All melanomas with a complete primary excision were included and pathology reports of re-excisions were reviewed. Presence of residual melanoma in the re-excision specimen and the number of blocks were scored. Slides of re-excision specimens containing residual melanoma were reviewed. Eventually, in four out of 812 melanomas (0.5 %) with a complete primary excision, residual melanoma was found in the re-excision specimen. The free margins of the primary melanomas in these cases ranged from 0.5-3.5 mm. In one case, the margin for melanoma in situ was 0.2 mm. In <1 % of initially completely excised melanomas, residual melanoma was found in the re-excision specimen. Histopathological examination of these re-excision specimens may not be cost-efficient. Our findings even imply that a re-excision could safely be omitted in selected cases of completely excised melanomas.

Impact of mitotic activity on the pathological substaging of pT1 cutaneous melanoma.

BACKGROUND: In the transition from the sixth to the seventh edition of the American Joint Committee on Cancer (AJCC) melanoma staging system, mitotic activity was incorporated, while Clark level of invasion was abandoned. OBJECTIVES: To investigate the effect of this change on the pathological tumour (pT)1 substaging of primary cutaneous melanomas and the possible clinical implications. METHODS: Patients with pT1 melanomas, diagnosed in the period January 2003 to March 2011, were selected from a population-based cohort study on cutaneous melanoma in the eastern part of the Netherlands. The pT1 melanomas were systematically reviewed by an expert pathologist and classified according to both the sixth and the seventh editions of the AJCC staging system. The shift of melanomas between pT1 substages, classified according to the two staging systems, was determined. RESULTS: In total, 260 pT1 melanomas were included. Overall 28% (57/207) of all pT1a melanomas shifted to pT1b when classified according to the new seventh staging classification, because of the presence of mitoses. Some 32% (17/53) of all pT1b melanomas shifted to pT1a. The percentage of pT1b melanomas relative to all pT1 melanomas increased from 20% to 36%. CONCLUSIONS: The addition of mitotic activity to the pathological staging system, according to the seventh edition of the AJCC staging system, resulted in a considerable change in the classification of thin cutaneous melanomas. This shift has clear clinical implications, as it is advised in the Dutch guideline that patients with pT1b melanoma should be offered a sentinel lymph node biopsy.

New insights into the aetiology of scrotal cancer, a nationwide case-control study in the Netherlands.

BACKGROUND: Although scrotal cancer is traditionally regarded as an occupational disease, there is increasing evidence that factors which are involved in cutaneous and genital carcinogenesis might play a role in the carcinogenesis of scrotal cancer. OBJECTIVE: This exploratory study aimed to detect exposures that might have an aetiological relation with scrotal cancer. METHODS: A nationwide population-based case-control study was conducted in the Netherlands. The patients were identified through the Netherlands cancer registry. Controls were recruited among acquaintances of the cancer registry registrars. The participants completed a questionnaire that included questions on occupational exposures, naked sunbathing, use of sunbeds, skin diseases and their treatments, treatments for cancer and sexually transmitted diseases. Age-adjusted odds-ratios (ORs) were calculated. RESULTS: Forty-seven scrotal cancer patients and 125 controls completed the questionnaire. The patients were categorized according to histology of the scrotal tumours. Having had a skin disease (OR = 6.3, 95% CI = 1.8-22), especially psoriasis (OR = 8.7), increased the risk of squamous cell carcinomas (SCC) of the scrotum. A previous cancer diagnosis may affect the risk of scrotal basal cell carcinomas (BCC; OR = 4.9, 95% CI = 0.9-27.3). Furthermore, an association between the number of sexual partners and the occurrence of scrotal sarcoma was found. CONCLUSION: Scrotal SCCs may be related with skin diseases or skin disease treatments. Having had cancer may be a risk factor for a BCC of the scrotum. Scrotal sarcomas seem to be correlated with the number of sexual partners. This study suggests that scrotal cancer has characteristics of both cutaneous and genital carcinogenesis.