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.

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.

[The relationship between lifestyle and cancer; topic of conversation in the consultation room?] / Relatie tussen leefstijl en kanker.

OBJECTIVE: This survey explores the degree of consensus amongst healthcare professionals for the support of cancer patients' lifestyle management, based on three questions posed to them: a) what do they know about the relation between lifestyle and cancer?; b) do they consider lifestyle support for cancer patients part of their professional role?; c) does their own lifestyle influence the lifestyle management consultations they may have with cancer patients? Design Survey study. METHOD: A digital questionnaire with questions concerning lifestyle and cancer was sent to 1550 healthcare professionals in and around Nijmegen. The questionnaire was filled out by 562 healthcare professionals (36% response rate), of whom 404 (72%) were involved in cancer patient care. This cohort of responders consisted of 170 medical specialists, 62 general practitioners, and 172 nurses and allied health professionals. RESULTS: Healthcare professionals acknowledge the influence of lifestyle on the development of cancer. Almost all healthcare professionals (98%) agree on the positive effects of a healthy lifestyle on the well-being of cancer patients. Approximately two-thirds of all responders believe that lifestyle support should 'usually' or 'always' form part of cancer care; about fifty percent report to implement this in clinical practice. Healthcare professionals require evidence-based knowledge concerning the relationship between lifestyle and cancer, patient information materials, and additional consultation time to support lifestyle management involving cancer patients. The healthcare professionals' own lifestyle appears to have an influence: in those responders who do not adhere to a healthy lifestyle themselves, lifestyle was also covered less in consultations. CONCLUSION: This explorative survey shows that lifestyle support of cancer patients is deemed an important topic amongst healthcare professionals.

Health-related quality of life and its determinants in patients with metastatic renal cell carcinoma.

PURPOSE: Based on improvements of progression-free survival (PFS), new agents for metastatic renal cell carcinoma (mRCC) have been approved. It is assumed that one of the benefits is a delay in health-related quality of life (HRQoL) deterioration as a result of a delay in progression of disease. However, little data are available supporting this relationship. This study aims to provide insight into the most important determinants of HRQoL (including progression of disease) of patients with mRCC. METHODS: A patient registry (PERCEPTION) was created to evaluate treatment of patients with (m)RCC in the Netherlands. HRQoL was measured, using the EORTC QLQ-C30 and EQ-5D-5L, every 3 months in the first year of participation in the study, and every 6 months in the second year. Participation started as soon as possible following a diagnosis of (m)RCC. Random effects models were used to study associations between HRQoL and patient and disease characteristics, symptoms and treatment. RESULTS: Eighty-seven patients with mRCC completed 304 questionnaires. The average EORTC QLQ-C30 global health status was 69 (SD, 19) before progression and 61 (SD, 22) after progression of disease. Similarly, the average EQ-5D utility was 0.75 (SD, 0.19) before progression and 0.66 (SD, 0.30) after progression of disease. The presence of fatigue, pain, dyspnoea, and the application of radiotherapy were associated with significantly lower EQ-5D utilities. CONCLUSIONS: Key drivers for reduced HRQoL in mRCC are disease symptoms. Since symptoms increase with progression of disease, targeted therapies that increase PFS are expected to postpone reductions in HRQoL in mRCC.

Potential health gains for patients with metastatic renal cell carcinoma in daily clinical practice: A real-world cost-effectiveness analysis of sequential first- and second-line treatments.

INTRODUCTION: Randomised controlled trials have shown that targeted therapies like sunitinib are effective in metastatic renal cell carcinoma (mRCC). Little is known about the current use of these therapies, and their associated costs and effects in daily clinical practice. We estimated the real-world cost-effectiveness of different treatment strategies comprising one or more sequentially administered drugs. METHODS: Analyses were performed using patient-level data from a Dutch population-based registry including patients diagnosed with primary mRCC from January 2008 to December 2010 (i.e., treated between 2008 and 2013). The full disease course of these patients was estimated using a patient-level simulation model based on regression analyses of the registry data. A healthcare sector perspective was adopted; total costs included healthcare costs related to mRCC. Cost-effectiveness was expressed in cost per life-year and cost per quality-adjusted life-year (QALY) gained. Probabilistic sensitivity analysis was conducted to estimate the overall uncertainty surrounding cost-effectiveness. RESULTS: In current daily practice, 54% (336/621) of all patients was treated with targeted therapies. Most patients (84%; 282/336) received sunitinib as first-line therapy. Of the patients receiving first-line therapy, 30% (101/336) also received second-line therapy; the majority was treated with everolimus (40%, 40/101) or sorafenib (28%, 28/101). Current treatment practice (including patients not receiving targeted therapy) led to 0.807 QALYs; mean costs were €58,912. This resulted in an additional €105,011 per QALY gained compared to not using targeted therapy at all. Forty-six percent of all patients received no targeted therapy; of these patients, 24% (69/285) was eligible for sunitinib. If these patients were treated with first-line sunitinib, mean QALYs would improve by 0.062-0.076 (where the range reflects the choice of second-line therapy). This improvement is completely driven by the health gain seen amongst patients eligible to receive sunitinib but did not receive it, who gain 0.558-0.684 QALYs from sunitinib. Since additional costs would be €7,072-9,913, incremental costs per QALY gained are €93,107-111,972 compared to current practice. DISCUSSION: Health can be gained if more treatment-eligible patients receive targeted therapies. Moreover, it will be just as cost-effective to treat these patients with sunitinib as current treatment practice.

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.

Variation in use of targeted therapies for metastatic renal cell carcinoma: Results from a Dutch population-based registry.

BACKGROUND: For patients with metastatic renal cell carcinoma (mRCC), targeted therapies have entered the market since 2006. The aims of this study were to evaluate the uptake and use of targeted therapies for mRCC in The Netherlands, examine factors associated with the prescription of targeted therapies in daily clinical practice and study their effectiveness in terms of overall survival (OS). METHODS: Two cohorts from PERCEPTION, a population-based registry of mRCC patients, were used: a 2008-2010 Cohort (n = 645) and a 2011-2013 Cohort (n = 233). Chi-squared tests for trend were used to study time trends in the use of targeted therapy. Patients were grouped based on the eligibility criteria of the SUTENT trial, the trial that led to sunitinib becoming standard of care, to investigate the use of targeted therapies amongst patients fulfilling those criteria. Multi-level logistic regression was used to identify patient subgroups that are less likely to receive targeted therapies. RESULTS: Approximately one-third of patients fulfilling SUTENT trial eligibility criteria did not receive any targeted therapy (29 % in the 2008-2010 Cohort; 35 % in the 2011-2013 Cohort). Patients aged 65+ years were less likely to receive targeted therapy in both cohorts and different risk groups (odds ratios range between 0.84-0.92); other factors like number of metastatic sites were of influence in some subgroups. Amongst treated patients, there was a decreasing trend in sunitinib use over time (p = 0.0061), and an increasing trend in pazopanib use (p = 0.0005). CONCLUSIONS: Targeted therapies have largely replaced interferon-alfa as first-line standard of care. Nevertheless, many eligible patients in Dutch daily practice did not receive targeted therapies despite their ability to improve survival. Reasons for their apparent underutilisation should be examined more carefully.

The proportion of postmenopausal breast cancer cases in the Netherlands attributable to lifestyle-related risk factors.

We aimed to estimate the proportion of Dutch postmenopausal breast cancer cases in 2010 that is attributable to lifestyle-related risk factors. We calculated population attributable fractions (PAFs) of potentially modifiable risk factors for postmenopausal breast cancer in Dutch women aged >50 in 2010. First, age-specific PAFs were calculated for each risk factor, based on their relative risks for postmenopausal breast cancer (from meta-analyses) and age-specific prevalence in the population (from national surveys) around the year 2000, assuming a latency period of 10 years. To obtain the overall PAF, age-specific PAFs were summed in a weighted manner, using the age-specific breast cancer incidence rates (2010) as weights. 95 % confidence intervals for PAF estimates were derived by Monte Carlo simulations. Of Dutch women >40 years, in 2000, 51 % were overweight/obese, 55 % physically inactive (<5 days/week 30 min activity), 75 % regularly consumed alcohol, 42 % ever smoked cigarettes and 79 % had a low-fibre intake (<3.4 g/1000 kJ/day). These factors combined had a PAF of 25.7 % (95 % CI 24.2-27.2), corresponding to 2,665 Dutch postmenopausal breast cancer cases in 2010. PAFs were 8.8 % (95 % CI 6.3-11.3) for overweight/obesity, 6.6 % (95 % CI 5.2-8.0) for alcohol consumption, 5.5 % (95 % CI 4.0-7.0) for physical inactivity, 4.6 % (95 % CI 3.3-6.0) for smoking and 3.2 % (95 % CI 1.6-4.8) for low-fibre intake. Our findings imply that modifiable risk factors are jointly responsible for approximately one out of four Dutch postmenopausal breast cancer cases. This suggests that incidence rates can be lowered substantially by living a more healthy lifestyle.

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.

Postprostatectomy ultrasound-guided transrectal implantation of gold markers for external beam radiotherapy. Technique and complications rate.

BACKGROUND AND PURPOSE: Postprostatectomy radiotherapy (RT) improves survival in adjuvant and salvage settings. The implantation technique and complications rate of gold markers in the prostate bed for high-precision RT were analyzed. PATIENTS AND METHODS: Patients undergoing postprostatectomy RT for prostate-specific antigen (PSA) relapse or high-risk disease were enrolled in the study. Under transrectal ultrasound guidance, three fine gold markers were implanted in the prostate bed and the technical difficulties of insertion were documented. Patients received our self-designed questionnaires concerning complications and pain. The influence of anticoagulants and coumarins on bleeding was analyzed, as was the effect of potential risk factors on pain. RESULTS: In 77 consecutive patients, failure of marker implantation or marker migration was seen in six cases. Rectal bleeding was reported by 10 patients and 1 had voiding complaints. No macroscopic hematuria persisting for more than 3 days was observed. Other complications included rectal discomfort (n = 2), nausea (n = 1), abdominal discomfort (n = 1), and pain requiring analgesics (n = 4). No major complications were reported. On a 0-10 visual analogue scale (VAS), the mean pain score was 3.7. No clinically significant risk factors for complications were identified. CONCLUSION: Transrectal implantation of gold markers in the prostate bed is feasible and safe. Alternatives like cone beam computed tomography (CBCT) should be considered, but the advantages of gold marker implantation for high-precision postprostatectomy RT would seem to outweigh the minor risks involved.

Risk of prostate cancer among cancer survivors in the Netherlands.

BACKGROUND: In parallel with increasing numbers of cancer patients and improving cancer survival, the occurrence of second primary cancers becomes a relevant issue. The aim of our study was to evaluate risk of prostate cancer as second primary cancer in a population-based setting. METHODS: Data from the Netherlands Cancer Registry were used to estimate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for prostate cancer as second primary cancer. The effect of time since first cancer diagnosis, specific first cancer sites, age, and pelvic radiotherapy was taken into account. RESULTS: Out of 551,553 male patients diagnosed with a first primary cancer between 1989 and 2008, 9243 patients were subsequently diagnosed with prostate cancer. Overall, cancer survivors showed an increased risk (SIR 1.3, 95% CI 1.2-1.3) of prostate cancer. The increased prostate cancer risk was limited to the first year of follow-up for the majority of the specific first cancer sites. More than 10 years after the first cancer diagnosis, only melanoma patients were at increased risk (SIR 1.5, 95% CI 1.2-1.9), while patients with head or neck cancers were at decreased risk (SIR 0.7, 95% CI 0.5-0.9) of being diagnosed with prostate cancer. Patients who underwent primary pelvic radiotherapy for their first cancer had a decreased risk of prostate cancer in the long term (SIR 0.5, 95% CI 0.4-0.6). CONCLUSIONS: Our data showed that cancer survivors have an increased prostate cancer risk in the first year following a first cancer diagnosis, which is most likely the result of active screening or incidental detection.

Risk and prognostic significance of metachronous contralateral testicular germ cell tumours.

BACKGROUND: Testicular germ cell tumour (TGCT) patients are at increased risk of developing a contralateral testicular germ cell tumour (CTGCT). It is unclear whether TGCT treatment affects CTGCT risk. METHODS: The risk of developing a metachronous CTGCT (a CTGCT diagnosed ≥6 months after a primary TGCT) and its impact on patient's prognosis was assessed in a nationwide cohort comprising 3749 TGCT patients treated in the Netherlands during 1965-1995. Standardised incidence ratios (SIRs), comparing CTGCT incidence with TGCT incidence in the general population, and cumulative CTGCT incidence were estimated and CTGCT risk factors assessed, accounting for competing risks. RESULTS: Median follow-up was 18.5 years. Seventy-seven metachronous CTGCTs were diagnosed. The SIR for metachronous CTGCTs was 17.6 (95% confidence interval (95% CI) 13.9-22.0). Standardised incidence ratios remained elevated for up to 20 years, while the 20-year cumulative incidence was 2.2% (95% CI 1.8-2.8%). Platinum-based chemotherapy was associated with a lower CTGCT risk among non-seminoma patients (hazard ratio 0.37, 95% CI 0.18-0.72). The CTGCT patients had a 2.3-fold (95% CI 1.3-4.1) increased risk to develop a subsequent non-TGCT cancer and, consequently, a 1.8-fold (95% CI 1.1-2.9) higher risk of death than patients without a CTGCT. CONCLUSION: The TGCT patients remain at increased risk of a CTGCT for up to 20 years. Treatment with platinum-based chemotherapy reduces this risk.

[The Dutch Cancer Society Cancer Risk Test]. / De KWF Kanker Risico Test.

The Dutch Cancer Society developed the 'KWF Kanker Risico Test' (Cancer Risk Test) to improve the information available to the Dutch population regarding cancer risk factors. This Internet test, based under licence on the American 'Your Disease Risk' test, informs users about risk factors for 12 common types of cancer. The test provides an estimate of individual risk of a specific type of cancer and gives specific lifestyle advice that could lower that risk. This paper describes the development of the test, how it works, and its strengths and limitations.

DNA adducts in skin biopsies and 1-hydroxypyrene in urine of psoriasis patients and healthy volunteers following treatment with coal tar.

Coal tar ointments (CTO) are frequently used in the treatment of psoriasis and eczema, but CTO contain carcinogenic polycyclic aromatic hydrocarbons (PAH). PAH are absorbed and metabolized in the skin. In psoriasis, the skin barrier is altered and therefore, absorption and metabolism of PAH may differ from healthy skin. In this study, levels of urinary 1-hydroxypyrene and PAH-DNA adducts in the skin were studied in psoriatic patients and healthy volunteers. Three punch biopsies were taken from the lower back of 10 male volunteers and from a psoriatic plaque in 10 male patients. A surface of 6.25 cm(2) was treated with CTO. After 96 h CTO was removed and another three skin biopsies were collected from the treated area. DNA was isolated from skin biopsies and urine was collected during and after the exposure period. After 24h, a twofold lower 1-hydroxypyrene urinary excretion was observed in patients compared to healthy volunteers and after 48 h, this difference reached statistical significance (p<0.05). Over 96 h the median level of the sum of PAH-DNA adducts, analyzed by (32)P-post-labeling, increased from 3.5 before CTO administration to 21.1 adducts per 10(8) nucleotides in volunteers, and from 1.0 to 3.6 adducts per 10(8) nucleotides in patients. At 96 h, PAH-DNA levels were higher in healthy volunteers than in patients (p<0.05). Biomarkers for uptake, bioavailability and bioactivation of PAH were lower in patients compared to volunteers. These data suggest a lower risk of carcinogenic effects of CTO in psoriatic skin compared to healthy skin.

Downstaging of TURBT-Based Muscle-Invasive Bladder Cancer by Radical Cystectomy Predicts Better Survival.

Differences between clinical (cT) and pathological tumor (pT) stage occur often after radical cystectomy (RC) for muscle-invasive bladder cancer. In order to evaluate the impact of downstaging on recurrence and survival, we selected patients from a large, contemporary, population-based series of 1,409 patients with MIBC. We included all patients who underwent RC (N=643) and excluded patients who received (neo)adjuvant therapy, those with known metastasis at time of diagnosis, and those with nonurothelial cell tumors. Disease outcomes were defined as recurrence-free survival (RFS) and relative survival (RS), as a good approximation of bladder cancer-specific survival. After applying the exclusion criteria, 375 patients were eligible for analysis. Tumor downstaging was found to be common after RC; in 99 patients (26.4%), tumor downstaging to non-muscle-invasive stages at RC occurred. Hydronephrosis at baseline and positive lymph nodes at RC occurred significantly less often in these patients. In 62 patients, no tumor was left in the cystectomy specimen. pT stage was pT1 in 20 patients and pTis in 17 patients. Patients with tumor downstaging have about a 30% higher RFS and RS compared to those without. Consequently, tumor downstaging is a favorable marker for prognosis after RC.

Blood lipid levels and prostate cancer risk; a cohort study.

It has been hypothesized that blood lipid levels might be associated with prostate cancer risk. The aim of the present study was to evaluate the association between serum total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides and prostate cancer risk in a cohort study among 2842 Dutch men. By the end of follow-up, 64 incident cases of prostate cancer were identified. Serum total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides were evaluated as potential risk factors for prostate cancer using multivariable Cox proportional hazards regression models. These analyses were restricted to men who never used cholesterol-lowering drugs (2118 men, 43 cases). Higher total and higher LDL cholesterol were significantly associated with an increased risk of prostate cancer (hazards ratios (HR) and 95% confidence interval (CI) per mmol l(-1) were 1.39 (95% CI 1.03-1.88) and 1.42 (95% CI 1.00-2.02), respectively). Similar results were observed for aggressive prostate cancer, whereas for non-aggressive prostate cancer a significant association with HDL cholesterol was found (HR 4.28, 95% CI 1.17-15.67). The results of this study suggest that blood lipid levels may influence risk of prostate cancer. However, the exact roles of different cholesterol fractions on prostate cancer aggressiveness should be further evaluated.

Opportunity for breast cancer screening in limited resource countries: a literature review and implications for Iran.

Young age at occurrence and advanced tumour stage at diagnosis should urge health policy makers to focus on strategies that will help to reduce breast cancer burden in Iran. However, fundamental knowledge to select the optimal control strategy is limited. In this review paper we summarize considerations for launching a successful mass screening program in Iran using a thorough search of the literature focusing on screening activities for breast cancer in limited resource countries (LRCs). The Pubmed and Web of Knowledge databases were used for literature searches with the terms "breast neoplasm' and "screening' in combination with "limited resource countries', or "developing countries'. In addition, the bibliographies of selected references were also searched and utilized. More than 200 articles were found from 2005 to June 2011, of which 96 met the inclusion criteria. Papers were reviewed and categorized as follows: necessity and adoption of screening guidelines in LRCs (n=44); pilot implementation and barriers to screening program in LRCs (n=25); knowledge and attitudes on breast cancer and screening behaviour in LRCs (n=27). The results of the reviewed studies show that the rising trend of breast cancer incidence in LRCs has made it a health priority. Financial constraints to implement mammography screening in LRCs promote the use of alternative but less accurate screening modalities such as physical breast examination. Starting a breast cancer screening program in LRCs faces several challenges related to country's resources status, health service capacity and community awareness. Conservative attitudes toward women, fatalism and misconception on breast cancer risk factors and screening behaviour could seriously prohibit women's participation. In conclusion, given the lack of quantitative information and implementation research on breast cancer control in Iran, our ability to give a clear advice for breast cancer screening in Iran is limited. Iran should adopt a tailor-made strategy for mass screening with great emphasis on reducing the number of advanced stage tumours or "down-staging'. Combination of two approaches, clinical breast examination (CBE) and mammography would be promising given the increased competence of health care professional and public awareness. Equally important, a control plan should be started small and expanded gradually.