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01 juli 2023, Item does not contain fulltext, CONTEXT: The optimal management for men with prostate cancer (PCa) with unconventional histology (UH) is unknown. The outcome for these cancers might be worse than for conventional PCa and so different approaches may be needed. OBJECTIVE: To compare oncological outcomes for conventional and UH PCa in men with localized disease treated with curative intent. EVIDENCE ACQUISITION: A systematic review adhering to the Referred Reporting Items for Systematic Reviews and Meta-Analyses was prospectively registered on PROSPERO (CRD42022296013) was performed in July 2021. EVIDENCE SYNTHESIS: We screened 3651 manuscripts and identified 46 eligible studies (reporting on 1 871 814 men with conventional PCa and 6929 men with 10 different PCa UHs). Extraprostatic extension and lymph node metastases, but not positive margin rates, were more common with UH PCa than with conventional tumors. PCa cases with cribriform pattern, intraductal carcinoma, or ductal adenocarcinoma had higher rates of biochemical recurrence and metastases after radical prostatectomy than for conventional PCa cases. Lower cancer-specific survival rates were observed for mixed cribriform/intraductal and cribriform PCa. By contrast, pathological findings and oncological outcomes for mucinous and prostatic intraepithelial neoplasia (PIN)-like PCa were similar to those for conventional PCa. Limitations of this review include low-quality studies, a risk of reporting bias, and a scarcity of studies that included radiotherapy. CONCLUSIONS: Intraductal, cribriform, and ductal UHs may have worse oncological outcomes than for conventional and mucinous or PIN-like PCa. Alternative treatment approaches need to be evaluated in men with these cancers. PATIENT SUMMARY: We reviewed the literature to explore whether prostate cancers with unconventional growth patterns behave differently to conventional prostate cancers. We found that some unconventional growth patterns have worse outcomes, so we need to investigate if they nee

Item does not contain fulltext, BACKGROUND: Germline and tumour genetic testing in prostate cancer (PCa) is becoming more broadly accepted, but testing indications and clinical consequences for carriers in each disease stage are not yet well defined. OBJECTIVE: To determine the consensus of a Dutch multidisciplinary expert panel on the indication and application of germline and tumour genetic testing in PCa. DESIGN SETTING AND PARTICIPANTS: The panel consisted of 39 specialists involved in PCa management. We used a modified Delphi method consisting of two voting rounds and a virtual consensus meeting. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Consensus was reached if ≥75% of the panellists chose the same option. Appropriateness was assessed by the RAND/UCLA appropriateness method. RESULTS AND LIMITATIONS: Of the multiple-choice questions, 44% reached consensus. For men without PCa having a relevant family history (familial PCa/BRCA-related hereditary cancer), follow-up by prostate-specific antigen was considered appropriate. For patients with low-risk localised PCa and a family history of PCa, active surveillance was considered appropriate, except in case of the patient being a BRCA2 germline pathogenic variant carrier. Germline and tumour genetic testing should not be done for nonmetastatic hormone-sensitive PCa in the absence of a relevant family history of cancer. Tumour genetic testing was deemed most appropriate for the identification of actionable variants, with uncertainty for germline testing. For tumour genetic testing in metastatic castration-resistant PCa, consensus was not reached for the timing and panel composition. The principal limitations are as follows: (1) a number of topics discussed lack scientific evidence, and therefore the recommendations are partly opinion based, and (2) there was a small number of experts per discipline. CONCLUSIONS: The outcomes of this Dutch consensus meeting may provide further guidance on genetic counselling and molecular testing related to PCa.

Contains fulltext : 297151.pdf (Publisher’s version ) (Closed access), AIM: Substantial variation in Gleason grading (GG) of prostate cancer (PCa) exists between Dutch pathology laboratories. This study investigates its impact on treatment strategies. METHODS: Pathology reports of prostate needle biopsies and clinical data of patients with PCa diagnosed between 2017 and 2019 were retrieved from the Dutch nationwide network and registry of histopathology and cytopathology and The Netherlands Cancer Registry. We investigated the impact of grading variation on treatment strategy for patients whose grade was decisive in treatment choice. First, we evaluated the effect of grading practice (low, average or high grading) on active treatment (AT) versus active surveillance in patients with prostate-specific antigen (PSA) <10 ng/mL and cT1c/cT2a disease. Second, we assessed the association of grading practice with performance of pelvic lymph node dissection (PLND) in patients with PSA 10-20 ng/mL or cT2b disease. We used multivariable logistic regression to analyse the relation between laboratories' grading practices and AT or PLND. RESULTS: We included 30 509 patients. GG was decisive in treatment strategy for 11 925 patients (39%). AT was performed significantly less often in patients diagnosed by laboratories that graded lower than average (OR=0.77, 95% CI 0.68 to 0.88). Conversely, patients received AT significantly more often when diagnosed in high-grading laboratories versus average-grading laboratories (OR=1.21, 95% CI 1.03 to1.43). PLND was performed significantly less often in patients diagnosed by low-grading versus average-grading laboratories (OR=0.66, 95% CI 0.48 to 0.90). CONCLUSION: Our study shows that the odds that a patient undergoes AT or PLND, depends on laboratories' grading practices in a substantial number of patients. This likely influences patient prognosis and outcome, necessitating standardisation of GG to prevent suboptimal patient outcome.

Contains fulltext : 215783.pdf (publisher's version ) (Closed access), BACKGROUND: There is uncertainty in deferred active treatment (DAT) programmes, regarding patient selection, follow-up and monitoring, reclassification, and which outcome measures should be prioritised. OBJECTIVE: To develop consensus statements for all domains of DAT. DESIGN, SETTING, AND PARTICIPANTS: A protocol-driven, three phase study was undertaken by the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Association of Urology Section of Urological Research (ESUR)-International Society of Geriatric Oncology (SIOG) Prostate Cancer Guideline Panel in conjunction with partner organisations, including the following: (1) a systematic review to describe heterogeneity across all domains; (2) a two-round Delphi survey involving a large, international panel of stakeholders, including healthcare practitioners (HCPs) and patients; and (3) a consensus group meeting attended by stakeholder group representatives. Robust methods regarding what constituted the consensus were strictly followed. RESULTS AND LIMITATIONS: A total of 109 HCPs and 16 patients completed both survey rounds. Of 129 statements in the survey, consensus was achieved in 66 (51%); the rest of the statements were discussed and voted on in the consensus meeting by 32 HCPs and three patients, where consensus was achieved in additional 27 statements (43%). Overall, 93 statements (72%) achieved consensus in the project. Some uncertainties remained regarding clinically important thresholds for disease extent on biopsy in low-risk disease, and the role of multiparametric magnetic resonance imaging in determining disease stage and aggressiveness as a criterion for inclusion and exclusion. CONCLUSIONS: Consensus statements and the findings are expected to guide and inform routine clinical practice and research, until higher levels of evidence emerge through prospective comparative studies and clinical trials. PATIENT

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Item does not contain fulltext, Background:After treatment with cisplatin-based chemotherapy for testicular cancer (TC), patients have higher prevalence of cardiovascular complications after long-term follow up. Little is known about acute cardiovascular effects of cisplatin-based chemotherapy. The aim of this study was to explore acute effects of chemotherapy on cardiac function in patients treated for TC.Methods:Fourteen TC patients (age 34.6+/-12.3 years) were studied before and 3 months after start with cisplatin-based chemotherapy. Cardiac function was assessed with magnetic resonance imaging. Fasting glucose and insulin levels were measured and insulin sensitivity, reflected by the quantitative insulin sensitivity index (Quicki index), was calculated.Results:Left ventricular (LV) end-diastolic volume and LV stroke volume (SV) significantly decreased from 192+/-27 to 175+/-26 ml (P<0.05) and 109+/-18 to 95+/-16 ml (P<0.05), respectively. The ratio of early and atrial filling velocities across the mitral valve, a parameter of diastolic heart function, decreased after chemotherapy from 1.87+/-0.43 to 1.64+/-0.45 (P<0.01). Metabolic parameters were unfavourably changed, reflected by a decreased Quicki index, which reduced from 0.39+/-0.05 to 0.36+/-0.05 (P<0.05).Conclusion:Chemotherapy for TC induces acute alterations in diastolic heart function, paralleled by unfavourable metabolic changes. Therefore, early after chemotherapy, metabolic treatment may be indicated to possibly reduce long-term cardiovascular complications.