BACKGROUND AND OBJECTIVE: The role of genetic variants in response to systemic therapy in muscle-invasive bladder cancer (MIBC) is still elusive. We assessed variations in genes involved in DNA damage repair (DDR) before and after cisplatin-based neoadjuvant chemotherapy (NAC) and correlation of alteration patterns with DNA damage and response to therapy. METHODS: Matched tissue from 46 patients with MIBC was investigated via Ion Torrent-based next-generation sequencing using a self-designed panel of 30 DDR genes. Phosphorylation of γ-histone 2A.X (H2AX) was analyzed via immunohistochemistry to evaluate DNA damage. Genetic variants were analyzed along with clinical data and quantitative phospho-H2AX data using the Kaplan-Meier method, Cox regression analysis, and factor analysis of mixed data. KEY FINDINGS AND LIMITATIONS: Twenty-five patients (54%) had a response (
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- časopisecké články MeSH
BACKGROUND AND OBJECTIVE: Stone size has traditionally been measured in one dimension. This is reflected in most of the literature and in the EAU guidelines. However, recent studies have shown that multidimensional measures provide better prediction of outcomes. METHODS: We performed a systematic review and meta-analysis of the prognostic accuracy of measures of stone size (PROSPERO reference CRD42022346967). We considered all studies reporting prognostic accuracy statistics on any intervention for kidney stones (extracorporeal shockwave lithotripsy [ESWL], ureterorenoscopy [URS], or percutaneous nephrolithotomy [PCNL]; Population) using multiplane measurements of stone burden (area in mm2 or volume in mm3; Intervention) in comparison to single-plane measurements of stone burden (size in mm; Intervention) for the study-defined stone-free rate (Outcome) in a PICO-framed question. We also assessed complication rates (overall and by Clavien-Dindo grade) and the operative time as secondary outcomes. Searches were made between 1970 and August 2023. We used the DeLong method to compare receiver operating characteristic (ROC) curves. KEY FINDINGS AND LIMITATIONS: Of 24 studies included in the review, 12 were eligible for comparative analysis with the DeLong test following meta-analysis of prognostic accuracy. For prediction of stone-free status, the area under the ROC curve (AUC) was significantly higher for stone volume than for stone size (0.71 vs 0.67; p < 0.001). Subanalyses confirmed this for ESWL and URS, but not for PCNL. For URS, the AUC was also significantly higher for stone area than for stone size (0.79 vs 0.77; p < 0.001). Throughout all analyses, there was no difference in AUC between stone area and stone volume. There was high risk of bias for all analyses apart from the URS subanalyses. CONCLUSIONS AND CLINICAL IMPLICATIONS: According to the limited data currently available, stone-free rates are predicted with significantly higher accuracy using multidimensional measures of stone burden in comparison to a single linear measurement. PATIENT SUMMARY: We reviewed different ways of measuring the size of stones in the kidney or urinary tract and compared their accuracy in predicting stone-free rates after treatment. We found that measurement of the stone area (2 dimensions) or stone volume (3 dimensions) is better than stone diameter (1 dimension) in predicting stone-free status after treatment.
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- přehledy MeSH
UNLABELLED: Early recognition of hereditary urological cancers may influence diagnostic and therapeutic decision-making, and potentially alter the fate of patients and family members. Here, we introduce readers to the current knowledge on germline genetic testing and clinical practice in prostate, bladder, renal, and testicular carcinoma. Considering all urological cancer patients, routine inquiries about familial cancer history should become a standard practice in clinical settings. If suspicion arises, patients can opt for two avenues: referral to genetic counseling or undergoing genetic tests after consultation with the treating urologist. PATIENT SUMMARY: Tumors of the urogenital tract (prostate, kidney, bladder, and testes) can sometimes be related to genetic mutations that are present in all the cells of the body. Such mutations can be inherited and run in families. Therefore, it is relevant to obtain information on the incidence of all cancers in the family history. The information obtained may initiate genetic testing, leading to the identification of mutations that are related to cancer in the current or next generation. In addition, these mutations may offer alternative treatment options for patients.
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BACKGROUND: Adverse events induced by intravesical bacillus Calmette-Guérin (BCG) to treat high-grade non-muscle-invasive bladder cancer (NMIBC) often lead to treatment discontinuation. The EAU-RF NIMBUS trial found a reduced number of standard-dose BCG instillations to be inferior with the standard regimen. Nonetheless, it remains important to evaluate whether patients in the reduced BCG treatment arm had better quality of life (QoL) due to a possible reduction in toxicity or burden. OBJECTIVE: To evaluate whether patients in the EAU-RF NIMBUS trial experienced better QoL after a reduced BCG instillation frequency. DESIGN SETTING AND PARTICIPANTS: A total of 359 patients from 51 European sites were randomized to one of two treatment arms between December 2013 and July 2019. The standard frequency arm (n = 182) was 6 weeks of BCG induction followed by 3 weeks of maintenance at months 3, 6, and 12. The reduced frequency arm (n = 177) was BCG induction at weeks 1, 2, and 6, followed by maintenance instillations at weeks 1 and 3 of months 3, 6, and 12. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Analyses were performed using an intention-to-treat analysis and a per-protocol analysis. QoL was measured using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 version 3.0 (QLQ-C30 v.03) prior to the first and last instillations of each BCG cycle. Group differences were determined using linear regression corrected for QoL at baseline. Differences in QoL over time were tested for significance using a linear mixed model. Side effects were recorded by the treating physician using a standardized form. Chi-square tests were used to compare the side-effect frequency between the arms. RESULTS AND LIMITATIONS: There were no significant differences in the means of each QoL scale between the two arms. There were also no significant changes over time in all QoL domains for both arms. However, differences in the incidence of general malaise at T1 (before the last induction instillation), frequency, urgency, and dysuria at T7 (before the last maintenance instillation) were detected in favor of the reduced frequency arm. CONCLUSIONS: Reducing the BCG instillation frequency does not improve the QoL in NMIBC patients despite lower storage symptoms. PATIENT SUMMARY: In this study, we evaluated whether a reduction in the number of received bacillus Calmette-Guérin instillations led to better quality of life in patients with high-grade non-muscle-invasive bladder cancer. We found no difference in the quality of life between the standard and the reduced bacillus Calmette-Guérin instillation frequency. We conclude that reducing the number of instillations does not lead to better quality of life in patients with high-grade non-muscle-invasive bladder cancer.
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UNLABELLED: An updated Council of the EU recommendation on cancer screening was adopted in December 2022 during the Czech EU presidency. The recommendation included prostate cancer as a suitable target disease for organised screening, and invited countries to proceed with piloting and further research. To support further discussions and actions to promote early detection of prostate cancer, an international conference in November 2022 (Prostaforum 2022) resulted in a joint declaration. Here we describe the EU policy background, summarise the preparation of the declaration and the key underlying evidence and expert recommendations, and report the text of the declaration. The declaration summarises the striking inequalities in prostate cancer burden in Europe and calls on all stakeholders to consider and support concrete steps for advancement of organised early detection of prostate cancer. Our aim is to request endorsement of the text and potential initiation of practical actions by all stakeholders to support the aims of the declaration. PATIENT SUMMARY: Prostate cancer is among the most frequent cancers and is one of the most common causes of cancer death among men. The European Union has recommended new pilot programmes for prostate cancer screening. The Prostaforum 2022 declaration invites all stakeholders to support this new recommendation with specific steps.
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BACKGROUND: Grade of non-muscle-invasive bladder cancer (NMIBC) is an important prognostic factor for progression. Currently, two World Health Organization (WHO) classification systems (WHO1973, categories: grade 1-3, and WHO2004 categories: papillary urothelial neoplasm of low malignant potential [PUNLMP], low-grade [LG], high-grade [HG] carcinoma) are used. OBJECTIVE: To ask the European Association of Urology (EAU) and International Society of Urological Pathology (ISUP) members regarding their current practice and preferences of grading systems. DESIGN SETTING AND PARTICIPANTS: A web-based, anonymous questionnaire with ten questions on grading of NMIBC was created. The members of EAU and ISUP were invited to complete an online survey by the end of 2021. Thirteen experts had previously answered the same questions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The submitted answers from 214 ISUP members, 191 EAU members, and 13 experts were analyzed. RESULTS AND LIMITATIONS: Currently, 53% use only the WHO2004 system and 40% use both systems. According to most respondents, PUNLMP is a rare diagnosis with management similar to Ta-LG carcinoma. The majority (72%) would consider reverting back to WHO1973 if grading criteria were more detailed. Separate reporting of WHO1973-G3 within WHO2004-HG would influence clinical decisions for Ta and/or T1 tumors according the majority (55%). Most respondents preferred a two-tier (41%) or a three-tier (41%) grading system. The current WHO2004 grading system is supported by a minority (20%), whereas nearly half (48%) supported a hybrid three- or four-tier grading system composed of both WHO1973 and WHO2004. The survey results of the experts were comparable with ISUP and EAU respondents. CONCLUSIONS: Both the WHO1973 and the WHO2004 grading system are still widely used. Even though opinions on the future of bladder cancer grading were strongly divided, there was limited support for WHO1973 and WHO2004 in their current formats, while the hybrid (three-tier) grading system with LG, HG-G2, and HG-G3 as categories could be considered the most promising alternative. PATIENT SUMMARY: Grading of non-muscle-invasive bladder cancer (NMIBC) is a matter of ongoing debate and lacks international consensus. We surveyed urologists and pathologists of European Association of Urology and International Society of Urological Pathology on their preferences regarding NMIBC grading to generate a multidisciplinary dialogue. Both the "old" World Health Organization (WHO) 1973 and the "new" WHO2004 grading schemes are still used widely. However, continuation of both the WHO1973 and the WHO2004 system showed limited support, while a hybrid grading system composed of both the WHO1973 and the WHO2004 classification system may be considered a promising alternative.
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BACKGROUND: There are currently no guideline recommendations regarding the treatment of cisplatin-ineligible, clinically lymph node-positive (cN+) bladder cancer (BCa). OBJECTIVE: To investigate the oncological efficacy of gemcitabine/carboplatin induction chemotherapy (IC) in comparison to cisplatin-based regimens in cN+ BCa. DESIGN SETTING AND PARTICIPANTS: This was an observational study of 369 patients with cT2-4 N1-3 M0 BCa. INTERVENTION: IC followed by consolidative radical cystectomy (RC). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoints were the pathological objective response (pOR; ypT0/Ta/Tis/T1 N0) rate and the pathological complete response (pCR; ypT0N0) rate. We applied 3:1 propensity score matching (PSM) to reduce selection bias. Overall survival (OS) and cancer-specific survival (CSS) were compared across groups using the Kaplan-Meier method. Associations between the treatment regimen and survival endpoints were tested in multivariable Cox regression analyses. RESULTS AND LIMITATIONS: After PSM, a cohort of 216 patients was available for analysis, of whom 162 received cisplatin-based IC and 54 gemcitabine/carboplatin IC. At RC, 54 patients (25%) had a pOR and 36 (17%) had a pCR. The 2-yr CSS was 59.8% (95% confidence interval [CI] 51.9-69%) for patients who received cisplatin-based IC versus 38.8% (95% CI 26-57.9%) for those who received gemcitabine/carboplatin. For the pOR (p = 0.8), ypN0 status at RC (p = 0.5), and cN1 BCa subgroups (p = 0.7), there was no difference in CSS between cisplatin-based IC and gemcitabine/carboplatin. In the cN1 subgroup, treatment with gemcitabine/carboplatin was not associated with shorter OS (p = 0.2) or CSS (p = 0.1) on multivariable Cox regression analysis. CONCLUSIONS: Cisplatin-based IC seems to be superior to gemcitabine/carboplatin and should be the standard for cisplatin-eligible patients with cN+ BCa. Gemcitabine/carboplatin may be an alternative treatment for selected cisplatin-ineligible patients with cN+ BCa. In particular, selected cisplatin-ineligible patients with cN1 disease may benefit from gemcitabine/carboplatin IC. PATIENT SUMMARY: In this multicenter study, we found that selected patients with bladder cancer and clinical evidence of lymph node metastasis who cannot receive standard cisplatin-based chemotherapy before surgery to remove their bladder may benefit from chemotherapy with gemcitabine/carboplatin. Patients with a single lymph node metastasis may benefit the most.
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BACKGROUND: Testicular germ cell tumors (TGCTs) are the most common malignant tumors in young men. Despite considerable geographic, ethnic, and temporal variations in the incidence of TGCTs, without convincing explanation, incidence rates of TGCTs have been increasing in many countries since, at least, the mid-20th century. OBJECTIVE: To investigate the incidence rates of TGCTs in Austria by analyzing data from the Austrian Cancer Registry. DESIGN SETTING AND PARTICIPANTS: Available data between 1983 and 2018 were provided by the Austrian National Cancer Registry and analyzed retrospectively. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Germ cell tumors derived from germ cell neoplasia in situ were classified into seminomas and nonseminomas. Age-specific incidence rates and age-standardized rates were calculated. Annual percent changes (APCs) and average annual percent changes in incidence rates were determined to describe trends from 1983 to 2018. All statistical analyses were performed using SAS version 9.4 and joinpoint. RESULTS AND LIMITATIONS: The study population consists of 11 705 patients diagnosed with TGCTs. The median age at diagnosis was 37.7 yr. The standardized incidence rate of TGCTs increased significantly (p < 0.0001) from 4.1 (3.4, 4.8) per 100 000 in 1983 to 8.7 (7.9, 9.6) per 100 000 in 2018 by an average APC of 1.74 (1.20, 2.29). The joinpoint regression revealed a change point in time trend in 1995 with an APC of 4.24 (2.77, 5.72) before 1995 and an APC of 0.47 (0.06, 0.89) thereafter. Incidence rates were about twice as high for seminomas as for nonseminomas. A trend analysis by age group showed that the highest TGCT incidence rate was observed among men aged 30-40 yr, with a steep increase before 1995. CONCLUSIONS: The incidence rate of TGCTs increased in Austria over the past decades and appears to have reached a plateau at a high level. A time trend analysis by age group for the overall incidence was highest in men aged 30-40 yr, with a steep increase before 1995. These data should lead to awareness campaigns and research to further investigate the causes of this development. PATIENT SUMMARY: We reviewed the data between 1983 and 2018 provided by the Austrian National Cancer Registry to analyze the incidence and incidence trend in testicular cancer. Testicular cancer shows an increasing incidence in Austria. The overall incidence was highest in men aged 30-40 yr, with a steep increase before 1995. The incidence appears to have reached a plateau at a high level in recent years.
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- časopisecké články MeSH
BACKGROUND: Prostate cancer has a multifaceted treatment pattern. Evidence is lacking for optimal treatment sequences for metastatic castration-resistant prostate cancer (mCRPC). OBJECTIVE: To increase the understanding of real-world treatment pathways and outcomes in patients with mCRPC. DESIGN SETTING AND PARTICIPANTS: A prospective, noninterventional, real-world analysis of 3003 patients with mCRPC in the Prostate Cancer Registry (PCR; NCT02236637) from June 14, 2013 to July 9, 2018 was conducted. INTERVENTION: Patients received first- and second-line hormonal treatment and chemotherapy as follows: abiraterone acetate plus prednisone (abiraterone)-docetaxel (ABI-DOCE), abiraterone-enzalutamide (ABI-ENZA), abiraterone-radium-223 (ABI-RAD), docetaxel-abiraterone (DOCE-ABI), docetaxel-cabazitaxel (DOCE-CABA), docetaxel-enzalutamide (DOCE-ENZA), and enzalutamide-docetaxel (ENZA-DOCE). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Baseline patient characteristics, quality of life, mCRPC treatments, and efficacy outcomes (progression and survival) were presented descriptively. RESULTS AND LIMITATIONS: Data from 727 patients were eligible for the analysis (ABI-DOCE n = 178, ABI-ENZA n = 99, ABI-RAD n = 27, DOCE-ABI n = 191, DOCE-CABA n = 74, DOCE-ENZA n = 116, and ENZA-DOCE n = 42). Demographics and disease characteristics among patients between different sequences varied greatly. Most patients who started on abiraterone or enzalutamide stopped therapy because of disease progression. No randomisation to allow treatment/sequence comparisons limited this observational study. CONCLUSIONS: The real-world PCR data complement clinical trial data, reflecting more highly selected patient populations than seen in routine clinical practice. Baseline characteristics play a role in mCRPC first-line treatment selection, but other factors, such as treatment availability, have an impact. Efficacy observations are limited and should be interpreted with caution. PATIENT SUMMARY: Baseline characteristics appear to have a role in the first-line treatment selection of metastatic castration-resistant prostate cancer in the real-world setting. First-line abiraterone acetate plus prednisone seems to be the preferred treatment option for older patients and those with lower Gleason scores, first-line docetaxel for younger patients and those with more advanced disease, and first-line enzalutamide for patients with fewer metastases and more favourable performance status. The benefit to patients from these observations remains unknown.
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Background: There might be differential sensitivity to neoadjuvant chemotherapy (NAC) in patients with primary muscle-invasive bladder cancer (MIBC) in comparison to patients with secondary MIBC after a history of non-muscle-invasive disease. Objective: To investigate pathologic response rates and survival associated with primary versus secondary MIBC among patients treated with cisplatin-based NAC for cT2-4N0M0 MIBC. Design setting and participants: Oncologic outcomes were compared for 350 patients with primary MIBC and 64 with secondary MIBC treated with NAC and radical cystectomy between 1992 and 2021 at 11 academic centers. Genomic analyses were performed for 476 patients from the Memorial Sloan Kettering/The Cancer Genome Atlas cohort. Outcome measurements and statistical analysis: The outcome measures were pathologic objective response (pOR; ≤ypT1 N0), pathologic complete response (pCR; ypT0 N0), overall mortality, and cancer-specific mortality. Results and limitations: The primary MIBC group had higher pOR (51% vs 34%; p = 0.02) and pCR (33% vs 17%; p = 0.01) rates in comparison to the secondary MIBC group. On multivariable logistic regression analysis, primary MIBC was independently associated with both pOR (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.26-0.87; p = 0.02) and pCR (OR 0.41, 95% CI 0.19-0.82; p = 0.02). However, on multivariable Cox regression analysis, primary MIBC was not associated with overall mortality (hazard ratio 1.70, 95% CI 0.84-3.44; p = 0.14) or cancer-specific mortality (hazard ratio 1.50, 95% CI 0.66-3.40; p = 0.3). Genomic analyses revealed a significantly higher ERCC2 mutation rate in primary MIBC than in secondary MIBC (12.4% vs 1.3%; p < 0.001). Conclusions: Patients with primary MIBC have better pathologic response rates to NAC in comparison to patients with secondary MIBC. Chemoresistance might be related to the different genomic profile of primary versus secondary MIBC. Patient summary: We investigated the treatment response to neoadjuvant chemotherapy (NAC; chemotherapy received before the primary course of treatment) and survival for patients with a primary diagnosis of muscle-invasive bladder cancer (MIBC) in comparison to patients with a history of non-muscle-invasive bladder cancer that progressed to MIBC. Patients with primary MIBC had a better response to NAC but this did not translate to better survival after accounting for other tumor characteristics.
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