Targeting Androgen Receptor Alterations in Metastatic Prostate Cancer.

There have been significant advances in our understanding of the biology of metastatic prostate cancer (mPCa) and its response to therapy. Androgen receptor (AR) alterations, including mutations, amplifications, splice variants, and alternative activations, play a significant role in mPCa resistance to treatment. Recent studies indicate that AR alterations detected via genomic testing can be considered predictive biomarkers in men with castration-resistant PCa and can guide treatment strategies. Novel therapeutic approaches, including AR antagonists and inhibitors of ACK1, the AR N-terminal domain, or cytochrome P450 11A1, have shown promise in overcoming treatment resistance. Ongoing clinical trials are exploring the efficacy of these treatments in relation to AR mutation status and could potentially transform the treatment landscape for mPCa. PATIENT SUMMARY: Our mini review highlights advances in the treatment of metastatic prostate cancer, with a focus on drugs that target genetic alterations affecting a protein called the androgen receptor. Some promising results have been obtained and clinical trials are ongoing.

Can We Go beyond Pathology? The Prognostic Role of Risk Scoring Tools for Cancer-Specific Survival of Patients with Bladder Cancer Undergoing Radical Cystectomy.

Radical cystectomy (RC) remains a mainstay surgical treatment for non-metastatic muscle-invasive and BCG-unresponsive bladder cancer. Various perioperative scoring tools assess comorbidity burden, complication risks, and cancer-specific mortality (CSM) risk. We investigated the prognostic value of these scores in patients who underwent RC between 2015 and 2021. Cox proportional hazards were used in survival analyses. Risk models' accuracy was assessed with the concordance index (C-index) and area under the curve. Among 215 included RC patients, 63 (29.3%) died, including 53 (24.7%) cancer-specific deaths, with a median follow-up of 39 months. The AJCC system, COBRA score, and Charlson comorbidity index (CCI) predicted CSM with low accuracy (C-index: 0.66, 0.65; 0.59, respectively). Multivariable Cox regression identified the AJCC system and CCI > 5 as significant CSM predictors. Additional factors included the extent of lymph node dissection, histology, smoking, presence of concomitant CIS, and neutrophil-to-lymphocyte ratio, and model accuracy was high (C-index: 0.80). The internal validation of the model with bootstrap samples revealed its slight optimism of 0.06. In conclusion, the accuracy of the AJCC staging system in the prediction of CSM is low and can be improved with the inclusion of other pathological data, CCI, smoking history and inflammatory indices.

(A)voiding misdiagnosis: prediction of detrusor underactivity vs. bladder outlet obstruction using pre-urodynamic nomogram in male patients with LUTS.

PURPOSE: Our study aimed to develop a noninvasive model using a combination of the set of clinical data and uroflowmetry (UFL) to differentiate between detrusor underactivity (DU) and bladder outlet obstruction (BOO) in non-neurogenic male patients with lower urinary tract symptoms (LUTS). METHODS: Data from 229 men with LUTS, diagnosed with DU or BOO on a pressure-flow study (PFS), were retrospectively analyzed, including medical history, Core Lower Urinary Tract Symptoms score (CLSS) questionnaire, UFL and PFS. Uni- and multivariate logistic regression were utilized for the prediction analyses. RESULTS: Of the cohort, 128 (55.9%) patients were diagnosed with DU. A multivariate logistic regression analysis identified less prevalent nocturia (OR 0.27, p < 0.002), more prevalent intermittency (OR 2.33, p = 0.03), less prevalent weak stream (OR 0.14, p = 0.0004), lower straining points in CLSS (OR 0.67, p = 0.02), higher slow stream points in CLSS (OR 1.81, p = 0.002), higher incomplete emptying points in CLSS (OR 1.31, p < 0.02), lower PVR ratio (OR 0.20, p = 0.03), and present features of fluctuating (OR 2.00, p = 0.05), fluctuating-intermittent (OR 3.09, p < 0.006), and intermittent (OR 8.11, p = 0.076) UFL curve shapes as independent predictors of DU. The above prediction model demonstrated satisfactory accuracy (c-index of 0.783). CONCLUSION: Our 10-factor model provides a noninvasive approach to differentiate DU from BOO in male patients with non-neurogenic LUTS, offering a valuable alternative to invasive PFS.

Changes in the Urinary Microbiome After Transurethral Resection of Non-muscle-Invasive Bladder Cancer: Insights from a Prospective Observational Study.

BACKGROUND: This study aimed to characterize the urinary and tumor microbiomes in patients with non-muscle-invasive bladder cancer (NMIBC) before and after transurethral resection of the bladder tumor (TURBT). METHODS: This single-center prospective study included 26 samples from 11 patients with low-grade Ta papillary NMIBC. Urine samples were collected at the index TURBT and at a 1-year follow-up cystoscopy. The metagenomic analysis of bacterial and archaeal populations was performed based on the highly variable V3-V4 region of the 16S rRNA gene. RESULTS: Phylogenetic alpha diversity of the bladder microbiome detected in urine was found to be lower at the 1-year follow-up cystoscopy compared to the time of the index TURBT (p < 0.01). Actinomyces, Candidatus cloacimonas, Sphingobacterium, Sellimonas, Fusobacterium, and Roseobacter were more differentially enriched taxa in urine at the follow-up cystoscopy than at the index TURBT. Beta diversity of urine microbiome significantly changed over time (p < 0.05). Phylogenetic alpha diversity of the microbiome was greater in tumor tissues than in paired urine samples (p<0.01). Sphingomonas, Acinetobacter, Candidatus, and Kocuria were more differentially overrepresented in tumor tissues than in urine. The enrichment of the abundance of Corynebacterium and Anaerococcus species in urine collected at TURBT was observed in patients who experienced recurrence within the follow-up period. CONCLUSIONS: In patients with low-grade NMIBC, the urine microbiome undergoes changes over time after removal of the tumor. The microbiome detected in tumor tissues is more phylogenetically diverse than in paired urine samples collected at TURBT. The interplay between bladder microbiome, tumor microbiome, and their alterations requires further studies to elucidate their predictive value and perhaps therapeutic implications.

Oncologic outcomes of patients treated with kidney-sparing surgery or radical nephroureterectomy for upper urinary tract urothelial cancer: a population-based study.

PURPOSE: Although kidney-sparing surgery (KSS) is a nonminor option for low-risk upper urinary tract urothelial cancer (UTUC), its oncological benefits in high-risk UTUC remain unclear when compared to radical nephroureterectomy (RNU). This study aimed to compare the oncological outcomes of RNU and KSS in patients with UTUC. METHODS: We searched the SEER database for patients treated for primary non-metastatic UTUC with either RNU or a kidney-sparing approach (segmental ureterectomy (SU) or local tumor excision (LTE)) between 2004 and 2018. RESULTS: The study included 6,659 patients with primary non-metastatic UTUC treated with surgery; 2,888 (43.4%) and 3,771 (56.6%) patients presented with ureteral and renal pelvicalyceal tumors, respectively. Finally, 5,479 (82.3%) patients underwent RNU, 799 (12.0%) were treated with SU, and 381 (5.7%) patients received LTE. For confounder control, propensity score matching (PSM) of patients treated with SU and RNU was performed to adjust for T stage, grade, age, gender, tumor size, and lymphadenectomy performance. PSM analysis included 694 patients treated with RNU and 694 individuals who underwent SU. In multivariable Cox regression and Kaplan-Meier analyses, we found no difference in either CSS or OS between RNU and SU, even in the subgroup of high-grade and/or muscle-invasive UTUC including pT3-T4 tumors (all p > 0.05). CONCLUSION: In this population-based study, SU provides equivalent CSS and OS compared to RNU, even in high-risk and locally advanced ureteral cancer. Due to the unavoidable risk of selection bias, further prospective studies are expected to overcome the limitations of this study and support the wider implementation of KSS.

Upper Urinary Tract Urothelial Cancer After Radical Cystectomy for Bladder Cancer: Survival Outcomes After Radical Nephroureterectomy.

BACKGROUND: Systemic and local recurrences of urothelial bladder cancer (UBC) significantly impair survival after radical cystectomy (RC), but little is known about the impact of the recurrence of urothelial cancer in the upper urinary tract (UTUC). This report describes survival outcomes and their predictors for patients who underwent RC followed by radical nephroureterectomy (RNU) for UTUC. METHODS: The Surveillance, Epidemiology, and End Results database was queried to identify patients who underwent RC for UBC and subsequent RNU for UTUC. The Kaplan-Meier method and competing-risk Cox regression (CRR) were used for the survival analysis. RESULTS: Overall, 102 patients have undergone RNU within a median of 49 months (interquartile range [IQR], 27-76 months) since RC. Muscle-invasive UTUCs were predominant at RNU (n = 58; 56.7%), but organ-confined bladder tumors were most frequent at RC (n = 42, 41.5%). After RNU, the estimated 5-year overall survival (OS) was 25.9%, the cancer-specific survival (CSS) was 35.6%, the median OS was 23 months (IQR, 11-63 months), and the CSS was 34 months (IQR, 13-132 months). In the multivariable CRR, the factors predictive for CSS after RNU included male gender (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.03-5.42; p < 0.05), muscle-invasive UTUC (HR, 2.20; 95% CI, 1.13-4.28; p < 0.05), and the presence of distant metastasis (HR,11.59; 95% CI, 5.33-25.2; p < 0.001). CONCLUSIONS: In conclusion, the patients who underwent RNU for UTUC after RC for UBC experienced poor OS and CSS. The majority of RNUs were performed for locally advanced tumors. The independent risk factors for worse OS and CSS after RNU were UTUC T stage, presence of metastasis, and male gender.

Prostate Cancer in Transplant Receivers-A Narrative Review on Oncological Outcomes.

Prostate cancer (PCa) is a low tumor mutational burden (TMB) cancer with a poor response to immunotherapy. Nonetheless, immunotherapy can be useful, especially in metastatic castration-resistant PCa (mCRPC). Increased cytotoxic T lymphocytes (CTLs) density is correlated with a shorter overall survival (OS), an early biochemical relapse, and a generally poor PCa prognosis. An increased number of CCR4+ regulatory T cells (CCR4 + Tregs) relates to a higher Gleason score or earlier progression. The same therapeutic options are available for renal transplant recipients (RTRs) as for the population, with a comparable functional and oncological outcome. Radical retropubic prostatectomy (RRP) is the most common method of radical treatment in RTRs. Brachytherapy and robot-assisted radical prostatectomy (RARP) seem to be promising therapies. Further studies are needed to assess the need for prostatectomy in low-risk patients before transplantation. The rate of adverse pathological features in RTRs does not seem to differ from those observed in the non-transplant population and the achieved cancer control seems comparable. The association between PCa and transplantation is not entirely clear. Some researchers indicate a possible association between a more frequent occurrence of PCa and a worse prognosis in advanced or metastatic PCa. However, others claim that the risk and survival prognosis is comparable to the non-transplant population.

The Association between Lymph Node Dissection and Survival in Lymph Node-Negative Upper Urinary Tract Urothelial Cancer.

The benefit of lymph node dissection (LND) during radical nephroureterectomy (RNU) in lymph node (LN)-negative (cN0/pN0) UTUC remains controversial. We aimed to assess the association between LND and its extent and survival in LN-negative UTUC. The Surveillance, Epidemiology, and End Results database was searched to identify patients with non-metastatic chemotherapy-naïve cN0/pNx or pN0 UTUC who underwent RNU +/- LND between 2004 and 2019. Overall, 4649 patients with cN0/pNx or pN0 UTUC were analyzed, including 909 (19.55%) individuals who had LND. Among them, only in 368 patients (7.92%) was LND extended to at least four LNs, and the remaining 541 patients (11.64%) have had < four LNs removed. In the whole cohort, LND contributed to better cancer-specific survival (CSS) and overall survival (OS). Furthermore, a propensity score-matched analysis adjusted for confounders confirmed that improved CSS and OS was achieved only when ≥ four LNs had been removed, especially in muscle-invasive UTUC. A multivariable analysis further confirmed an association between the extent of LND and CSS. To conclude, adequate LND during RNU was associated with improved OS and CSS in LN-negative UTUC, particularly in muscle-invasive stage. This underscores that a sufficient LN yield is required to reveal a therapeutic benefit in patients undergoing RNU.

Cancer-Specific Survival of Patients with Non-Muscle-Invasive Bladder Cancer: A Population-Based Analysis.

BACKGROUND AND PURPOSE: Non-muscle-invasive bladder cancer (NMIBC) constitutes a heterogeneous group of tumors with different prognoses. This population-based study aimed to report real-world cancer-specific survival (CSS) of NMIBC and create a prognostic nomogram based on the identified risk factors. METHODS: The Surveillance, Epidemiology, and End Results database was searched for patients diagnosed with NMIBC from 2004 to 2015, who underwent transurethral resection of the bladder tumor. The dataset was divided into development and validation cohorts. Factors associated with CSS were identified using Cox proportional hazards and used to develop a prognostic nomogram. RESULTS: In total, 98,238 patients with NMIBC were included. At the median follow-up of 124 months (IQR 81-157 months), cancer-specific mortality (CSM) was highest for T1HG (19.52%), followed by Tis (15.56%), similar for T1LG and TaHG (10.88% and 9.23%, respectively), and lowest for TaLG (3.76%). Multivariable Cox regression for CSS prediction was utilized to develop a nomogram including the following risk factors: tumor T category and grade, age, tumor size and location, histology type, primary character, race, income, and marital status. In the validation cohort, the model was characterized by an AUC of 0.824 and C-index that reached 0.795. CONCLUSIONS: To conclude, NMIBC is associated with a significant risk of long-term CSM especially, but not only, in patients with T1HG. Rarely diagnosed TaHG and T1LG tumors should be regarded as high-risk due to approximately 10% CSM. T category, grading, and age remain the most powerful determinants of CSS in NMIBC, but sociodemographic factors might also influence its prognosis.

Survival outcomes of patients treated with local therapy for nonmetastatic prostate cancer with high prostate-specific antigen concentrations.

BACKGROUND: Patients with nonmetastatic prostate cancer (nmPCa) and high prostate-specific antigen (PSA) levels due to the high likelihood of metastasis pose a clinical dilemma regarding their optimal treatment and long-term outcomes after initial local therapy. We aimed to evaluate the oncologic outcomes of patients treated with radical prostatectomy (RP) or radiotherapy (RT) for nmPCa with high PSA levels. METHODS: We queried the Surveillance, Epidemiology, and End Results (SEER) database to identify patients diagnosed with nmPCa who received RP or RT from 2004 through 2015. We included nmPCa patients with high PSA levels categorized as ≥50 and ≥98 ng/mL, the highest level recorded in SEER. We used the Kaplan-Meier method and Cox proportional hazards to analyze cancer-specific (CSS) and overall survival (OS). RESULTS: We included 6177 patients with nmPCa and PSA ≥ 50 ng/mL at diagnosis; 1698 (27%) had PSA ≥ 98 ng/mL. Of these, 1658 (26.8%) underwent RP and 4519 (73.16%) patients received primary RT. Within a median of 113 months (interquartile range 74-150 months), the 5- and 10-year CSS estimates were 92.3% and 81.5% respectively; 10-year OS was 61%. In the PSA ≥ 98 ng/mL subgroup 5- and 10-year CSS estimates were 89.2% and 76%, respectively. In multivariable analyses for CSS, ISUP grade group (p < 0.001), N stage (p < 0.001), treatment with RP (hazard ratio [HR] = 0.60, 95% confidence interval [CI] 0.43-0.83, p < 0.001), and patient's age (p < 0.05) were associated with improved CSS. In the whole cohort of patients with PSA ≥ 50 ng/mL and RP subgroup, PSA failed to retain its independent prognostic value for CSS. CONCLUSIONS: Patients treated with local therapy for nmPCa with very high PSA at diagnosis have relatively good long-term oncological outcomes. Therefore, among well-selected patients with nmPCa, high PSA levels alone should not preclude the use of radical local therapy. Potential selection bias limits inferences about the relative effectiveness of specific local therapies in this setting.

The prediction of cancer-specific mortality in T1 non-muscle-invasive bladder cancer: comparison of logistic regression and artificial neural network: a SEER population-based study.

PURPOSE: To identify the risk factors for 5-year cancer-specific (CSS) and overall survival (OS) and to compare the accuracy of logistic regression (LR) and artificial neural network (ANN) in the prediction of survival outcomes in T1 non-muscle-invasive bladder cancer. METHODS: This is a population-based analysis using the Surveillance, Epidemiology, and End Results database. Patients with T1 bladder cancer (BC) who underwent transurethral resection of the tumour (TURBT) between 2004 and 2015 were included in the analysis. The predictive abilities of LR and ANN were compared. RESULTS: Overall 32,060 patients with T1 BC were randomly assigned to training and validation cohorts in the proportion of 70:30. There were 5691 (17.75%) cancer-specific deaths and 18,485 (57.7%) all-cause deaths within a median of 116 months of follow-up (IQR 80-153). Multivariable analysis with LR revealed that age, race, tumour grade, histology variant, the primary character, location and size of the tumour, marital status, and annual income constitute independent risk factors for CSS. In the validation cohort, LR and ANN yielded 79.5% and 79.4% accuracy in 5-year CSS prediction respectively. The area under the ROC curve for CSS predictions reached 73.4% and 72.5% for LR and ANN respectively. CONCLUSIONS: Available risk factors might be useful to estimate the risk of CSS and OS and thus facilitate optimal treatment choice. The accuracy of survival prediction is still moderate. T1 BC with adverse features requires more aggressive treatment after initial TURBT.

Magnetic resonance imaging (MRI) for local staging before salvage radical prostatectomy: a meta-analysis.

PURPOSE: The reliability of magnetic resonance imaging (MRI) as a local and nodal staging tool in radio-recurrent prostate cancer (PCa) is still unclear. The present study aims at evaluating the predictive value of MRI in the detection of extracapsular extension (ECE), seminal vesical invasion (SVI) and nodal involvement (LNI) in patients after primary radio (EBRT) and/or brachytherapy (BT) before salvage radical prostatectomy (SRP). METHODS: This systematic review and meta-analysis were performed in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Pubmed, Scopus, and Web of Science databases were systemically reviewed to extract the data on diagnostic performance of MRI in radio-recurrent PCa. RESULTS: Four studies comprising 94 radio-recurrent PCa patients were included. The pooled prevalence of ECE, SVI, and LNI was 61%, 41%, and 20%, respectively. The pooled sensitivity for ECE, SVI and LNI detection was 53% (CI 95% 19.8-83.6%), 53% (CI 95% 37.2-68%) and 33% (CI 95% 4.7-83.1%) respectively, whereas specificity was 75% (CI 95% 40.6-92.6%), 88% (CI 95% 71.7-95.9%) and 92% (CI 95% 79.6-96.8%). The sensitivity analysis revealed that a single outlying study using only T2-weighted imaging instead of multiparametric MRI reported significantly higher sensitivity with significantly lower specificity. CONCLUSIONS: This is the first meta-analysis reporting reliability of staging MRI in a radio-recurrent setting. MRI provides poor sensitivity while maintaining high specificity for local and nodal staging before SRP. However, current evidence is limited to the low number of heterogenous studies at meaningful risk of bias.

Not as black as it is painted? The impact of the first wave of COVID-19 pandemic on surgical treatment of urological cancer patients in Poland - a cross-country experience.

Introduction: In the majority of Western European countries, the coronavirus disease (COVID-19) pandemic has led to a dramatic reduction in urooncological surgeries. Our objective was to evaluate the impact of the pandemic on volume and patterns of urooncological surgery in Poland. Material and methods: This is a retrospective analysis of 10 urologic centres in Poland. Data regarding major oncological procedures performed after the COVID-19 pandemic outbreak (March 15, 2020 - May 31, 2020) were evaluated and compared with data from the respective period in 2019. Results: Between March 15, 2020 and May 31, 2020, a total of 968 oncological procedures were performed in participating centres. When compared to the respective period in 2019 (1063 procedures) the overall number of surgeries declined by 8.9%. The reduction was observed for transurethral resection of bladder tumour (TURBT) (20.1%) and partial nephrectomies (PN) (16.5%). Surgical activity considering radical nephrectomy (RN), nephroureterectomy (NU), and radical prostatectomy (RP) remained relatively unchanged, whereas radical cystectomy (RC) burden showed a significant increase (90.9%). Characteristics of patients treated with TURBT, RC, NU, PN, and RN did not differ significantly between the compared periods, whereas RP in the COVID-19 period was performed more frequently in patients with a higher grade group (p = 0.028) and positive digital rectal examination (p = 0.007). Conclusions: Surgical activity for urological cancers in Poland has been maintained during the first wave of the COVID-19 pandemic. The Polish strategy in the initial period of the COVID-19 crisis mirrors the scenario of hard initial lockdown followed by adaptive lockdown, during which oncological care remained undisrupted and did not require particular priority triage.

The Cannabinoid Ligand Arachidonyl-2'-Chloroethylamide (ACEA) Ameliorates Depressive and Overactive Bladder Symptoms in a Corticosterone-Induced Female Wistar Rat Model.

There is growing need to increase the knowledge on the cannabinoid ligands in the treatment of overactive bladder. Among potential candidates, arachidonyl-2'-chloroethylamide (ACEA), a selective cannabinoid CB1 receptor agonist is proposed. The aim of this paper was to determine if ACEA, a selective cannabinoid CB1 receptor agonist, could reverse the effects of corticosterone (CORT), characteristic of depressive and bladder overactivity potential. The animals (48 female rats) were divided into four groups: I-control, II-received CORT, III-received ACEA, and IV-received the combination of CORT and ACEA. The conscious cystometry, forced swim test (FST), and locomotor activity measurements were performed 3 days after the last dose of ACEA, followed by ELISA measurements. In group IV, ACEA restored urodynamic parameters that were altered by CORT. CORT prolonged the immobility time in FST and the values were lowered by ACEA. ACEA normalized the expression of c-Fos in all the analyzed central micturition centers (group IV vs. group II). ACEA restored the CORT-induced changes in the biomarkers in urine (BDNF, NGF), bladder detrusor (VAChT, Rho kinase), bladder urothelium (CGRP, ATP, CRF, OCT-3, TRPV1), and hippocampus (TNF-α, IL-1ß and Il-6, CRF, IL-10, BDNF, NGF). In conclusion, ACEA was proven to reverse CORT-induced changes in both cystometric and biochemical parameters that are determinants of OAB/depression, which represents an example of an existing link between OAB and depression via cannabinoid receptors.

Neutrophil-to-lymphocyte ratio predicts nodal involvement in unfavourable, clinically nonmetastatic prostate cancer patients and overall survival in pN1 patients.

The aim of our study was to determine the clinical utility of neutrophil-to-lymphocyte ratio (NLR) in predicting presence and prognosis of nodal involvement in patients treated with radical prostatectomy (RP) due to prostate cancer. This single-centre retrospective study included 205 patients treated with RP and lymphadenectomy between 2012 and 2018. Logistic regression and Kaplan-Meier analyses were performed to evaluate the prognostic value of preoperative NLR in terms of nodal spread and survival. Patients staged pN1 presented lower mean NLR (2.53 vs 3.86; p = 0.0025) compared to pN0 patients. On multivariable analysis of different haematological markers, only NLR exceeding the median (≥ 2.7) predicted pN1 (OR = 0.38; p = 0.0367) independently of biopsy grading and PSA. In internal validation (n = 31 pN1, n = 174 pN0) on the bootstrapped dataset using a spare cutoff of NLR ≥ 4.1 would allow sparing lymphadenectomy in 22.09% pN0 patients, missing 6.45% pN1 (NPV 92.66%; 95% CI 84.91-100%). Noticeably, in pN1 patients NLR ≥ 2.7 correlated with shorter overall survival (p = 0.0196), despite its association with reduced risk of pN1. High pre-prostatectomy NLR was negatively associated with pN1, yielding high NPV in internal validation. Simultaneously, high NLR in pN1 patients was associated with shorter survival.

The impact of smoking on recurrence and progression of non-muscle invasive bladder cancer: a systematic review and meta-analysis.

OBJECTIVES: Although smoking is a well-recognized causative factor of urothelial bladder cancer and accounts for 50% of cases, less is known about the prognostic significance of smoking on non-muscle invasive bladder cancer (NMIBC) prognosis. This systematic review and meta-analysis aimed to evaluate the effect of smoking on the risk of NMIBC recurrence and progression. MATERIALS AND METHODS: We systematically searched Medline, Web of Science and Scopus databases for original articles published before October 2021 regarding the effect of smoking on NMIBC recurrence and progression. Information about smoking status and the number of events or odds ratio or hazard ratio for event-free survival must have been reported to include the study in the analysis. Quality In Prognosis Studies tool was utilized for the risk of bias assessment. RESULTS: We selected 64 eligible studies, including 28 617 patients with NMIBC with available data on smoking status. In a meta-analysis of 28 studies with 7885 patients, we found that smokers (current/former) were at higher risk for recurrence (OR = 1.68; 95% CI 1.34-2.09; P < 0.0001) compared to never smokers. Subgroup analysis of 2967 patients revealed that current smokers were at a 1.24 higher risk of recurrence (OR = 1.24; 95% CI 1.02-1.50; P = 0.03) compared to former smokers. A meta-analysis of the hazard ratio revealed that smokers are at higher risk of recurrence (HR = 1.31; 95%CI 1.15-1.48; P < 0.0001) and progression (HR = 1.18; 95%CI 1.08-1.29; P < 0.001) compared to never smokers. Detrimental prognostic effect of smoking on progression, but not for recurrence risk was also noted in the subgroup analysis of high-risk patients (HR = 1.30; 95%CI 1.09-1.55; P = 0.004) and BCG-treated ones (HR = 1.15; 95%CI 1.06-1.25; P < 0.001). CONCLUSION: In conclusion, patients with non-muscle invasive bladder cancer and a history of smoking have a worse prognosis regarding recurrence-free and progression-free survival compared to non-smokers.

Radiation after radical prostatectomy in elderly patients - a SEER database-derived competing-risk survival analysis of propensity score-matched age groups.

Introduction: This study aimed to evaluate cancer-specific (CSM) and other-cause mortality (OCM) in elderly patients with prostate cancer treated with radical prostatectomy (RP) and postoperative radiotherapy (RT). Material and methods: The Surveillance, Epidemiology, and End Results (SEER) database was searched for clinically non-metastatic prostate cancer (PCa) treated with RT after RP between 2010 and 2015. Patients were stratified according to age groups and underwent propensity score (PS) matching. The Kaplan-Meier method and competing-risk Cox regression (CRR) were used for survival analysis. Results: In total, 5385 patients were analysed, including 738 (13.7%) elderly patients (≥70 years old) and 4647 (86.29%) younger individuals. A total of 54 (7.32%) and 69 (9.35%) patients aged ≥70 years died due to PCa and competing reasons, respectively. Among younger patients these included 275 (5.92%) and 208 (4.48%) deaths, respectively. At a median follow-up of 80 months, patients ≥70 years old had significantly shorter OCM (p <0.0001) than PS-matched younger controls without significant impairment of cancer-specific survival when compared to controls (p = 0.19). In CRR analysis older patients were at significantly higher risk of OCM (HR = 2.24, p = 0.0002 and HR = 3.3, p = 0.011 for patients aged ≥70 and ≥75 years, respectively). Simultaneously, the CRR revealed no increased risk of CSM for patients older than 70 and 75 years (HR = 1.2, p = 0.33 and HR = 1.53, p = 0.29, respectively). Conclusions: Elderly patients with PCa are at high risk of dying due to competing reasons, which might prevent the survival benefit of RT after RP. Selection for salvage and adjuvant RT in these individuals should be cautious.