The impact of metastasectomy on survival of patients with synchronous metastatic renal cell cancer in Finland: A nationwide study.

BACKGROUND AND OBJECTIVE: Most of the studies on metastasectomy in renal cell cancer are based on metachronous, often oligometastatic disease. Prior data on the impact of metastasectomy in synchronous metastatic renal cell cancer (mRCC) is, however, very scarce. We aimed to investigate the role of complete and incomplete metastasectomy in a large, nationwide patient population. METHODS: We analyzed nationwide data, including all synchronous mRCC cases in Finland diagnosed during a 6-year period identified from the Finnish Cancer Registry, and complemented with patient records from the treating hospitals. We only included the patients who underwent removal of the primary tumor by nephrectomy. We performed univariate and multivariable adjusted analysis to identify the effect of metastasectomy on overall survival (OS) and cancer-specific survival (CSS). RESULTS: We included 483 patients with synchronous mRCC. Overall, 57 patients underwent complete and 96 incomplete metastasectomy, while 330 patients had no metastasectomy. The median OS was 17.9 and CSS 17.2 months for all patients. The median OS and the median CSS were 59.3 and 60.8 months for the complete, 21.9 and 25.1 for the incomplete, and 14.5 and 14.8 months for the no metastasectomy groups (p < 0.001 for differences). In both applied multivariable statistical models, the OS and CSS benefit from complete metastasectomy remained significant (hazard ratios (HRs) varied between 0.42 and 0.54, p < 0.001) compared with the no metastasectomy group. However, there was no improvement in survival estimates in the incomplete metastasectomy group compared with the no metastasectomy group (HRs varied between 1.04 and 1.10, p > 0.40). CONCLUSIONS: Complete metastasectomy, when possible, can be considered as a treatment option for selected patients with synchronous mRCC who are fit for surgery. By contrast, we found no survival benefit from an incomplete metastasectomy suggesting that such procedures should not be performed for these patients.

Dampened Regulatory Circuitry of TEAD1/ITGA1/ITGA2 Promotes TGFß1 Signaling to Orchestrate Prostate Cancer Progression.

The extracellular matrix (ECM) undergoes substantial changes during prostate cancer (PCa) progression, thereby regulating PCa growth and invasion. Herein, a meta-analysis of multiple PCa cohorts is performed which revealed that downregulation or genomic loss of ITGA1 and ITGA2 integrin genes is associated with tumor progression and worse prognosis. Genomic deletion of both ITGA1 and ITGA2 activated epithelial-to-mesenchymal transition (EMT) in benign prostate epithelial cells, thereby enhancing their invasive potential in vitro and converting them into tumorigenic cells in vivo. Mechanistically, EMT is induced by enhanced secretion and autocrine activation of TGFß1 and nuclear targeting of YAP1. An unbiased genome-wide co-expression analysis of large PCa cohort datasets identified the transcription factor TEAD1 as a key regulator of ITGA1 and ITGA2 expression in PCa cells while TEAD1 loss phenocopied the dual loss of α1- and α2-integrins in vitro and in vivo. Remarkably, clinical data analysis revealed that TEAD1 downregulation or genomic loss is associated with aggressive PCa and together with low ITGA1 and ITGA2 expression synergistically impacted PCa prognosis and progression. This study thus demonstrated that loss of α1- and α2-integrins, either via deletion/inactivation of the ITGA1/ITGA2 locus or via loss of TEAD1, contributes to PCa progression by inducing TGFß1-driven EMT.

Nationwide analysis of survival after radical cystectomy for bladder cancer in Finland.

BACKGROUND: Population-based survival results after radical cystectomy (RC) are limited. Our objective was to report short and long-term survival results after RC for bladder cancer from Finland in a population-based setting. MATERIALS AND METHODS: The Finnish National Cystectomy Database containing retrospectively collected essential RC data covering the years 2005-2017 was combined with the survival data from the Finnish Cancer Registry. Kaplan-Meier plots were used to estimate survival and the survival graphs were illustrated according to the final pathological staging. Centers were divided according to operational volume, and the results were then compared using Pearsons's Chi-squared test. RESULTS: A total of 2047 patients were included in the study. 30-, and 90-day mortality was 1.3%, and 3.8%, respectively. The OS of the entire RC population at 5- and 10 years was 66% and 55%, and CSS was 74% and 72%, respectively. Center volume did not significantly associate with surgical mortality or long-term survival. The 5- and 10-year OS according to pT-category was 87% and 74% for pT0, 85% and 69% for pTa-pTis-pT1, 70% and 58% for pT2, 50% and 42% for pT3 and 41% and 30% for pT4. The corresponding 5- and 10-year CSS rates were 96% and 93% for pT0, 91% and 90% for pTa-pTis-pT1, 78% and 75% for pT2, 56% and 55% for pT3 and 47% and 44% for pT4. The 5- and 10-year OS rates in patients with no lymph node metastases (pN-) were 74% and 62%, and CSS 82% and 80%, respectively. If lymph nodes were positive (pN+), the corresponding OS rates were 44% and 34% and CSS 49% and 48%, respectively. CONCLUSION: RC survival results have improved in contemporary series and are associated with the pTNM-status. The nationwide results from Finland demonstrate outcome comparable to high volume single-center series.

Disassembly of α6ß4-mediated hemidesmosomal adhesions promotes tumorigenesis in PTEN-negative prostate cancer by targeting plectin to focal adhesions.

Loss of α6ß4-dependent hemidesmosomal adhesions has been observed during prostate cancer progression. However, the significance and underlying mechanisms by which aberrant hemidesmosome assembly may modulate tumorigenesis remain elusive. Using an extensive CRISPR/Cas9-mediated genetic engineering approaches in different prostate cancer cell lines combined with in vivo tumorigenesis studies in mice, bone marrow-on-chip assays and bioinformatics, as well as histological analysis of prostate cancer patient cohorts, we demonstrated that simultaneous loss of PTEN and hemidesmosomal adhesions induced several tumorigenic properties including proliferation, migration, resistance to anoikis, apoptosis, and drug treatment in vitro, and increased metastatic capacity in vivo. These effects were plectin-depended and plectin was associated with actin-rich adhesions upon hemidesmosome disruption in PTEN-negative prostate cancer cells leading to activation of EGFR/PI3K/Akt- and FAK/Src-pathways. These results suggest that analysis of PTEN and hemidesmosomal proteins may have diagnostic value helping to stratify prostate cancer patients with high risk for development of aggressive disease and highlight actin-associated plectin as a potential therapeutic target specifically in PTEN/hemidesmosome dual-negative prostate cancer.

Awareness of Smoking as a Risk Factor in Bladder Cancer: Results from the Prospective FinnBladder 9 Trial.

BACKGROUND: Data regarding patient education and smoking habits among bladder cancer patients are scarce. OBJECTIVE: To investigate awareness of smoking as a risk factor for bladder cancer among bladder cancer patients. DESIGN, SETTING, AND PARTICIPANTS: This is a substudy of a prospective, randomized, multicenter phase 3 trial (FinnBladder 9, NCT01675219). The data were collected at baseline and after 12 mo of follow-up between 2012 and 2020. INTERVENTION: Patients completed a comprehensive nonvalidated questionnaire on smoking in relation to bladder cancer. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcomes measured were patient-reported awareness of smoking as a risk factor for bladder cancer, and the effect of smoking on bladder cancer-related recurrence, progression, and death. Parametric data were compared using Student's t test and proportions using Fischer's exact test. Factors affecting baseline awareness of the effect of smoking cessation on bladder cancer were studied using logistic regression. RESULTS AND LIMITATIONS: Of the 411 patients randomized, 370 completed the baseline questionnaire and were included in the analysis. At baseline, 44% of patients were uncertain if smoking was a risk factor for bladder cancer. Patient awareness of the fact that smoking cessation reduces the risk of bladder cancer recurrence increased from 86% to 92% after 12 mo of follow-up (p = 0.038). Older patients and patients with recurrent bladder cancer had significantly less knowledge about the effect of smoking on bladder cancer recurrence, progression, and mortality. A major limitation is that the response rate was lower at the 12-mo follow-up visit than at baseline. CONCLUSIONS: Awareness of smoking as a bladder cancer risk factor is low. Older patients and patients with recurrent bladder cancer may need special attention regarding education. PATIENT SUMMARY: We looked at outcomes for smoking-related patient education on bladder cancer in a Finnish population. We conclude that older patients and patients with recurrent bladder cancer may need to be educated on this subject.

Transition to Targeted Therapies Improved the Prognosis and Increased the Utilization of Medical Treatments among Patients with Synchronous Metastatic Renal Cell Cancer.

Since the introduction of targeted therapies (TTs) for metastatic renal cell cancer (mRCC) in 2005, a limited amount of epidemiological data on efficacy of modern drug therapies for synchronous mRCC has been published. We present a comprehensive nationwide cohort including all cases of primarily metastasized renal cell cancer among adults diagnosed between 2005 and 2010, based on data from the Finnish Cancer Registry and patient records from treating hospitals. Applied treatment protocols and survival outcomes were analyzed. A total of 977 patients were included in the analysis; 499 patients were diagnosed between 2005 and 2007 and 478 patients were diagnosed between 2008 and 2010. The median overall survival (OS) was 8.80 months (95% confidence interval (CI): 7.60-10.02). The median OS of the patients diagnosed at the latter era was significantly better (11.1; 95% CI: 8.8-13.4 vs. 7.0; 95% CI: 5.7-8.3 months, p ≤ 0.001). A total number of 524 (53.8%) patients received drug therapy. Altogether, TTs including tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors (mTORi), and vascular endothelial growth factor inhibitor covered 331 (63.2%) of first-line treatments, whereas interferon and its combinations with chemotherapy were used for 186 (35.5%) patients. The median OS rates for TT and interferon as first-line therapy groups were 19.9 (16.9-22.8) and 14.9 (12.3-17.4) months, respectively. The OS for patients who did not receive drug therapy after cytoreductive nephrectomy was dismal. We found that the OS estimate of mRCC patients in Finland has improved since the introduction of tyrosine kinase inhibitors. However, the prognosis remains poor for frail, elderly patients with an impaired performance status.

Nephrectomy improves the survival of metastatic renal cell cancer patients with moderate to good performance status-results from a Finnish nation-wide population-based study from 2005 to 2010.

BACKGROUND: The purpose of this study was to evaluate the effects of cytoreductive nephrectomy (CN) and metastasectomies on the survival of patients with synchronous metastatic renal cell cancer (mRCC) using real-life, population-based national dataset. METHODS: Nationwide data, including all cases of synchronous mRCC in Finland diagnosed on a 6-year timeframe, based on the Finnish Cancer Registry and complemented with patient records from the treating hospitals, were analyzed. Patients with Eastern Cooperative Oncology Group (ECOG) performance status 3-4 were excluded. Univariate and adjusted multivariable survival analysis were performed, including subgroup analysis for patients with different medical therapies. Nephrectomy complications were also analyzed. RESULTS: A total of 732 patients were included in the analysis. CN was performed for 389 (53.1%) patients, whereas 68 (9.3%) patients underwent nephrectomy and metastasectomies of all lesions (surgery with curative intent). Median overall survival (OS) for patients who did not undergo nephrectomy was 5.9 (95% confidence interval [CI] = 4.6-7.2) months. Patients who had a CN had a median OS of 16.6 (95% CI = 14.2-19.1, p < 0.001) months, whereas patients who had surgery with curative intent had a median OS of 51.3 (95% CI = 36.0-66.6, p < 0.001) months. The survival benefit of CN and metastasectomies remained significant in all medical therapy subgroups and in both of the applied multivariable statistical models. CONCLUSIONS: Surgical treatment of metastatic renal cell cancer is associated with a significant survival benefit in patients with good and moderate performance status, regardless of the chosen medical therapy.

Keyhole versus Sugarbaker techniques in parastomal hernia repair following ileal conduit urinary diversion: a retrospective nationwide cohort study.

BACKGROUND: Previous research on parastomal hernia repair following ileal conduit urinary diversion is limited. This nationwide cohort study aims to present the results of keyhole and Sugarbaker techniques in parastomal hernia repair in the setting of ileal conduit urinary diversion. METHOD: All patients in this cohort underwent primary elective parastomal hernia repair following ileal conduit urinary diversion in four university hospitals and one central hospital in Finland in 2007-2017. Retrospective clinical data were collected from patient registries to compare keyhole and Sugarbaker parastomal hernia repair techniques. The primary outcome was parastomal hernia recurrence during the follow-up from primary surgery to the last confirmed follow-up date of the patient. The secondary outcomes were reoperations during the follow-up and complication rate at 30 days' follow-up. RESULTS: The results of 28 hernioplasties were evaluated. The overall parastomal hernia recurrence rate was 18%, the re-operation rate was 14%, and the complication rate was 14% during the median follow-up time of 30 (21-64) months. Recurrence rates were 22% (4/18) after keyhole repair and 10% (1/10) after Sugarbaker repair. Re-operation rates referred to keyhole repair were 22% and Sugarbaker repair 0% during follow-up. The majority of reoperations were indicated by recurrence. Complication rates were 17% after keyhole and 10% after Sugarbaker repair during the 30 days' follow-up. CONCLUSION: The results of parastomal hernia repair in the setting of ileal conduits are below optimal in this nationwide cohort comparing keyhole to Sugarbaker repair in elective parastomal hernia repair. Nonetheless, the Sugarbaker technique should be further studied to confirm the encouraging results of this cohort in terms of recurrence.

Symptoms and diagnostic delays in bladder cancer with high risk of recurrence: results from a prospective FinnBladder 9 trial.

PURPOSE: To investigate the symptoms and delays in the clinical pathway of bladder cancer (BC). METHODS: This is a substudy of a prospective, randomized, multicenter phase III study (FinnBladder 9, NCT01675219) where the efficacy of photodynamic diagnosis and 6 weekly optimized mitomycin C instillations are studied in pTa bladder cancer with high risk for recurrence. The data of presenting symptoms and critical time points were prospectively collected, and the effect of factors on delays was analyzed. RESULTS: At the time of analysis, 245 patients were randomized. Analysis included 131 patients with primary bladder cancer and their complete data. Sixty-nine percent had smoking history and 67% presented with macroscopic hematuria. Median patient delay (from symptoms to health-care contact) was 7 days. The median general practice delay (from health-care contact to urology referral) was 8 days. Median time from urology referral to cystoscopy was 23 days and from cystoscopy to TUR-BT 21 days. Total time used in the clinical pathway (from symptom to TUR-BT) was 78 days. Current and former smokers had non-significantly shorter patient-related and general practice delays compared to never smokers. TUR-BT delay was significantly shorter in patients with malignant cytology (16 days) compared to patients with benign cytology (21 days, p = 0.03). CONCLUSIONS: Patient-derived delay was short and most of the delay occurred in the referral centers. The majority had macroscopic hematuria as the initial symptom. Surprisingly, current and past smokers were more prone to contact the health-care system compared to never smokers.

Multiparametric MRI prior to radical prostatectomy identifies intraductal and cribriform growth patterns in prostate cancer.

OBJECTIVES: To evaluate the diagnostic value of multiparametric prostate magnetic resonance imaging (mpMRI) prior to radical prostatectomy with curative intent for the detection of cribriform architecture (CA) and intraductal prostate cancer (IDC), which have recently been demonstrated to be adverse pathological features. PATIENTS AND METHODS: The study included 124 men who underwent mpMRI prior to radical prostatectomy at our centre. Preoperative mpMRI, prostatectomy histology and clinical follow-up details were reviewed retrospectively. The diagnostic value of mpMRI was evaluated on the basis of the detection rate. Secondly, the prognostic significance of CA/IDC among grade group (GG)2 cancers with regard to biochemical recurrence (BCR)-free survival was assessed using Kaplan-Meier analysis, with the log rank test and Fisher's exact test. RESULTS: Pathological examination of radical prostatectomy specimens identified CA/IDC in 89 of 124 cases (71%) and mpMRI identified 86/95 of tumours including any CA/IDC with a sensitivity of 90.5% (95% confidence interval 82.8-95.6%). When localization of the lesions was compared, there was an association between the highest Prostate Imaging-Reporting and Data System classification and the highest pathological grade in 106 of the 124 cases (85.5%). In patients with GG2 lesions, BCR occurred in 11 of 31 (35.5%) with CA/IDC and two of 21 (9.5%) without CA/IDC (P = 0.034). CONCLUSION: Multiparametric MRI has good sensitivity for detection of pathological primary prostate cancer, including most cases with CA/IDC; however, reliable prediction of GG2 tumours with CA/IDC for individual risk stratification remains challenging.

Biology and Clinical Implications of the 19q13 Aggressive Prostate Cancer Susceptibility Locus.

Genome-wide association studies (GWAS) have identified rs11672691 at 19q13 associated with aggressive prostate cancer (PCa). Here, we independently confirmed the finding in a cohort of 2,738 PCa patients and discovered the biological mechanism underlying this association. We found an association of the aggressive PCa-associated allele G of rs11672691 with elevated transcript levels of two biologically plausible candidate genes, PCAT19 and CEACAM21, implicated in PCa cell growth and tumor progression. Mechanistically, rs11672691 resides in an enhancer element and alters the binding site of HOXA2, a novel oncogenic transcription factor with prognostic potential in PCa. Remarkably, CRISPR/Cas9-mediated single-nucleotide editing showed the direct effect of rs11672691 on PCAT19 and CEACAM21 expression and PCa cellular aggressive phenotype. Clinical data demonstrated synergistic effects of rs11672691 genotype and PCAT19/CEACAM21 gene expression on PCa prognosis. These results provide a plausible mechanism for rs11672691 associated with aggressive PCa and thus lay the ground work for translating this finding to the clinic.

MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis.

BACKGROUND: Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography-guided biopsy for prostate-cancer detection in men with a raised prostate-specific antigen level who have not undergone biopsy. However, comparative evidence is limited. METHODS: In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography-guided biopsy. Men in the MRI-targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10-to-12-core, transrectal ultrasonography-guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. RESULTS: A total of 500 men underwent randomization. In the MRI-targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI-targeted biopsy group, as compared with 64 of 248 (26%) in the standard-biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI-targeted biopsy group than in the standard-biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, -13 percentage points; 95% CI, -19 to -7; P<0.001). CONCLUSIONS: The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027 .).

Lesion size on prostate magnetic resonance imaging predicts adverse radical prostatectomy pathology.

OBJECTIVES: To investigate the value of the maximal lesion diameter on preoperative multiparametric/bi-parametric magnetic resonance imaging for estimating the risk of adverse radical prostatectomy pathology. PATIENTS AND METHODS: Consecutive patients (n = 162) with prostate multiparametric or biparametric magnetic resonance images acquired before prostatectomy were retrospectively stratified into two groups: 65 patients with normal MRI (n = 18) or a suspicious lesion <15 mm in diameter (n = 47), and 97 patients with a lesion diameter ≥15 mm. The presence of extraprostatic extension, margin positivity, seminal vesicle invasion, and lymph node metastasis was examined in these groups using logistic regression analysis, including preoperative clinical parameters (prostate-specific antigen concentration, biopsy Gleason grade group, clinical T-stage, and D'Amico risk group). RESULTS: The prevalence of extraprostatic extension, margin positivity, and seminal vesicle invasion was 53.1% (86/162), 22.8% (37/162), and 17.9% (29/162), respectively. Lymphadenectomy was performed in 64 men, of whom 14 had lymph node metastasis. Lesion diameter ≥15 mm strongly predicted extraprostatic extension (Odds ratio: 7.94, 95% confidence interval: 3.87-16.28, p < 0.001), margin positivity (Odds ratio: 7.86, 95% confidence interval 2.63-23.51, p < 0.001), and seminal vesicle invasion (Odds ratio: 7.57, 95% confidence interval 2.18-26.22, p = 0.001). Lesion diameter ≥15 mm was an independent risk factor for adverse prostatectomy pathology. Lesion diameter ≥20 mm, but not ≥15 mm, was a significant risk factor for lymph node metastasis. CONCLUSION: Magnetic resonance imaging lesion diameter ≥15 mm is an independent risk factor for extraprostatic extension, margin positivity and seminal vesicle invasion.

Urinary Sample Collection Methods in Ileal Conduit Urinary Diversion Patients: A Randomized Control Trial.

PURPOSE: The purpose of this study was to compare bacteriological urinalysis findings using 3 urinary sample collection methods (clean stoma catheterization, urine dripping from the stoma, urine collected from the clean urostomy pouch) in ileal conduit urinary diversion patients. DESIGN: Randomized controlled trial. SAMPLE AND SETTING: Twenty-seven patients with ileal conduit urinary diversion from an outpatient urology clinic were enrolled; 9 patients were seen twice, for a total of 36 subjects and comparisons. METHODS: Data were collected during a clinic visit by a trained research nurse. Patients were randomized into 2 groups: group A had the first urine sample collected by clean stoma catheterization, followed by sample collection by urine dripping from the stoma; group B had the first urine sample collection by urine dripping from the stoma, followed by sample collected by clean stoma catheterization. All patients had a third urine sample collected from a factory-clean urostomy pouch. Bacteriological urinalysis findings were compared among methods. Descriptive analyses were summarized using mean, percentage, and frequency. The mean ages of the patients between the groups were compared with the t test. Other between-group comparisons were performed using the Fisher exact test. Urinary culture finding differences among the same patients were evaluated using the McNemar test. Sensitivity and specificity of the different urine sample collection methods were calculated assuming urine sample collection by catheterization as a reference method. RESULTS: Uropathogen bacteria were detected in urinary culture in 16 of 36 samples (44%) collected by clean stoma catheterization, 15 of 36 samples (42%) collected by urine dripping directly from the stoma, and 13 of 35 samples (37%) collected from the clean urostomy pouch. Significant differences among the urine collection methods were not detected. Assuming catheterization as the most reliable method of sample collection, the sensitivity and specificity of the urine dripping from stoma collection method were 81.3% and 90.0%, respectively. The sensitivity and specificity of the urostomy pouch collection method were 73.3% and 90.0%, respectively. Among the same patients, there were no significant differences in the incidence of uropathogen bacteria when clean stoma catheterization was compared with urine dripping from the stoma and urostomy pouch methods. CONCLUSION: This study provides clinically relevant information regarding urine collection methods in ileal conduit patients. Urinary sample collection by urine dripping directly from the stoma or collected from a clean urostomy pouch provided similar uropathogen bacteria findings compared with sample collection by clean stoma catheterization.

Neoadjuvant Chemotherapy Does Not Increase the Morbidity of Radical Cystectomy: A 10-year Retrospective Nationwide Study.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is underutilized in the treatment of bladder cancer (BC). OBJECTIVE: To investigate the effect of NAC on the risk of surgical complications for radical cystectomy (RC) in a population-based setting. DESIGN, SETTING, AND PARTICIPANTS: All radical cystectomies performed in Finland during 2005-2014 were included in the study. Data were collected retrospectively using a web-based data collection platform. Complications were recorded for 90 d using the Clavien classification. Patients treated with NAC were compared to patients receiving RC alone using three cohorts and approaches: the entire cohort, a neoadjuvant period cohort, and a matched cohort. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: For all three cohorts, odds ratios (ORs) were estimated using simple binary logistic regression. In addition, a multivariable stratified logistic model with propensity score was used. For the matched cohort analysis, both univariate and adjusted analyses were carried out. RESULTS AND LIMITATIONS: During 2005-2014, 1427 RCs were performed in Finland, of which 1385 were included in the analyses. NAC was introduced in 2008, and 231 patients (16%) were assigned to NAC and 214 (15%) received two or more cycles of chemotherapy. Within 90 d, 61% of patients experienced complications and mortality was 4% (1.9% in the NAC group, and 4.4% in the RC-alone group). In simple binary logistic regression, NAC patients had significantly fewer complications, but this was not observed in multivariable or propensity score analyses. In the matched cohort analyses, no differences in complication rates could be observed. None of the analyses demonstrated higher complication rates in the NAC group. CONCLUSIONS: Our retrospective study reports on nationwide use of NAC for BC and demonstrates that NAC does not increase RC morbidity. PATIENT SUMMARY: Chemotherapy given before radical surgery does not increase severe postoperative complications in the treatment of bladder cancer.

External beam radiation for the treatment of castration-resistant prostate cancer following primary hormonal therapy with androgen ablation: Analysis and outcome of 21 patients.

Patients who undergo early androgen-deprivation therapy for prostate cancer may eventually develop castration-resistant prostate cancer. However, no optimal treatment for non-metastasized castration-resistant prostate cancer has yet been established. In the present retrospective, single-institutional study, the radiotherapy (RT) outcomes were evaluated in patients who underwent androgen-deprivation therapy for non-metastatic prostate cancer and subsequently developed castration-resistant disease. Following a thorough chart review, the data of 21 patients with castration-resistant prostate cancer who were treated between 2000 and 2010 with external beam radiation therapy (EBRT) at a prostate radiation dose of >45 Gy were evaluated. Of the 21 patients, 16 (76%) developed biochemical recurrence after RT, with a mean time to biochemical recurrence of 17 months. A total of 18 patients succumbed to the disease during follow-up, with a mean survival of 3 years after RT. A radiation dose of >66 Gy was associated with a longer time to biochemical recurrence after RT (P=0.011) and a longer survival, compared with a dose of ≤66 Gy (P=0.028). The mean overall survival time after RT was 42 months and did not depend on the primary hormonal treatment. Prostate-specific survival time was negatively associated with the Gleason score at diagnosis. The prostate-specific antigen (PSA) concentration prior to RT was a prognostic factor for biochemical recurrence of prostate cancer after RT, as well as for prostate cancer-specific survival. Finally, the multivariate analysis revealed that age, PSA concentration prior to RT and a high Gleason score were independent prognostic factors for prostate cancer-specific survival. Overall, our study findings demonstrated that disease progression was common after EBRT for castration-resistant prostate cancer and that survival was limited. However, young patients and those with low-risk disease at the time of diagnosis may benefit from RT.

Prostate-specific antigen nadir concentration, hypertension and diabetes as risk factors for biochemical failure after permanent 125I seed brachytherapy for prostate cancer.

The aim of this study was to evaluate risk factors for biochemical failure (BF) following permanent prostate seed 125I brachytherapy for prostate cancer. The study reviewed the medical records of 607 patients with biopsy-proven prostate adenocarcinoma who were treated at Oulu University Hospital between 2001 and 2014. Clinical characteristics at diagnosis, treatment-related data and follow-up data were collected to identify potential risk factors for BF, which was defined using the Phoenix criteria [prostate-specific antigen (PSA) increase >2 µg/l from the PSA nadir concentration, which defined as the lowest PSA concentration observed after BT]. The median follow-up was 81 months. BF was detected in 117 (19.3%) patients. The PSA nadir concentration was associated with BF. The mean times to BF were 114 [95% confidence interval (CI): 112-116] and 55 (95% CI: 47-63) months for patients with PSA nadir concentrations <0.5 and ≥0.5 µg/l, respectively (P<0.001). Patients with underlying hypertension or diabetes tended to develop BF more rapidly. For patients without and with hypertension, the mean times to BF were 104 (95% CI: 100-107) and 98 (95% CI: 93-103) months, respectively (P=0.035). For patients without and with diabetes, the mean times to BF were 103 (95% CI: 100-106) and 89 (95% CI: 77-102) months, respectively (P=0.006). The overall survival and prostate cancer-specific survival rates were 90.3 and 98.0%, respectively. The mean overall survival and prostate-cancer specific survival times were 147 and 158 months, respectively. Therefore, PSA nadir level was identified as a clear risk factor for BF. In addition, BF tended to develop more rapidly among patients with underlying hypertension or diabetes. These risk factors should be considered, and individually tailored follow-up may be useful for identifying patients requiring more intense follow-up for early BF detection.

Prostate cancer incidence in men with self-reported prostatitis after 15 years of follow-up.

Controversy exists regarding a possible association between prostatitis and prostate cancer. To further evaluate the incidence of prostate cancer following prostatitis, a study of prostate cancer incidence in a cohort of Finnish men was performed. The original survey evaluating self-reported prostatitis was conducted in 1996-1997. A database review was conducted focusing on prostate cancer diagnoses in the cohort. In 2012, there were 13 (5.2%) and 27 (1.8%) prostate cancer cases among men with (n=251) and without (n=1,521) prostatitis symptoms, respectively. There were no significant differences in age, primary therapy distribution, prostate-specific antigen levels, Gleason score, clinical T-class at the time of prostate cancer diagnosis, or time lag between the original survey and prostate cancer diagnosis. The standardized incidence ratio (SIR) of prostate cancer was 1.16 [95% confidence interval (CI), 0.62-1.99] and 0.44 (95% CI, 0.29-0.64) among men with and without prostatitis symptoms, respectively. After 15 years of follow-up subsequent to self-reported prostatitis, no evident increase in incidence of prostate cancer was detected among Finnish men with prostatitis symptoms. The higher percentage of prostate cancer among men with prostatitis symptoms appears to be due to coincidentally low SIR of prostate cancer among men without prostatitis symptoms, and may additionally be due to increased diagnostic examinations. Further research is required to confirm this speculation.

Prebiopsy Multiparametric Magnetic Resonance Imaging for Prostate Cancer Diagnosis in Biopsy-naive Men with Suspected Prostate Cancer Based on Elevated Prostate-specific Antigen Values: Results from a Randomized Prospective Blinded Controlled Trial.

BACKGROUND: Multiparametric magnetic resonance imaging (MP-MRI) may improve the detection of clinically significant prostate cancer (PCa). OBJECTIVE: To compare MP-MRI transrectal ultrasound (TRUS)-fusion targeted biopsy with routine TRUS-guided random biopsy for overall and clinically significant PCa detection among patients with suspected PCa based on prostate-specific antigen (PSA) values. DESIGN, SETTING, AND PARTICIPANTS: This institutional review board-approved, single-center, prospective, randomized controlled trial (April 2011 to December 2014) included 130 biopsy-naive patients referred for prostate biopsy based on PSA values (PSA <20 ng/ml or free-to-total PSA ratio ≤0.15 and PSA <10 ng/ml). Patients were randomized 1:1 to the MP-MRI or control group. Patients in the MP-MRI group underwent prebiopsy MP-MRI followed by 10- to 12-core TRUS-guided random biopsy and cognitive MRI/TRUS fusion targeted biopsy. The control group underwent TRUS-guided random biopsy alone. INTERVENTION: MP-MRI 3-T phased-array surface coil. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the number of patients with biopsy-proven PCa in the MP-MRI and control groups. Secondary outcome measures included the number of positive prostate biopsies and the proportion of clinically significant PCa in the MP-MRI and control groups. Between-group analyses were performed. RESULTS AND LIMITATIONS: Overall, 53 and 60 patients were evaluable in the MP-MRI and control groups, respectively. The overall PCa detection rate and the clinically significant cancer detection rate were similar between the MP-MRI and control groups, respectively (64% [34 of 53] vs 57% [34 of 60]; 7.5% difference [95% confidence interval (CI), -10 to 25], p=0.5, and 55% [29 of 53] vs 45% [27 of 60]; 9.7% difference [95% CI, -8.5 to 27], p=0.8). The PCa detection rate was higher than assumed during the planning of this single-center trial. CONCLUSIONS: MP-MRI/TRUS-fusion targeted biopsy did not improve PCa detection rate compared with TRUS-guided biopsy alone in patients with suspected PCa based on PSA values. PATIENT SUMMARY: In this randomized clinical trial, additional prostate magnetic resonance imaging (MRI) before prostate biopsy appeared to offer similar diagnostic accuracy compared with routine transrectal ultrasound-guided random biopsy in the diagnosis of prostate cancer. Similar numbers of cancers were detected with and without MRI. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01357512.

Treatment of renal angiomyolipoma: pooled analysis of individual patient data.

BACKGROUND: This study was performed to evaluate the impact of baseline characteristics and treatment methods on the outcome of sporadic renal angiomyolipoma (AML). METHODS: This was a pooled analysis of individual data of 441 patients with AML retrieved from 58 studies and 3 institutional series. RESULTS: Ninety-three patients underwent nephrectomy, 163 partial nephrectomy/enucleation, 128 embolisation, 19 cryoablation, 6 radiofrequency ablation, and 32 conservative treatment. Their mean follow-up period was 44.5 months. Patients who experienced major bleeding at presentation had significantly larger tumours than did those without bleeding (mean diameter, 10.1 vs. 5.9 cm, respectively; p < 0.0001). A total of 9.4 % and 26.4 % of bleeding tumours had a diameter of <4 and <6 cm, respectively. A tumour diameter of ≥8.0 cm (hazard ratio, 2.07; 95 % confidence interval, 1.20-4.77) and the treatment method (p = 0.001) were independent predictors of re-intervention. The risk of re-intervention was significantly higher after embolisation, particularly for large tumours (5-year rate of freedom from re-intervention: diameter of ≥8.0 cm, 49.2 %; diameter of <8.0 cm, 74.8 %; p = 0.018). Conservatively treated AMLs had a mean baseline diameter of 3.2 ± 2.7 cm; after 41 months, their mean diameter was 3.7 ± 3.1 cm (p = 0.109). CONCLUSIONS: The prevalence of major bleeding is high in sporadic AMLs with a diameter of >6 cm. These results suggest that conservative treatment can be considered in AMLs of <6 cm in diameter. Among current treatment methods, embolisation was associated with a significantly higher risk of re-intervention. Further studies are needed to define risk factors for bleeding and assess the relative benefits of different treatment modalities.