Applications of artificial intelligence in urologic oncology.

PURPOSE: With the recent rising interest in artificial intelligence (AI) in medicine, many studies have explored the potential and usefulness of AI in urological diseases. This study aimed to comprehensively review recent applications of AI in urologic oncology. MATERIALS AND METHODS: We searched the PubMed-MEDLINE databases for articles in English on machine learning (ML) and deep learning (DL) models related to general surgery and prostate, bladder, and kidney cancer. The search terms were a combination of keywords, including both "urology" and "artificial intelligence" with one of the following: "machine learning," "deep learning," "neural network," "renal cell carcinoma," "kidney cancer," "urothelial carcinoma," "bladder cancer," "prostate cancer," and "robotic surgery." RESULTS: A total of 58 articles were included. The studies on prostate cancer were related to grade prediction, improved diagnosis, and predicting outcomes and recurrence. The studies on bladder cancer mainly used radiomics to identify aggressive tumors and predict treatment outcomes, recurrence, and survival rates. Most studies on the application of ML and DL in kidney cancer were focused on the differentiation of benign and malignant tumors as well as prediction of their grade and subtype. Most studies suggested that methods using AI may be better than or similar to existing traditional methods. CONCLUSIONS: AI technology is actively being investigated in the field of urological cancers as a tool for diagnosis, prediction of prognosis, and decision-making and is expected to be applied in additional clinical areas soon. Despite technological, legal, and ethical concerns, AI will change the landscape of urological cancer management.

Benign Prostatic Hyperplasia and the Risk of Falls in Older Men: Insights From a Population-Based Study on Geriatric Morbid Conditions.

PURPOSE: The purpose of this study was to explore the association between benign prostatic hyperplasia (BPH) and the incidence of falls from the perspective of geriatric morbid conditions. METHODS: Data were sourced from the triennial National Survey of Older Koreans conducted by the Ministry of Health and Welfare (2017-2020). In total, 8,135 male participants aged 65 and older were included, and information was gathered through questionnaires and physical measurements. Logistic regression analysis was utilized to determine the impact of BPH on the risk of falls, and subgroup analyses were conducted to examine the influence of BPH on specific types of falls. RESULTS: Of the participants, 15.2% (1,238 of 8,135) reported that their BPH treatment exceeded 3 months, and 8.0% (648 of 8,135) reported experiencing falls, with 61.4% (398/648) of these falls resulting in injuries. A significant association was identified between BPH and both falls (odds ratio [OR], 1.798; 95% confidence interval [CI], 1.479-2.185) and falls with injuries (OR, 2.133; 95% CI, 1.689-2.694). A subgroup analysis indicated a correlation between BPH and falls in groups having one (OR, 1.912; 95% CI, 1.356-2.694) and 2 or more conditions (OR, 1.856; 95% CI, 1.455-2.367) involving visual and auditory impairments, cognitive decline, depression, lower motor weakness, and limitations in daily activities. CONCLUSION: The findings indicate that BPH contributes to the incidence of falls among older men, particularly those with comorbid conditions. Considering the heightened fall risk among elderly individuals suffering from multiple morbidities, particularly those with BPH, targeted interventions are essential for mitigating the risk of falls in this vulnerable group.

Deep Learning Model for Real­time Semantic Segmentation During Intraoperative Robotic Prostatectomy.

Background and objective: Recently, deep learning algorithms, including convolutional neural networks (CNNs), have shown remarkable progress in medical imaging analysis. Semantic segmentation, which segments an unknown image into different parts and objects, has potential applications in robotic surgery in areas where artificial intelligence (AI) can be applied, such as in AI-assisted surgery, surgeon training, and skill assessment. We aimed to investigate the performance of a CNN-based deep learning model in real-time segmentation in robot-assisted radical prostatectomy (RALP). Methods: Intraoperative videos of RALP procedures were obtained. The reinforcement U-Net model was used for segmentation. Segmentation of the images of instruments, bladder, prostate, and seminal vesicle-vas deferens was performed. The dataset was preprocessed and split randomly into training, validation, and test data in a 7:2:1 ratio. Dice coefficient, intersection over union (IoU), and accuracy by class, which are commonly used in medical image segmentation, were calculated to evaluate the performance of the model. Key findings and limitations: From 120 patient videos, 2400 images were selected for RALP procedures. The mean Dice scores for the identification of the instruments, bladder, prostate, and seminal vesicle-vas deferens were 0.96, 0.74, 0.85, and 0.84, respectively. Overall, when applied to the test data, the model had a mean Dice coefficient value of 0.85, IoU of 0.77, and accuracy of 0.85. Limitations included the sample size, lack of diversity in the methods of surgery, incomplete surgical processes, and lack of external validation. Conclusions and clinical implications: The CNN-based segmentation provides accurate real-time recognition of surgical instruments and anatomy in RALP. Deep learning algorithms can be used to identify anatomy within the surgical field and could potentially be used to provide real-time guidance in robotic surgery. Patient summary: We demonstrate the potential effectiveness of deep learning segmentation in robotic prostatectomy procedures. Deep learning algorithms could be used to identify anatomical structures within the surgical field and may provide real-time guidance in robotic surgery.

The association between testosterone deficiency and nocturia: Insights from The National Health and Nutrition Examination Survey data set.

AIMS: To examine the association between testosterone deficiency (TD) and nocturia in males, with specific attention to age and cardiovascular disease (CVD) comorbidity. METHODS: This cross-sectional study utilized the National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2016, assessing 6137 adult male participants. TD was defined by a serum total testosterone (TT) concentration less than 300 ng/dL. Nocturia was determined based on participants' responses to a standard NHANES question regarding the frequency of urination during the night. RESULTS: The study observed a significant association between TD and nocturia (adjusted odds ratio [95% confidence interval] = 1.211 [1.060-1.384], p = 0.005). Moreover, a U-shape pattern was noted in the relationship between serum TT concentration and the relative odds of nocturia. Subgroup analysis revealed a robust correlation between TD and nocturia in those over 60 years old, and those with hypertension, dyslipidemia, and CVDs. CONCLUSION: Our findings suggest a positive correlation between TD and nocturia, particularly among elderly individuals with CVD. This association underscores the potential therapeutic significance of addressing TD in the management of nocturia. Furthermore, longitudinal studies are needed to establish a causal relationship between TD and nocturia.

Predictive factors for postoperative medication therapy for overactive bladder symptoms after holmium laser enucleation of prostate.

OBJECTIVE: To preoperative factors that could predict the persisting storage symptoms after Holmium laser enucleation of the prostate (HoLEP). METHODS: Medical records of 257 patients who underwent HoLEP between December 2014 and January 2021 were reviewed. Participants with a follow-up period exceeding 6 months were included. Preoperative data, including International Prostate Symptom Score (IPSS), uroflowmetry, prostate size, and prostate-specific antigen, were collected. All participants underwent a preoperative urodynamic study. The correlation between perioperative variables and postoperative medication therapy (antimuscarinics or beta-3 agonists) was assessed. RESULTS: Out of 257 participants in the study, 46 (18.6%) were allocated to the medication group, of which 25 (54.3%) initiated medication therapy postoperatively. The medication group showed worse postoperative IPSS storage symptom score and quality of life score compared to the medication-free group (p = 0.048 and p = 0.002, respectively), but no significant differences were observed in complications or operative variables. In the de-novo medication group, patients had lower preoperative Qmax , larger prostate volume, and smaller maximum cystometric capacity (MCC) compared to the persisting medication group (p = 0.020, p = 0.009, and p = 0.008, respectively). Overactive bladder (OAB) history, terminal detrusor overactivity (DO), and IPSS urgency item were identified as possible predictive factors for post-HoLEP medication use. CONCLUSIONS: Preoperative factors such as OAB history, terminal DO, and IPSS urgency item may predict the need for post-HoLEP medication therapy. Further follow-up studies are warranted to understand the characteristics of the de-novo medication group due to the significant discomfort it can cause to patients.

Glucocorticoid receptor and androgen receptor-targeting therapy in patients with castration-resistant prostate cancer.

Objective: The glucocorticoid receptor (GR) promotes resistance to androgen receptor (AR)-targeting therapies in castration-resistant prostate cancer (CRPC) by bypassing AR blockade. However, the clinical relevance of evaluating GR expression in patients with CRPC has not been determined. The present study investigated the association of relative GR expression in CRPC tissue samples with treatment response to AR-targeting therapy. Methods: Levels of GR, AR-FL, and AR-V7 mRNAs were measured in prostate cancer tissue from prospectively enrolled CRPC patients who were starting treatment. Patients were divided into groups with high and low AR-V7/AR-FL ratios and with high and low GR/AR-FL ratios. The primary endpoint was prostate-specific antigen (PSA) response rate to treatment. Results: Evaluation of 38 patients treated with AR-targeting therapies showed that the PSA response rate was significantly higher in patients with low than high AR-V7/AR-FL ratios (77.8% vs. 25.0%, p=0.003) and in patients with low than high GR/AR-FL ratios (81.3% vs. 27.3%, p=0.003). Patients with low GR/AR-FL ratios had higher rates of PSA progression-free survival (46.0% vs. 22.4%, p=0.006), radiologic progression-free survival (28.9% vs. 10.0%, p=0.02), and overall survival (75.2% vs. 48.0%, p=0.037) than patients with high GR/AR-FL ratios. The association of GR/AR-FL ratio with PSA response to AR-targeting therapy remained significant in multivariable models. Evaluation of the 14 patients who received taxane chemotherapy showed that PSA response rates did not differ significantly in those with low and high AR-V7/AR-FL and GR/AR-FL ratios, although no definitive conclusions can be drawn due to the small number of patients. Conclusion: Relative GR expression is associated with sensitivity to AR-targeting therapy and survival in patients with CRPC. Large-scale prospective validation and liquid biopsy-based studies are warranted.

Predictive factors for alpha blocker use after transurethral prostatectomy: Can preoperative urodynamic outcome predict alpha blocker medication after surgery?

OBJECTIVE: To analyze the diagnostic value of conducting urodynamic study (UDS) and show predictors for alpha blocker use 12 months after transurethral prostatectomy. MATERIALS AND METHODS: Our study includes 406 participants that had a transurethral prostatectomy at our hospital between 2010 and 2019. All participants took alpha blockers for more than a month. We collected the participants' preoperative international prostatic symptom score (IPSS), uroflowmetry, transrectal ultrasound, and serum prostatic antigen (PSA) level. A total of 254 patients conducted UDS. After surgery, participants visited our hospital at 1,3,6, and 12 months. RESULTS: 133 patients (32.6%) took alpha blockers continuously for 12 months after surgery. They reported poor preoperative IPSS scores and uroflowmetry outcomes. They also had high postoperative PVR (40.68±24.56 vs 29.34±25.11, p<0.001) and total IPSS score (10.35±7.96 vs 8.43±6.74, p = 0.018) compared to the group which discontinued alpha blockers. A multivariate analysis (Table 2) found that conducting preoperative UDS (Odds ratio (OR) 6.067, p<0.001) Age>75 (OR 2.463, p<0.001), a history of taking 5-alpha reductase inhibitors (5-ARI) before surgery (OR 2.186 [95% CI 1.334-3.583], p = 0.002), IPSS item straining (OR 1.224, p = 0.003), duration of taking alpha blockers [OR 1.009, p = 0.020), and Qmax (OR 0.926, p = 0.018), PVR (OR 1.002, p = 0.022) were confirmed as a strong predictors of persistent alpha blocker use. CONCLUSION: Conducting preoperative UDS, Age>75, history of taking 5-ARI before surgery, IPSS item straining, duration of alpha blocker medication, Qmax, and PVR are possible determinant factors of alpha blocker use after surgery. By comparing UDS outcomes, detrusor underactivity can be a strong predictor of persisting alpha blocker therapy 12 months after surgery.

The Relationship Between Nocturia and Mortality: Data From the National Health and Nutrition Examination Survey.

PURPOSE: We investigated the relationship between nocturia and mortality risk in the United States. METHODS: Data were obtained from the National Health and Nutrition Examination Survey 2005-2010. Mortality data were obtained by linking the primary database to death certificate data found in the National Death Index with mortality follow-up up to December 31, 2015. Nocturia was defined based on symptoms reported in the symptom questionnaire. We categorized patients into 2 groups: mild nocturia (2-3 voids/night) and moderate-to severe nocturia (≥4 voids/night). Multiple Cox regression analyses were performed with adjustment for confounding variables at the baseline survey. RESULTS: This study included 9,892 adults (4,758 men, 5,134 women). Nocturia occurred in 3,314 individuals (33.5%). Nocturia was significantly associated with all-cause mortality (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.10-1.39) and cardiovascular disease (CVD) mortality (HR, 1.55; 95% CI, 1.19-2.01). Moreover, the mortality risk increased with increasing nocturia severity. Further analysis with propensity score matching showed that nocturia was still significantly associated with all-cause mortality and CVD mortality. In subgroup analysis according to sex, nocturia was significantly associated with allcause mortality and CVD mortality in men. In women, moderate-to-severe nocturia was significantly associated with allcause mortality and CVD mortality. In subgroup analysis according to cardio-metabolic diseases, nocturia was associated with CVD mortality in patients with diabetes mellitus, hypertension, dyslipidemia, or CVD at baseline. In subgroup analysis of patients without diabetes mellitus, hypertension or CVD, nocturia was significantly associated with all-cause mortality. CONCLUSION: Nocturia was significantly associated with mortality in men and women after adjusting for major confounding factors.

Incidence and mortality projections for major cancers among Korean men until 2034, with a focus on prostate cancer.

PURPOSE: The Korean population is rapidly aging, and the cancer burden is expected to change significantly. This study aimed to generate projections of incidence and mortality of major cancers among men in Korea until 2034, with a special focus on prostate cancer. MATERIALS AND METHODS: Cancer incidence data from 1999 to 2016 were obtained from the Korea National Cancer Incidence Database. Mortality data were obtained from Statistics Korea. The most common cancers among Korean men (stomach, colorectum, liver, lung and prostate) were analyzed. To predict the future trends of these cancers, the age-period-cohort method was conducted and extrapolated up to 2034. RESULTS: In Korean men, prostate cancer was the fourth most commonly diagnosed cancer in 2016. Based on newly diagnosed cases, the leading cancer site in the year 2034 is expected to be the lung, and the prostate is expected to be the second most frequently diagnosed cancer among Korean men. Age-standardized incidence rates of the most common cancers in men, except prostate cancer, are expected to decrease until 2034. Lung cancer is projected to remain the most common cause of cancer-related mortality until 2034, and the highest estimated change in cancer deaths is expected to be for prostate cancer. CONCLUSIONS: In Korea, the incidence and mortality of prostate cancer is expected to increase markedly in the period up to 2034, particularly in older men. Concerted efforts in screening, diagnosis, and treatment strategies should be considered by healthcare planners and providers.

Association Between Antibiotic Treatment and the Efficacy of Intravesical BCG Therapy in Patients With High-Risk Non-Muscle Invasive Bladder Cancer.

OBJECTIVE: To investigate the association between antibiotic therapy and the efficacy of intravesical BCG therapy in patients with high-risk non-muscle invasive bladder cancer (NMIBC). METHODS: This study involved the retrospective review of medical records of patients who underwent transurethral resection of bladder tumors for high-risk NMIBC followed by intravesical BCG therapy between 2008 and 2017. Patients were categorized as none, short- (2-6 days), and long-course use (≥7 days) based on the duration of antibiotic treatment concurrent with or initiated ≤30 days before BCG therapy. Oncologic outcomes, including recurrence-free survival and progression-free survival, were analyzed. RESULTS: Of the 276 patients enrolled in the study, 162 (58.7%) had pathologic T1 disease and 206 (80.2%) had high-grade disease. Concurrently with or prior to BCG therapy, 114 patients had (41.3%) received short-course antibiotic therapy, and 96 (34.8%) patients had received long-course antibiotics. The 5-year recurrence-free survival (62.2% vs 26.9%; log rank, p <0.001) and progression-free survival (79.6% vs. 53.3%; log rank, p=0.001) rates were significantly higher in patients who did not receive antibiotic therapy than in those treated with long-course antibiotics. Multivariable analysis revealed that antibiotic treatment for more than 7 days was independently associated with increased risks of recurrence (hazard ratio [HR], 2.45; 95% confidence interval [CI], 1.49-4.05; p < 0.001) and progression (HR, 3.68; 95% CI, 1.65-8.22 p = 0.001). CONCLUSION: Long-course antibiotic treatment concurrently with or prior to intravesical BCG adversely influenced disease recurrence and progression outcomes in patients with high-risk NMIBC. Careful use of antibiotics may be required to enhance the efficacy of intravesical BCG therapy. Further mechanistic and prospective studies are warranted.

Validation of the European association of urology biochemical recurrence risk groups after radical prostatectomy in an Asian cohort and suggestions for refinement.

BACKGROUND: To validate the prognostic utility of the novel European Urology Association (EAU) biochemical recurrence (BCR) risk groups in an Asian cohort and to determine whether refinement is necessary. METHODS: Two cohorts of men who experienced BCR after radical prostatectomy between 1998 and 2014 were employed. The Cox model was used to validate and model the probability of metastasis and death after BCR. Data from 817 men from the first cohort were used to develop a modified model and external validation was performed on 344 men from the second cohort. RESULTS: Distant metastasis-free survival and cancer-specific survival from the time of BCR were significantly higher in patients with a low EAU BCR risk (prostate-specific antigen doubling time [PSADT] >1 year and pathologic Gleason score [pGS] ≤7) than in high EAU BCR risk patients (PSADT ≤1 year or pGS 8-10). In the high EAU BCR risk group, survival outcomes and efficacy of early salvage radiotherapy in patients with PSADT 6-12 months and pGS ≤7 were similar to those in the low EAU BCR risk group. The C-index, which predicts metastatic progression and cancer-specific death, improved after PSADT cutoff point was modified to 6 months, and was validated externally. CONCLUSION: EAU BCR risk stratification reliably identified patients at increased risk of metastasis and cancer-specific mortality in the present cohort. Modification of the PSADT cutoff point may help to optimize the predictive performance and utility of the EAU BCR risk groups in clinical practice.

Cause of Mortality after Radical Prostatectomy and the Impact of Comorbidity in Men with Prostate Cancer: A Multi-institutional Study in Korea.

PURPOSE: This study aimed to examine the causes of death in Korean patients who underwent radical prostatectomy for prostate cancer and investigate the relationship between comorbidity and mortality. MATERIALS AND METHODS: We conducted a retrospective multicenter cohort study including 4,064 consecutive patients who had prostate cancer and underwent radical prostatectomy between January 1998 and June 2013. The primary endpoint of this study was all-cause mortality, and the secondary endpoints were cancer-specific mortality (CSM) and other-cause mortality (OCM). Charlson comorbidity index (CCI) was calculated to assess the comorbidities of each patient. RESULTS: Of 4,064 patients, 446 (11.0%) died during follow-up. The cause of death was prostate cancer in 132 patients (29.6%), other cancers in 121 patients (27.1%), and vascular disease in 57 patients (12.8%) in our cohort. The overall 10-year CSM rate was lower than the OCM rate (4.6% vs. 10.5%). The 10-year CSM rate was lower than the OCM rate in low- to intermediate-risk group patients (1.2% vs. 10.6%), whereas they were similar in high-risk group patients (11.8% vs. 10.1%). In the multivariable analysis, CCI was independently associated with all-cause mortality after radical prostatectomy, regardless of age and pathologic features. CONCLUSION: Death from prostate cancer was rare in Korean men who underwent radical prostatectomy. Clinicians should be aware of the possibility of overtreatment of low-risk prostate cancer in men with significant comorbidity. Our findings may help to facilitate counseling and plan management in this patient group.

Association of Body Composition With Survival and Treatment Efficacy in Castration-Resistant Prostate Cancer.

Objectives: The association of body composition with survival and the efficacy of first-line treatment was investigated in patients with castration-resistant prostate cancer (CRPC). Methods: The records of CRPC patients treated with docetaxel or androgen receptor signaling inhibitors (ARSi) between 2005 and 2018 were reviewed. Skeletal muscle index (SMI), visceral fat index, and subcutaneous fat index were evaluated using pretreatment computed tomography images. Results: Of 230 eligible patients, 144 received docetaxel, and 86 received ARSi as the first-line treatment for CRPC. The SMIhi (based on median values) group had higher prostate-specific antigen (PSA) progression-free survival (median 13.5 vs. 8.3 months, p = 0.030), radiologic progression-free survival (14.9 vs. 9.1 months, p < 0.001), and overall survival (24.1 vs. 16.9 months, p = 0.015) than the SMIlo group. In docetaxel-treated patients, the SMIhi group had higher PSA progression-free survival (13.5 vs. 5.9 months, p = 0.016) and radiologic progression-free survival (14.6 vs. 6.7 months, p < 0.001) than the SMIlo group. However, PSA progression-free survival and radiologic progression-free survival were comparable between the two groups in ARSi-treated patients. SMI was independently associated with the risk of radiologic progression in patients treated with docetaxel but not in those treated with ARSi. Conclusions: High skeletal muscle mass may be associated with reduced risk of disease progression and mortality in patients with CRPC. However, the significance of these relationships is limited in patients treated with docetaxel. These results suggest that assessing skeletal muscle mass may be worthwhile when selecting treatments for CRPC; however, further prospective validation and large-scale studies are needed.

Association between Postoperative Detection of Circulating Tumor Cells and Recurrence in Patients with Prostate Cancer.

PURPOSE: The clinical implications of postoperative detection of circulating tumor cells in prostate cancer are largely unknown. We investigated the association between postoperative circulating tumor cell detection after radical prostatectomy and disease recurrence in prospectively enrolled patients with prostate cancer. MATERIALS AND METHODS: A total of 203 patients with an undetectable prostate specific antigen who had undergone radical prostatectomy for prostate cancer were prospectively enrolled. Circulating tumor cell sampling was performed at a median of 4.5 months after surgery. The primary end point was biochemical recurrence-free survival. Detection of circulating tumor cells in the blood of patients was performed using a novel approach with a replication-competent adenovirus controlled by prostate specific antigen/prostate specific membrane antigen transcription regulatory elements (Ad5/35E1aPSESE4). RESULTS: Circulating tumor cells were detected in 73 (36.0%) patients with undetectable prostate specific antigen concentrations after surgery. The 3-year biochemical recurrence-free survival rate from the time of surgery was significantly higher in circulating tumor cell-negative than in circulating tumor cell-positive cases (81.6% vs 48.9%, log rank p <0.001). Multivariable analysis showed that postoperative circulating tumor cell detection was independently associated with an increased risk of biochemical recurrence (HR 5.42, 95% CI 3.24-9.06, p <0.001). C-index was increased in combinations of multivariable model and postoperative circulating tumor cell detection compared with the multivariable model alone. CONCLUSIONS: Circulating tumor cells in the blood were frequently detected in patients with undetectable prostate specific antigen levels after radical prostatectomy for localized prostate cancer. Furthermore, circulating tumor cell detection was associated with an increased risk of biochemical recurrence, suggesting that circulating tumor cell detection precedes prostate specific antigen rise after surgery in cases of prostate cancer recurrence. Large-scale validation is needed in the future.

Utility of Multiparametric Magnetic Resonance Imaging With PI-RADS, Version 2, in Patients With Prostate Cancer Eligible for Active Surveillance: Which Radiologic Characteristics Can Predict Unfavorable Disease?

BACKGROUND: We investigated the utility of multiparametric magnetic resonance imaging (mpMRI) using Prostate Imaging Reporting and Data System, version 2 (PI-RADSv2), scoring in patients with prostate cancer eligible for active surveillance (AS). MATERIALS AND METHODS: The medical records of the patients who had undergone mpMRI before radical prostatectomy from 2014 to 2018 were reviewed. All the patients had met the Prostate Cancer Research International AS criteria. PI-RADSv2 scores were assigned to 12 prostate regions. Unfavorable disease was stratified using the American Joint Committee on Cancer (AJCC) prognostic scale as stage IIB (Gleason score [GS], 3+4 and pathologic stage T2) and IIC-III (GS, ≥ 4+3 or pathologic stage T3). RESULTS: Of 376 eligible patients, 184 (48.9%), 129 (34.3%), and 63 (16.8%) had AJCC stage I, IIB, and IIC-III disease, respectively. The patients with IIC-III disease were older and had a higher prostate-specific antigen density than those with stage I or IIB disease. PI-RADS 5 lesions were more frequent in patients with stage IIC-III than in patients with stage I or IIB disease. Multivariable analysis revealed that ≥ 2 lesions with a PI-RADS 5 score was an independent predictor for unfavorable disease (hazard ratio [HR], 3.612; P < .001 for IIB; HR, 6.562; P < .001 for IIC-III), and PI-RADS score of ≥ 4 was limited for predicting AJCC stage IIB disease (HR, 2.387; P = .01). CONCLUSION: mpMRI with PI-RADSv2 showed high negative predictive value for patients with prostate cancer eligible for AS. Multiple PI-RADS 4-5 lesions were associated with unfavorable disease compared with solitary lesions. Multiple PI-RADS 5 lesions were strongly associated with GS ≥ 4+3 or pathologic T3 disease. Targeted biopsy or radical treatment should be considered for these patients.

Correction to: The small molecule WNT/ß-catenin inhibitor CWP232291 blocks the growth of castration-resistant prostate cancer by activating the endoplasmic reticulum stress pathway.

In the original publication of this article [1], there are mistakes in Fig. 4d. The corrected Fig. 4 should be.

Dihydrotestosterone promotes kidney cancer cell proliferation by activating the STAT5 pathway via androgen and glucocorticoid receptors.

PURPOSE: Androgen receptors (ARs) are expressed on a variety of cell types, and AR signaling plays an important role in tumor development and progression in several cancers. This in vitro study evaluated the effect of dihydrotestosterone (DHT) on the proliferation of renal cell carcinoma (RCC) cells in relation to AR status. METHODS: Steroid hormone receptor expression was evaluated using RT-PCR and Western blotting. The effect of DHT on cell proliferation and STAT5 phosphorylation was evaluated in RCC cell lines (Caki-2, A498, and SN12C) and primary RCC cells using cell viability assays and Western blotting. ARs and glucocorticoid receptors (GRs) were knocked down with small interfering RNAs before assessing changes in cell proliferation and STAT5 activation. RESULTS: DHT treatment promoted cell proliferation and increased STAT5 phosphorylation regardless of AR status. The AR antagonist bicalutamide reduced kidney cancer cell proliferation, regardless of AR status. AR and GR knockdown blocked STAT5 activation and reduced cell proliferation in all RCC cell lines. In patient-derived primary cells, DHT enhanced cell proliferation and this effect was diminished by treatment with the AR antagonists bicalutamide and enzalutamide and the GR antagonist mifepristone. CONCLUSION: DHT promotes cell proliferation through STAT5 activation in RCC cells, regardless of AR status. DHT appears to utilize the AR and GR pathways to activate STAT5, and the inhibition of AR and GR showed antitumor activity in RCC cells. These data suggest that targeting AR and GR may be a promising new approach to the treatment of RCC.

The small molecule WNT/ß-catenin inhibitor CWP232291 blocks the growth of castration-resistant prostate cancer by activating the endoplasmic reticulum stress pathway.

BACKGROUND: Androgen receptor (AR)-targeted treatments improve the survival of castration-resistant prostate cancer (CRPC) patients; however, secondary resistance to these agents ultimately occurs in virtually all patients. Therefore, alternative therapeutic targets are urgently needed. Since growing evidence demonstrates that WNT/ß-catenin signaling plays an important role in CRPC, the antitumor activity and mechanism of action of CWP232291, a small molecule ß-catenin inhibitor, were investigated in prostate cancer. METHODS: We assessed the antitumor activity of CWP232291 in prostate cancer cell lines and primary cells derived from CRPC patients. The effect of CWP232291 on apoptotic cell death, endoplasmic reticulum (ER) stress, cell viability, and WNT/ß-catenin signaling was evaluated by flow cytometry, western blotting, luciferase reporter assay, and fluorescence microscopy. Antitumor efficacy was assessed in two CRPC xenograft mouse models. RESULTS: CWP232291 induced ER stress, resulting in upregulation of the proapoptotic protein CHOP and activation of caspase-3-dependent apoptosis. In addition, CWP232291 suppressed the expression of ß-catenin by affecting WNT-dependent transcriptional activity, and downregulated AR and its splice variants in prostate cancer cells. Antitumor activity was observed in prostate cancer cells in vitro and ex vivo, and antitumor efficacy was observed in vivo. CONCLUSIONS: Beyond providing preclinical evidence of therapeutic efficacy for the novel small molecule ß-catenin inhibitor CWP232291 in CRPC, our results show that inducing ER stress and targeting WNT/ß-catenin signaling may be a novel strategy against CRPC.

Adjuvant chemotherapy versus observation after radical cystectomy in patients with node-positive bladder cancer.

This retrospective study compared adjuvant chemotherapy (AC) versus observation after radical cystectomy (RC) in patients with node-positive bladder cancer (pN+). Outcomes were reviewed in patients with pTanyN1-3M0 bladder cancer who underwent RC with or without AC between 1995 and 2017. Baseline characteristics between the two groups were controlled with inverse probability of treatment weighting (IPTW)-adjusted analyses. Of 281 enrolled patients, the 3-year IPTW-adjusted rates of overall survival was higher in the AC group than the RC group (46.4% vs. 33.7%, p = 0.024). AC was an independent predictor of overall survival (hazard ratio = 0.48; P < 0.0001). When patients were subdivided by lymph node density (LND), the 3-year overall survival rates were similar between the AC and RC groups in patients with LND < 9%, but higher in the AC group in patients with LND 9-25% (53.4% vs. 23.7%) and LND ≥ 25% (27.4% vs. 16.1%). The numbers needed to treat to prevent one death at 3 years were three and nine in patients with LND 9-25% and ≥25%, respectively. In conclusion, AC after RC was associated with improved overall survival in patients with node-positive bladder cancer. Patients with an intermediate nodal burden may benefit most from AC.