Early experience with Watson for Oncology: a clinical decision-support system for prostate cancer treatment recommendations.

PURPOSE: Urological oncologists have difficulty providing optimal personalized care due to rapid alterations in scientific research results, medical advancements, and treatment guidelines. IBM's Watson for Oncology (WFO) is an artificial intelligence clinical decision-support system that assists oncologists with evidence-based treatment recommendations. In the present study, we examined the level of concordance between the treatment recommendations for prostate cancer according to WFO and the actual treatments that the patients received in the department of urology. METHODS: We enrolled 201 patients who received prostate cancer treatment between January 2018 and June 2018. WFO provided treatment recommendations using clinical data in three categories: recommended, for consideration, and not recommended. These were compared with the actual treatments received by patients. Prostate cancer treatments were considered concordant if the received treatments were included in the "recommended" or "for consideration" categories by WFO. RESULTS: The patients' mean age was 71.2 years. There were 60 (29.9%) and 114 (56.7%) patients with an Eastern Cooperative Oncology Group (ECOG) performance score ≥ 1 and non-organ confined disease (stage III/IV), respectively. The overall prostate cancer treatment concordance rate was 73.6% ("recommended": 53.2%; "for consideration": 20.4%). An ECOG performance score ≥ 1 and older age (≥ 75 years) were significantly associated with discordance (p = 0.001 and p = 0.026, respectively) on multivariate analysis. CONCLUSION: In the present study, the treatment recommendations by WFO and the actual received treatments in the department of urology showed a relatively high concordance rate in prostate cancer patients.

Effect of pre-operative internal obturator muscle mass index in MRI on biochemical recurrence of prostate cancer patients after radical prostatectomy: a multi-center study.

BACKGROUND: Recent reports show that the pre-operative or post-operative skeletal mass index (sarcopenia) affects survival rates for various cancers; however, the link between prostate cancer survival and sarcopenia is unclear. Therefore, this study examined the effect of the pre-operative internal obturator muscle (IOM) mass index on biochemical recurrence (BCR) of prostate cancer (PCa) patients who underwent radical prostatectomy. METHODS: In total, 222 patients, who underwent open, laparoscopic, or robot-assisted radical prostatectomy at seven centers in 2011 and were followed up for 5 years, were enrolled. BCR was examined in the context of pre-operative IOM mass index and BMI. RESULTS: The mean age of the patients was 67.82 ± 6.23 years, and the mean pre-operative prostate-specific antigen (PSA) level was 11.61 ± 13.22 ng/ml. There was no significant difference in baseline characteristics between the low and high IOM mass index groups (p > 0.05). Age, pre-op PSA level, ECE, and T-stage were associated with BCR (p = 0.049, p < 0.001, p = 0.001, p = 0.004, respectively). BMI, prostate volume, Gleason score, resection margin, N-stage, M-stage and IOM mass index was not associated with BCR (p > 0.05). CONCLUSIONS: Pre-operative IOM mass index was not associated with BCR; however, long-term follow-up is necessary to evaluate cancer-specific and overall survival of PCa patients.

Lysophosphatidic Acid Upregulates Recepteur D'origine Nantais Expression and Cell Invasion via Egr-1, AP-1, and NF-κB Signaling in Bladder Carcinoma Cells.

Muscle invasive bladder carcinoma is a highly malignant cancer with a high mortality rate, due to its tendency to metastasize. The tyrosine kinase recepteur d'origine nantais (RON) promotes bladder carcinoma metastasis. Lysophosphatidic acid (LPA) is a phospholipid derivative, which acts as a signaling molecule to activate three high affinity G-protein coupled receptors, LPA1, LPA2, and LPA3. This in turn leads to cell proliferation and contributes to oncogenesis. However, little is known about the effects of LPA on invasive bladder cancer (IBC). In this study, we discovered that LPA upregulated RON expression, which in turn promoted cell invasion in bladder cancer T24 cells. As expected, we found that the LPA receptor was essential for the LPA induced increase in RON expression. More interestingly, we discovered that LPA induced RON expression via the MAPK (ERK1/2, JNK1/2), Egr-1, AP-1, and NF-κB signaling axes. These results provide experimental evidence and novel insights regarding bladder malignancy metastasis, which could be helpful for developing new therapeutic strategies for IBC treatment.

Mirabegron as a treatment for overactive bladder symptoms in men (MIRACLE study): Efficacy and safety results from a multicenter, randomized, double-blind, placebo-controlled, parallel comparison phase IV study.

AIMS: To evaluate the efficacy and safety of mirabegron in males with overactive bladder (OAB) symptoms. METHODS: In total, 464 males with OAB symptoms were enrolled from 14 institutes and were sorted into either the mirabegron 50 mg (n = 310) or placebo (n = 154) groups. The change in (i) the mean number of 24-h micturition episodes; (ii) OAB Symptom Scale (OABSS); and (iii) International Prostate Symptom Score (IPSS) from baseline to 12 weeks of treatment were compared between the two groups. Safety assessments included treatment-emergent adverse events, blood pressure, pulse rate, postvoid residual volume, and maximum urinary flow rate. After 12 weeks, the study was extended for 14 additional weeks by administering mirabegron 50 mg to both groups. RESULTS: The reduction in the mean number of 24-h micturition episodes from baseline to 12 weeks of treatment was similar between the two groups. However, significantly greater changes from baseline to 12 weeks were observed in total OABSS, OABSS urgency incontinence score (Q4), IPSS storage subscore (Q2 + Q4 + Q7), and IPSS urgency score (Q4) in the mirabegron group (P = 0.01 for all). According to the extended study, the changes of all efficacy variables from baseline to 26 weeks were similar between both groups. The safety assessment results were also similar between the two groups at 12 and 26 weeks. CONCLUSION: A daily 50 mg dose of mirabegron for 12 weeks reduced OAB symptoms in men, and no significant adverse events compared to the placebo group were noted.

Primary renal angiosarcoma with extensive hemorrhage: CT and MRI findings.

Primary angiosarcomas of the kidney are very rare, but highly aggressive tumors showing poor prognosis. Patients frequently complain of flank pain, hematuria, or a palpable mass. We present a case of primary renal angiosarcoma occurring in a 61-year-old man. CT images depicted a huge exophytic mass (16 cm in diameter) in the right kidney, exhibiting extensive hemorrhage. The mass showed centripetal peripheral nodular enhancement on dynamic contrast-enhanced images. Furthermore, MR imaging revealed a tangled mesh of tumor vessels in the periphery of the mass. We suggest its inclusion in the differential diagnosis of cases of hemorrhagic renal tumors with prominent vasculature.

Laparoscopic adrenalectomy using the lateral retroperitoneal approach: Is it a safe and feasible treatment option for pheochromocytomas larger than 6 cm?

OBJECTIVES: To evaluate the surgical feasibility of laparoscopic adrenalectomy using the lateral retroperitoneal approach for the treatment of large pheochromocytomas, and to identify the preoperative risk factors for intraoperative hypertension. METHODS: We retrospectively reviewed 51 patients who underwent laparoscopic adrenalectomy using the lateral retroperitoneal approach for the treatment of pheochromocytomas. Patient characteristics and perioperative outcomes were analyzed and compared between the two study groups based on tumor size: group A (n = 27, ≤6 cm) and group B (n = 24, ˃6 cm). RESULTS: There was no significant difference in preoperative characteristics between the two groups except for tumor size (P = 0.001) and urinary metanephrine (P = 0.011). Group B patients required longer operating time (P = 0.008), had a greater estimated blood loss (P = 0.001) and hemoglobin change (P = 0.002). However, no significant differences were observed in perioperative complications and mortality. Multivariate analysis showed that symptomatic pheochromocytomas (P = 0.004) and tumor size (P = 0.007) were significant risk factors for intraoperative hypertension. CONCLUSIONS: Laparoscopic adrenalectomy using the lateral retroperitoneal approach for pheochromocytomas can be regarded as a treatment option, even for tumors measuring >6 cm. Symptomatic pheochromocytomas and large tumor size seem to represent risk factors for intraoperative hypertension.

A rare presentation of metastatic prostate cancer, initially a suspect for urothelial cell carcinoma of the ureter: a case report.

BACKGROUND: The most common metastatic sites of prostate cancer are the lymph nodes and bone. Ureteral metastasis from prostate cancer is very unusual and only a few cases have been reported. CASE PRESENTATION: We describe a 76-year-old male with ureteral metastasis of prostate cancer along with a review of the literature. Initially, based on the diagnostic evaluation, urothelial cell carcinoma of the left distal ureter was suspected. Nephroureterectomy with bladder cuff excision was performed. The final pathologic diagnosis was prostate cancer metastatic to the ureter. CONCLUSION: Although rare and the mechanistic link between prostate cancer and distant ureteral metastasis has not been clarified on a clinical basis, this would be included in the differential diagnosis of ureteral lesions in patients with a history of prostate cancer. It is important to recognize this unusual manifestation so that timely appropriate treatment can be initiated.

Carcinoid tumor associated with adjacent dysplastic columnar epithelium in the renal pelvis: A case report and literature review.

Carcinoid tumors are well documented in the pulmonary and gastrointestinal systems, but very rare in the urinary tract, especially in the renal pelvis. We report on a 60-year-old female patient who presented with left flank pain and fever. Abdominal computed tomography demonstrated a heterogeneously enhancing mass in the left renal pelvis and a stone at the left proximal ureter. Multiple parenchymal lesions were also observed, which were identified as uneven caliectasis displaying air-fluid levels and renal parenchymal atrophy. The patient underwent simple nephro-ureterectomy. Macroscopically, a polypoid mass was observed in the renal pelvis. Microscopically, the tumor revealed acinar, tubular, and solid pattern and was composed of small, monotonous and hyperchromatic cells. Lining epithelia in renal pelvis and ureter revealed columnar epithelia with dysplastic change. The tumor cells were positive for chromogranin A, synaptophysin, CD56, and focally positive for cytokeratin. Immunohistochemical staining of synaptophysin and chromogranin A highlighted the neuroendocrine cells in the columnar epithelium. Ki-67 (1:50; MIB-1) labeling index was less than 1% in the area with highest uptake. We report here a case of carcinoid tumor of the renal pelvis that was associated with adjacent dysplastic columnar epithelium.

Prostate-Specific Antigen fluctuation: what does it mean in diagnosis of prostate cancer?

OBJECTIVE: To investigate whether prostate-specific antigen (PSA) fluctuation correlates with a prostate cancer and to assess whether PSA fluctuation could be used for diagnosis of prostate cancer. MATERIALS AND METHODS: Our study included 229 patients who were performed a prostate biopsy (non-cancer group, 177; prostate cancer group, 52). Enrolled patients were provided twice PSA tests within 6 months. PSA fluctuation (%/month) was defined as a change rate of PSA per a month. Independent t test was used to compare between two groups. Receiver operator characteristic curve was used to assess the availability as a differential diagnostic tool and the correlation. Simple linear regression was performed to analyze a correlation between PSA fluctuation and other factors such as age, PSA, PSA density, and prostate volume. RESULTS: There were significant differences in PSA, PSA density, percentage of free PSA, and PSA fluctuation between two groups. PSA fluctuation was significantly greater in non-cancer group than prostate cancer group (19.95 ± 23.34%/month vs 9.63 ± 8.57%/ month, P=0.004). The most optimal cut-off value of PSA fluctuation was defined as 8.48%/month (sensitivity, 61.6%; specificity, 59.6%; AUC, 0.633; P=0.004). In a simple linear regression model, only PSA level was significantly correlated with PSA fluctuation. CONCLUSION: Patients with wide PSA fluctuations, although baseline PSA levels are high, might have a low risk of diagnosis with prostate cancer. Thus, serial PSA measurements could be an option in patients with an elevated PSA level.

Is larger tumor size a contraindication to retroperitoneal laparoscopic adrenalectomy?

PURPOSE: To evaluate the surgical feasibility of retroperitoneal laparoscopic adrenalectomy for tumors exceeding 5 cm. METHODS: A retrospective review was carried out on all adrenalectomies performed between 2002 and 2011. All surgical procedures were performed or supervised by one of two experienced laparoscopic surgeons. A total of 133 patients who underwent retroperitoneal laparoscopic adrenalectomy were divided according to tumor size: group I (n = 57) had tumors <5 cm and group II (n = 76) had tumors ≥5 cm. The operative outcomes included surgical time, change in hemoglobin level, estimated blood loss, necessity for blood transfusion, time to ambulation, hospitalization duration, postoperative complications according to the Clavien-Dindo classification, and the rate of conversion to open surgery. RESULTS: The estimated blood loss (271.75 ± 232.98 mL vs. 367.24 ± 275.11 mL; p = 0.037), time to ambulation (1.60 ± 0.49 days vs. 1.89 ± 0.31 days; p = 0.001), and postoperative hospitalization (7.88 ± 3.08 days vs. 9.264 ± 3.10 days; p = 0.012) were significantly higher in group II. The operation time and hemoglobin level change were not statistically different between groups. Blood transfusions were performed in 3 patients from group I and 6 patients from group II (5.3 vs. 7.9 %; p = 0.449). No patients experienced conversion to open surgery. CONCLUSIONS: Retroperitoneal laparoscopic adrenalectomy can be used in patients with tumors larger than 5 cm.

Prognostic factors for recurrence-free and overall survival after adrenalectomy for metastatic carcinoma: a retrospective cohort pilot study.

BACKGROUND: The survival benefits of adrenalectomy (ADx) in the setting of metastatic cancer and prognostic factors for recurrence-free (RFS) and overall survival (OS) after adrenalectomy for metastatic carcinoma are still under debate. We evaluated the impact of clinicopathological variables on RFS and OS after ADx for metastatic carcinoma in patients with primary cancer. METHODS: A total of 32 patients undergoing ADx for metastatic cancer between 2004 and 2012 at two tertiary medical centers. Metastases were regarded as synchronous (<6 months) or metachronous (≥6 months) depending on the interval after primary surgery. Associations of perioperative clinicopathologic variables with RFS and OS were analyzed using Cox regression models. RESULTS: In total, 32 patients received ADx for metastatic primary tumors located in the lung (n = 11), colon (n = 4), liver (n = 5), stomach (n = 3), kidney (n = 4), pancreas (n = 2), glottis, esophagus, cervix, and ovary (n = 1 each). The overall recurrence rate after adrenalectomy was 62.5% (n = 20). By univariate analysis, C-reactive protein, inflammation-based prognosis score, and adrenalectomy for curative intent were associated with RFS and OS. Independent prognostic factors for shorter RFS were operative method (laparoscopy HR 4.68, 95% CI 1.61-13.61, p = 0.005) and inflammation-based prognostic score (HR 11.8, 95% CI 2.50-55.7, p = 0.002). For shorter OS, synchronous metastasis (HR 3.05, 95% CI 1.07-11.94, p = 0.048) and inflammation-based prognostic score (HR 6.65, 95% CI 1.25-35.23, p = 0.026) were identified as independent prognostic factors. CONCLUSIONS: Our pilot study suggests that synchronous disease and inflammation-based prognostic score are significant prognostic factors for survival and should be considered when performing ADx for metastatic diseases.

Early pyeloplasty for recovery of parenchymal thickness in children with unilateral ureteropelvic junction obstruction.

OBJECTIVE: We compared renal function before and after pyeloplasty in children with unilateral ureteropelvic junction obstruction (UPJO) according to the children's age. METHODS: We reviewed the medical records of 36 children with UPJO who had undergone pyeloplasty and showed improved urine drainage on postoperative diuretic renal scan. The children were divided into two groups according to their age at the time of surgery: group I, ≤1 year of age (n = 15), and group II, >1 year of age (n = 21). Parenchymal thickness (PT) and pelvic anteroposterior diameter measured by ultrasonography and renal function measured by (99m)Tc-MAG3 renal scan were compared before and after surgery. RESULTS: Group I patients, who underwent pyeloplasty within 1 year of birth, showed significant recovery of the PT ratio at follow-up evaluation (from 0.50 ± 0.13 preoperatively to 0.83 ± 0.23 postoperatively; p = 0.029) compared with that in group II (from 0.74 ± 0.23 preoperatively to 0.75 ± 0.18 postoperatively; NS). The mean differences in the PT ratio before and after surgery were 0.29 ± 0.25 and 0.02 ± 0.18 in groups I and II, respectively. CONCLUSION: This result suggests that early surgery improves subsequent parenchymal growth of the involved renal unit.

FGFR3 Mutations in Urothelial Carcinoma: A Single-Center Study Using Next-Generation Sequencing.

Background: Mutations of fibroblast growth factor receptor 3 (FGFR3) are associated with urothelial carcinoma (UC) oncogenesis and are considered an important therapeutic target. Therefore, we evaluated the FGFR3 mutation rate and its clinical significance in urothelial carcinoma (UC) using next-generation sequencing. Methods: A total of 123 patients with UC who were treated at Chonnam National University Hospital (Gwang-ju, Korea) from January 2018 to December 2020 were enrolled. We performed NGS using the Oncomine panel with tumor specimens and blood samples corresponding to each specimen. We analyzed the FGFR3 mutation results according to the type of UC and the effects on early recurrence and progression. Results: The mean age of the patients was 71.39 ± 9.33 years, and 103 patients (83.7%) were male. Overall, the FGFR3 mutation rate was 30.1% (37 patients). The FGFR3 mutation rate was the highest in the non-muscle-invasive bladder cancer (NMIBC) group (45.1%), followed by the muscle-invasive bladder cancer (22.7%) and upper tract UC (UTUC) (14.3%) groups. Patients with FGFR3 mutations had a significantly lower disease stage (p = 0.019) but a high-risk of NMIBC (p < 0.001). Conclusions: Our results revealed that FGFR3 mutations were more prevalent in patients with NMIBC and lower stage UC and associated with a high-risk of NMIBC. Large multicenter studies are needed to clarify the clinical significance of FGFR3 mutations in UC.

Five-alpha reductase inhibitor influences expression of androgen receptor and HOXB13 in human hyperplastic prostate tissue.

OBJECTIVES: Five-alpha reductase inhibitors (5ARIs) are known as chemopreventive agents in prostate cancer with a risk of high-grade disease. This study evaluated the effects of 5ARI on androgen receptor (AR) and proteins involved in prostate cell growth such as HOXB13 expression in human prostate tissue and LNCaP prostate cancer cells. MATERIALS AND METHODS: We retrospectively selected 21 patients who underwent TURP between March 2007 and February 2010 for previously confirmed BPH by prostate biopsy. They were grouped into control (group 1, n = 9) and 5ARI treatment (group 2, n = 12) before TURP. AR and HOXB13 expression in prostate tissue was evaluated by immunohistochemical staining. We tested the effect of 5ARI on the expression of AR, prostate specific antigen (PSA) and HOXB13 in LNCaP cells. Cells were assessed by Western blot analysis, MTT in vitro proliferation assay, and ELISA. RESULTS: Group 2 showed stronger reactivity for AR and HOXB13 than those of the group 1. MTT assay showed death of LNCaP cells at 25uM of 5ARI. At the same time, ELISA assay for PSA showed that 5ARI inhibited secretion of PSA in LNCaP cells. Western blot analysis showed that 5ARI did not greatly alter AR expression but it stimulated the expression of HOXB13. CONCLUSIONS: These results demonstrated that 5ARI influences AR and HOXB13 expression in both LNCaP cells and human prostate tissue. In order to use 5ARI in chemoprevention of prostate cancer, we still need to clarify the influence of 5ARI in ARs and oncogenic proteins and its regulation pathway.

Initial experience of transurethral resection with pediatric resectoscope for incomplete anterior urethral stricture.

PURPOSE: Endoscopic urethrotomy is an alternative method in treatment of urethral stricture. However, it have high recurrence rate because of the remained fibrotic tissue. Removal of the fibrotic tissue can maintain the patency of the urethral lumen after the procedure. We report the therapeutic efficacy of our initial experience using pediatric resectoscope for treating anterior urethral stricture in 16 cases. MATERIALS AND METHODS: From January 2009 to April 2011, transurethral resection with pediatric resectoscope was primarily performed on 16 patients with anterior urethral stricture. Retrograde urethrography, uroflowmetry, postvoid residual volume, IPSS score and QoL score were performed preoperatively. We used 11.5Fr pediatric resectoscope (Wolf) and monopolar electrosurgical generator. The stricture was incised under vision at the 12 o'clock location or the site of maximum scar tissue or narrowing in asymmetric strictures for working space. After incision, transurethral resection with pediatric resectoscope was performed to all scar tissues. Monopolar cutting current was set on 45 watt and coagulation current was set on 30 watt, fulgurate mode. Postoperatively, drainage of the bladder was performed for 7 days using an 18F latex catheter. Patients were followed up by IPSS score, QoL score, uroflowmetry and postvoid residual volume. RESULTS: Successful results without recurrence were achieved in 11 of 16 patients. Postoperative urethral dilation had been performed average 2.4 times (0~6 times). When we classified the results by etiology, the number of successful results in strictures with a trauma, iatrogenic, or unknown cause was 5 (7/11), 3 (3/4) and 1 (1/1), respectively. In 5 patients who failed treatment, we repeated transurethral resection with pediatric resectoscope in 1 patient, and periodic urethral dilation in 4 patients. No operative complications occurred in any patients. CONCLUSIONS: Transurethral resection with pediatric resectoscope is an effective therapeutic method for anterior urethral stricture. More long-term follow-up and large scale studies are needed to confirm the efficacy of this procedure.

Significance of Glucose Control for Perioperative and Long-Term Renal Functions after Nephron-sparing Surgery for Renal Cancer in Patients with Diabetes.

PURPOSE: This study aimed to evaluate the predictive factors for perioperative and long-term renal functions after nephron-sparing surgery (NSS). MATERIALS AND METHODS: The clinical records of 379 patients who underwent NSS for a single renal tumor with a normal contralateral kidney between 2009 and 2016 were retrospectively analyzed. After surgery, the occurrence of acute kidney injury (AKI) within 7 days and the progression of chronic kidney disease (CKD) 5 years later were assessed using serum creatinine (S-Cr) levels. Perioperative AKI was defined as an increase in the S-Cr level by ≥ 0.3 mg/dL or 1.5-1.9 times the baseline value. CKD was defined as the estimated glomerular filtration rate (eGFR) decreasing from > 60 mL/min/1.73 m2 to < 60 mL/min/1.73 m2. RESULTS: Changes in the eGFR were assessed during 5 years after surgery. Among 379 patients, 81 (21.4%) patients presented diabetes mellitus (DM), and 30 (7.92%) experienced uncontrolled DM. The AKI occurrence and CKD progression were observed in 50 (13.2%) patients and 79 (20.8%) patients, respectively. Multivariable analyses revealed that female gender (95% confidence interval [CI]: 0.16-0.91, odds ratio [OR] = 0.39, P = 0.029), uncontrolled DM (95% CI: 1.05-6.60, OR = 2.63, P = 0.039), and intermediate NePhRO score (95% CI: 1.07-3.80, OR = 2.02, P = 0.03) were associated with perioperative AKI. In addition, old age (95% CI: 1.10-1.18, OR = 1.14, P < 0.001) and uncontrolled DM (95% CI: 1.84-11.4, OR = 4.57, P = 0.001) were associated with long-term CKD progression. CONCLUSION: Uncontrolled DM is the only predictive factor for perioperative and long-term renal functions after nephron-sparing surgery.

Somatic Mutation of the Non-Muscle-Invasive Bladder Cancer Associated with Early Recurrence.

Next-generation sequencing (NGS) is widely used in muscle-invasive bladder cancer but has limited use in non-muscle-invasive bladder cancer (NMIBC) due to significant heterogeneity and high cancer-specific survival. Therefore, we evaluated the genomic information of NMIBC and identified molecular alterations associated with tumour recurrence. A total of 43 patients with NMIBC who underwent transurethral resection of the bladder were enrolled. We performed NGS using an Oncomine panel of tumour specimens and blood samples corresponding to each specimen. The somatic mutation results were analysed by pairwise comparison and logistic regression according to the recurrence of bladder tumours within 1 year. The median incidence of genetic variations in 43 tumour samples was 56 variations per sample, and a high tumour mutation burden (TMB) was associated with tumour recurrence (median variation 33 vs. 64, p = 0.023). The most mutated gene was adipose tissue macrophages (ATM) (79%), followed by neurofibromatosis-1 (NF1) (79%), and neurogenic locus notch homolog protein 1 (NOTCH1) (79%). In multivariable analysis, mutation of epidermal growth factor receptor (EGFR) (odds ratio [OR], 9.95; 95% confidence interval [CI], 1.40-70.96; p = 0.022) and telomerase reverse transcriptase (TERT) (OR, 7.92; 95% CI, 1.22-51.51; p = 0.030) were significant factors associated with the recurrence of bladder tumour within 1 year. Our results revealed that high TMB, EGFR mutation, and TERT mutation had a significant association with tumour recurrence in NMIBC. In addition, somatic mutations in EGFR and TERT could be useful prognostic biomarkers in NMIBC.

Tc-99m DMSA SPECT for Follow-Up of Non-Operative Treatments in Renal Injuries: A Prospective Single-Center Study.

OBJECTIVE: The assessment of cortical integrity following renal injuries with planar Tc-99m dimercaptosuccinic acid (DMSA) scintigraphy depends on measuring relatively decreased cortical uptake (i.e., split renal function [SRF]). We analyzed the additive values of the volumetric and quantitative analyses of the residual cortical integrity using single-photon emission computed tomography (SPECT) compared to the planar scintigraphy. MATERIALS AND METHODS: This prospective study included 47 patients (male:female, 32:15; age, 47 ± 22 years) who had non-operatively managed renal injuries and underwent DMSA planar and SPECT imaging 3-6 months after the index injury. In addition to planar SRF, SPECT SRF, cortical volume, and absolute cortical uptake were measured for the injured kidney and both kidneys together. The correlations of planar SRF with SPECT SRF and those of SRF with volumetric/quantitative parameters obtained with SPECT were analyzed. The association of SPECT parameters with renal function, grades of renal injuries, and the risk of renal failure was also analyzed. RESULTS: SPECT SRF was significantly lower than planar SRF, with particularly higher biases in severe renal injuries. Planar and SPECT SRF (dichotomized with a cutoff of 45%) showed 19%-36% of discrepancies with volumetric and quantitative DMSA indices (when dichotomized as either high or low). Absolute cortical uptake of the injured kidney best correlated with glomerular filtration rate (GFR) at follow-up (ρ = 0.687, P < 0.001) with significant stepwise decreases by GFR strata (90 and 60 mL/min/1.73 m²). Total renal cortical uptake was significantly lower in patients with moderate-to-high risk of renal failure than those with low risk. However, SRF did not reflect GFR decrease below 60 mL/min/1.73 m² or the risk of renal failure, regardless of planar or SPECT (count- or volume-based SRF) imaging. CONCLUSION: Quantitative measurements of renal cortical integrity assessed with DMSA SPECT can provide more clinically relevant and comprehensive information than planar imaging or SRF alone.

Apalutamide for metastatic castration-sensitive prostate cancer: final analysis of the Asian subpopulation in the TITAN trial.

The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial showed improvement in overall survival (OS) and other efficacy endpoints with apalutamide plus androgen deprivation therapy (ADT) versus ADT alone in patients with metastatic castration-sensitive prostate cancer (mCSPC). As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer, a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation. Event-driven endpoints were OS, and time from randomization to initiation of castration resistance, prostate-specific antigen (PSA) progression, and second progression-free survival (PFS2) on first subsequent therapy or death. Efficacy endpoints were assessed using the Kaplan-Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity. Participating Asian patients received once-daily apalutamide 240 mg ( n = 111) or placebo ( n = 110) plus ADT. After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide, apalutamide reduced the risk of death by 32% (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.42-1.13), risk of castration resistance by 69% (HR: 0.31; 95% CI: 0.21-0.46), PSA progression by 79% (HR: 0.21; 95% CI: 0.13-0.35) and PFS2 by 24% (HR: 0.76; 95% CI: 0.44-1.29) relative to placebo. The outcomes were comparable between subgroups with low- and high-volume disease at baseline. No new safety issues were identified. Apalutamide provides valuable clinical benefits to Asian patients with mCSPC, with an efficacy and safety profile consistent with that in the overall patient population.

A prospective, multicenter study on the clinical effectiveness of abiraterone in metastatic castration-resistant prostate cancer in Korea: Pre- vs. post-chemotherapy.

PURPOSE: The proper treatment sequence for administering abiraterone acetate plus prednisolone (AAP) and chemotherapeutic agents has not yet been elucidated for metastatic castration-resistant prostate cancer (mCRPC). Hence, this study evaluated the effectiveness and safety of AAP in pre- and post-chemotherapy settings using real-world data. MATERIALS AND METHODS: This prospective, multicenter, open-label, observational study included 506 patients with mCRPC. Patients were classified according to the timing of chemotherapy into pre- and post-chemotherapy groups. The effectiveness and safety of AAP were compared between the groups; the prostate-specific antigen (PSA) response, PSA progression-free survival, and radiologic progression-free survival were assessed; and adverse drug reactions were recorded. RESULTS: Among the included patients, 319 and 187 belonged to the pre- and post-chemotherapy groups, respectively. Risk classification was similar between the two groups. The PSA response was 61.8% in the pre-chemotherapy group and 39.0% in the post-chemotherapy group (p<0.001). The median time to PSA progression (5.00 vs. 2.93 mo, p=0.001) and radiologic progression-free survival (11.84 vs. 9.17 mo, p=0.002) were significantly longer in the pre-chemotherapy group. Chemotherapy status was associated with PSA (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.09-1.77) and radiologic progression (HR 1.66, 95% CI 1.18-2.33) during AAP treatment. Adverse drug reactions were reported at similar frequencies in both groups. CONCLUSIONS: In this postmarketing surveillance, AAP benefited patients with mCRPC, especially in settings before chemotherapy was administered, resulting in a high PSA response and longer PSA and radiologic progression-free survival with tolerable adverse drug reactions.