Psoas mass index at the level of the third lumbar vertebra on computed tomography is a prognostic predictor for metastatic castration-sensitive prostate cancer.

BACKGROUND: Computed tomography-defined low skeletal muscle mass is associated with oncological outcomes in patients with prostate cancer. However, its association with the outcomes of hormone-treated metastatic castration-sensitive prostate cancer remains unclear. We aimed to determine the association between metastatic castration-sensitive prostate cancer and psoas muscle parameters. METHODS: We retrospectively reviewed 121 patients with N1 and/or M1 metastatic castration-sensitive prostate cancer who underwent primary androgen deprivation therapy between 2005 and 2021, either by administration of luteinizing hormone-releasing hormone agonist/antagonist or by surgical castration accompanied by bicalutamide, a first-generation antiandrogen. Before treatment administration, the psoas muscle index at the level of the third lumbar vertebra (psoas muscle area [cm2]/height2 [m2]) and the mean Hounsfield units of the psoas muscle were evaluated using non-contrast computed tomography and in relation to oncological outcomes. RESULTS: The median follow-up was 56.9 months. Furthermore, during follow-up, 82 (67.7%) and 53 (43.8%) patients progressed to castration-resistant prostate cancer and died, respectively. Multivariate analysis of castration-resistant prostate cancer-free survival and overall survival showed significant differences in the Gleason score, clinical N-stage, and psoas muscle index (median cutoff: 3.044 cm2/m2). CONCLUSIONS: Pretreatment psoas muscle index is an independent predictor of poor castration-resistant prostate cancer-free survival and overall survival in patients with N1 and/or M1 metastatic castration-sensitive prostate cancer.

Postoperative complications and determinant of selecting non intracorporeal urinary diversion in patients undergoing robot-assisted radical cystectomy: an initial experience.

Background: Robot-assisted radical cystectomy (RARC) with urinary diversion has become a standard surgical procedure because of its three-dimensional high-definition surgical field of view, flexibility, and stability. However, because of the highly complex steps of surgery, postoperative complications cannot be ignored. Methods: This retrospective, single-center, observational cohort study investigated the postoperative complications following RARC at a non-high-volume center in Japan. From August 2019 to March 2023, 50 consecutive patients who underwent RARC for histologically proven muscle-invasive bladder cancer (MIBC) or high-risk non-MIBC with an indication for radical cystectomy according to the Japanese Urological Association Guideline 2019 were included. Factors correlated with the selection of extracorporeal urinary diversion (ECUD) or cutaneous ureterostomy rather than intracorporeal urinary diversion (ICUD) for urinary diversion were also investigated. Results: In total, 33 (66%) and 31 (62%) patients experienced complications during the first 90 and 30 days after RARC, respectively. Among them, 19 (38%) and 18 (36%) patients developed Clavien-Dindo classification G2 complications, and 12 (24%) and 11 (22%) developed G3 or higher (major) complications during the first 90 and 30 days after RARC, respectively. The most common complications were gastrointestinal complications (26%) and urinary tract infections (22%). Nine patients (18%) underwent surgical intervention within 90 days of undergoing RARC. Higher infusion volume during the operations was significantly correlated with the occurrence of major complications within 90 days (P=0.025) and 30 days (P=0.0158) after RARC. Nineteen patients (38%) underwent non-ICUD. Twelve patients received ECUD as an ileal conduit or neobladder, and among them, three patients received ECUD due to intraabdominal adhesion for previous abdominal surgery or radiation, while four patients received ECUD ileal conduit due to comorbidities and advanced cases (palliative surgery) to shorten the surgery time. Conclusions: Surgical complications related to the initial experience with RARC at a non-high-volume center in Japan cannot be ignored. Although this complicated surgical procedure requires a learning curve to achieve a stable rate of much fewer major complications after RARC, careful assessment of patients' status before surgery and critical postoperative management may reduce complication rates more quickly, even at non-high-volume centers.

Prognostic impact of histological discordance between transurethral resection and radical cystectomy.

OBJECTIVE: To analyse the impact of histological discordance of subtypes (subtypes or divergent differentiation [DD]) in specimens from transurethral resection (TUR) and radical cystectomy (RC) on the outcome of the patients with bladder cancer receiving RC. PATIENTS AND METHODS: We analysed data for 2570 patients from a Japanese nationwide cohort with bladder cancer treated with RC between January 2013 and December 2019 at 36 institutions. The non-urinary tract recurrence-free survival (NUTR-FS) and overall survival (OS) stratified by TUR or RC specimen histology were determined. We also elucidated the predictive factors for OS in patients with subtype/DD bladder cancer. RESULTS: At median follow-up of 36.9 months, 835 (32.4%) patients had NUTR, and 691 (26.9%) died. No statistically significant disparities in OS or NUTR-FS were observed when TUR specimens were classified as pure-urothelial carcinoma (UC), subtypes, DD, or non-UC. Among 2449 patients diagnosed with pure-UC or subtype/DD in their TUR specimens, there was discordance between the pathological diagnosis in TUR and RC specimens. Histological subtypes in RC specimens had a significant prognostic impact. When we focused on 345 patients with subtype/DD in TUR specimens, a multivariate Cox regression analysis identified pre-RC neutrophil-lymphocyte ratio and pathological stage as independent prognostic factors for OS (P = 0.016 and P = 0.001, respectively). The presence of sarcomatoid subtype in TUR specimens and lymphovascular invasion in RC specimens had a marginal effect (P = 0.069 and P = 0.056, respectively). CONCLUSION: This study demonstrated that the presence of subtype/DD in RC specimens but not in TUR specimens indicated a poor prognosis. In patients with subtype/DD in TUR specimens, pre-RC neutrophil-lymphocyte ratio and pathological stage were independent prognostic factors for OS.

Clinical Efficacy and Openness to New Challenges of Low Dose Rate Brachytherapy for Prostate Cancer.

Over a century ago, low-dose-rate (LDR) brachytherapy was introduced to treat prostate cancer (PCa). Since then, it has been widely applied worldwide, including in East Asia. LDR brachytherapy has been performed in 88 institutes in Japan. Beneficial clinical outcomes of LDR brachytherapy for intermediate-to-high-risk PCa have been demonstrated in large clinical trials. These clinical outcomes were achieved through advances in methods, such as urological precise needle puncture and seed placement, and the quantitative decision making regarding radiological parameters by radiation oncologists. The combined use of LDR brachytherapy with other therapeutic modalities, such as external beam radiation and androgen deprivation therapy, for the clinical risk classification of PCa has led to better anticancer treatment efficacy. In this study, we summarized basic LDR brachytherapy findings that should remain unchanged and be passed down in urology departments. We also discussed the applications of LDR brachytherapy for PCa in various clinical settings, including focal and salvage therapies. In addition, we highlighted technologies associated with brachytherapy that are under development.

Roles of the PARP Inhibitor in BRCA1 and BRCA2 Pathogenic Mutated Metastatic Prostate Cancer: Direct Functions and Modification of the Tumor Microenvironment.

Cancer cells frequently exhibit defects in DNA damage repair (DDR), leading to genomic instability. Mutations in DDR genes or epigenetic alterations leading to the downregulation of DDR genes can result in increased dependency on other DDR pathways. Therefore, DDR pathways could be a treatment target for various cancers. In fact, polyadenosine diphosphatase ribose polymerase (PARP) inhibitors, such as olaparib (Lynparza®), have shown remarkable therapeutic efficacy against BRCA1/2-mutant cancers through synthetic lethality. Recent genomic analytical advancements have revealed that BRCA1/BRCA2 pathogenic variants are the most frequent mutations among DDR genes in prostate cancer. Currently, the PROfound randomized controlled trial is investigating the efficacy of a PARP inhibitor, olaparib (Lynparza®), in patients with metastatic castration-resistant prostate cancer (mCRPC). The efficacy of the drug is promising, especially in patients with BRCA1/BRCA2 pathogenic variants, even if they are in the advanced stage of the disease. However, olaparib (Lynparza®) is not effective in all BRCA1/2 mutant prostate cancer patients and inactivation of DDR genes elicits genomic instability, leading to alterations in multiple genes, which eventually leads to drug resistance. In this review, we summarize PARP inhibitors' basic and clinical mechanisms of action against prostate cancer cells and discuss their effects on the tumor microenvironment.

Prostate fibroblasts enhance androgen receptor splice variant 7 expression in prostate cancer cells.

BACKGROUND: Androgen receptor splice variant (AR-V) expression has been associated with prostate cancer (PCa) progression to castration-resistant PCa during androgen deprivation therapy, which reduces androgen production and inhibits androgen action in PCa cells. However, the mechanisms whereby aberrant AR-V expression is increased in PCa are still largely unknown. Fibroblasts in tumor stroma influence PCa initiation and aggressiveness, and which may play a crucial role in eliciting genetic changes during malignant transformation in human prostate epithelium. Here, our aim was to determine whether prostate fibroblasts in tumor stroma induce aberrant AR-V7 expression in PCa cells under low androgen concentration. METHODS: We performed in vitro experiments using androgen-sensitive, AR-positive PCa cell lines (LNCaP and 22Rv1 cells), commercially available prostate stromal cells (PrSC), and primary cultured prostate fibroblasts (pcPrF) from PCa specimens collected from biopsies of patients with advanced PCa. PCa cells were cocultured with each of the three fibroblast lines (PrSC, pcPrF-M37, and pcPrF-M48). RESULTS: The proliferation under low androgen concentration of LNCaP and 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48 was significantly increased compared to that of PCa cells cultured alone. Androgen receptor-full length (AR-FL) protein expression was increased in LNCaP and 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48. AR-V7 protein expression was increased in 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48. Under low androgen concentration, AR-V7 protein expression was slightly detected in LNCaP cells cocultured with PrSC or pcPrF-M37. Cytokine array analysis revealed that monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) levels in the conditioned medium of 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48 were increased under low androgen concentration. High IL-8 concentration (30 ng/ml) resulted in significantly increased protein expression of AR-FL, AR-V7, and phospho-NF-κB p65 in 22Rv1 cells. In contrast, IL-8 antibody (1 µg/ml) decreased AR-V7 protein expression in 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48. CONCLUSIONS: pcPrF from PCa specimens increase the expression of aberrant AR-V7 in PCa cells. IL-8 may be a target for preventing the expression of aberrant AR-Vs in PCa.

Real-world effectiveness of nivolumab plus ipilimumab and second-line therapy in Japanese untreated patients with metastatic renal cell carcinoma: 2-year analysis from a multicenter retrospective clinical study (J-cardinal study).

BACKGROUND: Nivolumab plus ipilimumab combination therapy is one of the standard therapies for untreated renal cell carcinoma patients with an International Metastatic Renal Cell Carcinoma Database Consortium intermediate/poor risk. We have previously reported the 1-year analysis results of the effectiveness and safety of nivolumab plus ipilimumab combination therapy in the real-world setting in Japan. Here, we report the effectiveness of nivolumab plus ipilimumab combination therapy and of second-line therapy, using 2-year analysis. METHODS: This retrospective observational study enrolled Japanese patients with previously untreated metastatic renal cell carcinoma who initiated nivolumab plus ipilimumab combination therapy between August 2018 and January 2019. Data were collected from patients' medical records at baseline and at 3 months, 1 year and 2 years after the last enrollment. RESULTS: Of the 45 patients enrolled, 10 patients (22.2%) each had non-clear cell renal cell carcinoma and Eastern Cooperative Oncology Group performance status ≥2 at baseline. Median follow-up period was 24.0 months; objective response rate was 41.5%, with 6 patients achieving complete response; median progression-free survival was 17.8 months and 24-month progression-free survival and overall survival rates were 41.6 and 59.1%, respectively. Second-line therapy achieved an objective response rate of 20%; median progression-free survival was 9.8 months. Median progression-free survival 2 was 26.4 months. CONCLUSIONS: The effectiveness of nivolumab plus ipilimumab combination therapy at 2-year analysis in the real-world setting in Japan was comparable to that reported in CheckMate 214. The current analysis also demonstrated the effectiveness of second-line therapy after nivolumab plus ipilimumab combination therapy.

Clinical Factors Associated With Pathological Grade Group 1 Patients in D'Amico Intermediate-Risk Group Following Robot-Assisted Radical Prostatectomy: A Retrospective Multicenter Cohort Study in Japan (The MSUG94 Group).

INTRODUCTION: We aimed to examine the relationship between D'Amico intermediate-risk and pathological grade group 1 (pGG1) after robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: In this retrospective multicenter cohort study, D'Amico intermediate-risk prostate cancer patients who did not receive neoadjuvant therapy, and underwent RARP at 10 institutions in Japan were examined for preoperative factors associated with pGG1. RESULTS: In total, we enrolled 1161 D'Amico intermediate-risk prostate cancer patients. The pGG1 and pGG ≥2 groups comprised 73 (6.3%), and 1088 (93.7%) cases, respectively. Biochemical recurrence-free survival (BCRFS) of the pGG1 group was equivalent to that of the D'Amico low-risk patients. Among the 3 D'Amico intermediate-risk factors (IRF), the pGG1-rate was 24% with prostate-specific antigen (PSA) of 10 to 20 ng/mL alone, and 30% with cT2b alone. Both groups had significantly higher pGG1-rates than other groups. Down-grading from biopsy GG ≥2 to pGG1 was relatively rare (3.9%). Patients with pGG1 were further stratified by prostate volume (PV) (cutoff, 40 cc) among patients with one IRF and PSA of 10 to 20 ng/mL. Patients with one IRF, PSA of 10 to 20 ng/mL, and PV >40 cc had a relatively good BCRFS similar to that of the D'Amico low-risk group. CONCLUSION: Among intermediate-risk prostate cancer patients, those with pGG1 have a good prognosis. Downgrading from biopsy GG ≥2 is rare, and definitive treatment may be recommended for patients with biopsy GG ≥2. Patients with one IRF, PSA of 10 to 20 ng/mL, and PV >40 cc who are eligible for RARP may be candidates for active surveillance.

A Multicentre Retrospective Study of Nivolumab Plus Ipilimumab for Untreated Metastatic Renal Cell Carcinoma.

BACKGROUND/AIM: To evaluate the effectiveness and safety of nivolumab plus ipilimumab for untreated metastatic renal cell carcinoma in real-world clinical practice in Japan based on 1-year follow-up results. PATIENTS AND METHODS: This multicentre, retrospective study analysed 45 metastatic renal cell carcinoma patients who received nivolumab plus ipilimumab between August 2018 and January 2019 in Japan. Data were extracted from patients' medical records. Subgroup analyses were performed based on baseline demographic data and treatment history. RESULTS: The objective response rate was 42.5% (complete response rate: 10.0%). The 12-month overall survival rate was 81.4% and the progression-free survival rate was 56.1%. Thirty-five patients (77.8%) showed any grade treatment-related adverse events and 17 (37.8%) showed grade ≥3 treatment-related adverse events, with no significant difference in safety between subgroups. CONCLUSION: The effectiveness and safety of nivolumab plus ipilimumab in real-world clinical practice with 1-year follow-up were comparable with those of the CheckMate 214 trial.

Prognostic Effect of Preoperative Psoas Muscle Hounsfield Unit at Radical Cystectomy for Bladder Cancer.

Radical cystectomy (RC) is the standard treatment for patients with advanced bladder cancer. Since RC is a highly invasive procedure, the surgical indications in an aging society must be carefully judged. In recent years, the concept of "frailty" has been attracting attention as a term used to describe fragility due to aging. We focused on the psoas muscle Hounsfield unit (PMHU) and analyzed its appropriateness as a prognostic factor together with other clinical factors in patients after RC. We retrospectively analyzed the preoperative prognostic factors in 177 patients with bladder cancer who underwent RC between 2008 and 2020. Preoperative non-contrast computed tomography axial image at the third lumbar vertebral level was used to measure the mean Hounsfield unit (HU) and cross-sectional area (mm2) of the psoas muscle. Univariate analysis showed significant differences in age, sex, clinical T stage, and PMHU. In multivariate analysis using the Cox proportional hazards model, age (hazard ratio (HR) = 1.734), sex (HR = 2.116), cT stage (HR = 1.665), and PMHU (HR = 1.758) were significant predictors for overall survival. Furthermore, using these four predictors, it was possible to stratify the prognosis of patients after RC. Finally, PMHU was useful as a simple and significant preoperative factor that correlated with prognosis after RC.

A case of adenocarcinoma of the rete testis with durable response to cisplatin-based chemotherapy.

INTRODUCTION: Adenocarcinoma of the rete testis is a rare malignancy with a poor prognosis. We report a case of adenocarcinoma of the rete testis with a durable response to cisplatin-based chemotherapy. CASE PRESENTATION: A 48-year-old man with Down syndrome (trisomy 21) presented with a 1-month history of painless swelling of the left scrotum. The physical examination revealed a left testis with a hydrocele associated with a tumor and enlarged pelvic and para-aortic lymph nodes. He underwent a radical orchiectomy. The specimen was diagnosed as adenocarcinoma of the rete testis. The patient received 7 cycles of chemotherapy (1 cycle of BEP and 6 cycles of EP) postoperatively. The metastatic lymph nodes were reduced in size for at least 12 months. Our patient with adenocarcinoma of the rete testis obtained an acceptable response to cisplatin-based chemotherapy. CONCLUSION: We treated a patient with an adenocarcinoma of the rete testis who had an acceptable response to platinum-based chemotherapy.

[Initial Experience of Photodynamic Diagnosis-Assisted Transurethral Resection of Bladder Tumor (PDD-TURBT)].

Photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) is expected to be useful in preventing oversight of non-muscle-invasive bladder cancer (NMIBC) and in reducing the intravesical recurrence rate after transurethral resection of bladder tumor (TURBT). We report our initial experience with28 cases of PDD-assisted TURBT (122 samples) performed at our hospital from February 2018 to April 2019. The median age of the patients was 74.5 years, and 18 of the 28 were primary cases. Each patient underwent TURBT with oral administration of 5-ALA 20 mg/kg 3 hours before endoscopic examination. The sensitivity was 89.8% when both white light and blue light were used, which was superior to the sensitivity of 67.8% when using only white light (p＜0.01, McNemar's test). Among the first several cases, we experienced high false positivity, which suggested that some experience may be required to discriminate tumors from inflammatory lesions. In fact, the specificity and the positive likelihood ratio improved with experience. No grade 2 or higher adverse events were observed among our cases. The median follow-up period was 738 days, and 9 of 28 patients (32. 1%) had recurrence within the follow-up period. In conclusion, our initial experience with PDD-assisted TURBT demonstrated its excellent diagnostic sensitivity and safety, as previously reported.

[Neoajuvant Chemotherapy with Gemcitabine and Cisplatin Plus S-1 for Primary Female Urethral Adenocarcinoma].

A 67-year-old female presented for evaluation of a left inguinal mass. Contrast-enhanced computed tomography revealed a tumor surrounding the urethra. Magnetic resonance imaging showed that the tumor had invaded the bladder neck on the anterior aspect of the urethra. The serum carbohydrate antigen 19-9 level was elevated. The clinical diagnosis was a primary adenocarcinoma of the female urethra (cT4N2M0). The initial treatment consisted of gemcitabine plus cisplatin (GC) and oral fluoropyrimidine (S-1). A total cysto-urethrectomy with anterior vaginal wall resection, pelvic and inguinal lymphadenectomy, and urinary diversion with ileal conduit formation were performed. The final diagnosis was urethral adenocarcinoma (ypT4ypN2, stage IV). Twelve months post-operatively, there was no evidence of recurrence or distant metastases.

Toward strong self-healing polyisoprene elastomers with dynamic ionic crosslinks.

To compromise high mechanical strength and efficient self-healing capability in an elastomer with dynamic crosslinks, optimization of the molecular structure is crucial in addition to the tuning of the dynamic properties of the crosslinks. Herein, we studied the effects of molecular weight, content of carboxy groups, and neutralization level of ionically crosslinked polyisoprene (PI) elastomers on their morphology, network rearrangement behavior, and self-healing and mechanical properties. In this PI elastomer, nanosized sphere-shaped ionic aggregates are formed by both neutralized and non-neutralized carboxy groups that act as stickers. The number density of the ionic aggregates that act as physical crosslinks increased with increase in the stickers' concentration, although the size of the ionic aggregates was independent of the molecular weight and the stickers' concentration. The ionic network was dynamically rearranged by the stickers' hopping between the ionic aggregates, and the rearrangement was accelerated by decreasing the neutralization level. We found that the 2Rg of the PI must be significantly larger than the average distance between the ionic aggregates to obtain a mechanically strong PI elastomer. We also found that further increase in the molecular weight is effective to enhance the dimensional stability of the elastomer. However, this approach reduced the elastomer's self-healing rate at the same time because the diffusion and randomization of the polymer chains between the damaged faces were reduced. In this work, we clearly demonstrated the principle in the optimization of the molecular structure for the ionically crosslinked PI elastomers to tune the mechanical and autonomous self-healing properties.

[A Case of Extragonadal Germ Cell Tumor Treated by Induction Therapy with A Reduced Bep Regimen].

A 21-year-old man with chief complaints of left hypochondriac and chest pain was shown to have multiple masses in the lung, a pleural effusion in the right cavum thoracis, a mediastinal mass, and lymphadenopathy detected by computed tomographic scan. He was diagnosed with an extragonadal germ cell tumor based on pathologic findings from lung biopsies and elevation of the serum total human chorionic gonadotropin. He underwent a reduced chemotherapy regimen consisting of bleomycin, cisplatin, and etoposide (reduced BEP) to lower the risk of acute respiratory distress syndrome (ARDS), a manifestation of choriocarcinoma syndrome, which occurs at induction chemotherapy with the full-dose BEP regimen. Choriocarcinoma syndrome did not develop during chemotherapy, and he has been disease-free since salvage chemotherapy and subsequent retroperitoneal lymph node dissection.

The usefulness of the maximum Hounsfield units (HU) in predicting the shockwave lithotripsy outcome for ureteral stones and the proposal of novel indicators using the maximum HU.

Computed tomography (CT) attenuation value of ureteral stones is one of the predictors of shockwave lithotripsy (SWL) outcome. It is common to use the mean Hounsfield units (HU) to describe the CT attenuation value. However, an observer bias can occur when measuring the mean HU in the conventional method. On the other hand, our way to obtain only the maximum HU is simpler and less biased. We retrospectively evaluated 464 patients with ureteral stones who underwent SWL and compared predictive accuracy of various factors including maximum and mean HU. Results were determined after a single SWL. Predictors of SWL success were examined by the statistical analysis of successful and failed groups. 324 of the 464 patients who underwent SWL were stone-free after a single SWL. Significant differences were found in factors related to CT attenuation value and stone size. As a result of receiver operating characteristic analysis, it was found that maximum HU and mean HU, major diameter and volume have equivalent prediction accuracy, respectively. Multivariate analysis revealed that maximum HU and major diameter were included in independent predictors. We also examined the new original indicators using maximum HU and major diameter. Stone-resistant probability obtained from the logistic model and Maximum HU and Major diameter Index obtained by multiplying maximum HU by major diameter were useful for predicting SWL success, respectively. In conclusion, maximum HU and mean HU have equivalent predictive accuracy, and maximum HU is easier to measure and less biased than mean HU.

Pre-treatment ratio of periprostatic to subcutaneous fat thickness on MRI is an independent survival predictor in hormone-naïve men with advanced prostate cancer.

BACKGROUND: Epidemiological studies have shown an association between obesity and prostate cancer (PCa) aggressiveness. However, little is known about periprostatic fat (PPF) and its relationship with overall fat deposition in PCa. PPF is thought to contribute to PCa growth and migration via secreted factors and induction of chronic inflammation. We investigated if pre-treatment PPF thickness correlates with overall survival (OS). METHODS: We reviewed 85 hormone-naïve men with advanced PCa who had received androgen deprivation therapy (ADT). PPF thickness was measured by magnetic resonance imaging (MRI) and compared with subcutaneous fat (SCF) thickness as an internal control. Visceral fat (VF) area measured by computed tomography served as an additional control. We evaluated the relationship between laboratory data, pathology results, and obesity parameters and OS. RESULTS: Median follow-up was 50.6 months. Thirty-six patients died during follow-up. Univariate analysis revealed that nadir PSA titer, Gleason score, N stage, M stage, extent of disease by bone scan grade, hemoglobin, lactate dehydrogenase, alkaline phosphatase, and PPF/SCF ratio were associated with OS. Multivariate analysis revealed that nadir PSA titer, N stage, and PPF/SCF ratio were independent prognostic factors for survival. The 5-year OS in the patients with higher PPF/SCF ratio (≥ 1) and lower PPF/SCF ratio (< 1) was 49.5% and 66.5%, respectively (P = 0.039). CONCLUSIONS: Pre-treatment ratio of PPF-to-SCF thickness on MRI is an independent predictor of survival in hormone-naïve men with advanced PCa. This could be useful for predicting which patients are more likely to develop castration-resistant PCa.

Randomized controlled study of the efficacy and safety of continuous saline bladder irrigation after transurethral resection for the treatment of non-muscle-invasive bladder cancer.

OBJECTIVE: To evaluate the efficacy and safety of continuous saline bladder irrigation (CSBI) after transurethral resection of bladder tumour (TURBT) in patients with low- to intermediate-risk non-muscle invasive bladder cancer (NMIBC). PATIENTS AND METHODS: In this prospective randomized study, 250 patients with primary low- to intermediate-risk tumours were enrolled. Patients were randomly allocated to receive CSBI (2 000 mL/h for the first 1 h, then 1 000 mL/h for 2 h, followed by 500 mL/h for 15 h) or a single immediate instillation of mitomycin C (MMC) after TURBT. The primary endpoint was recurrence-free survival, and secondary endpoints were progression-free survival and adverse events. RESULTS: A total of 227 patients (114 in the CSBI group and 113 in MMC group) remained for analysis after exclusion criteria had been applied. The median follow-up period was 37 months. No significant differences in patient characteristics were observed between the groups. The 5-year recurrence-free rates for CSBI and MMC were 62.6% (95% confidence interval [CI] 0.49-0.73) and 70.4% (95% CI 0.59-0.78), respectively. Kaplan-Meier analysis of recurrence-free survival did not show any significant differences between the groups (log-rank test P = 0.53). Furthermore, there were no significant differences between the groups in terms of tumour progression rate and the median time to first recurrence. The incidence of adverse events was significantly lower in the CSBI group. CONCLUSIONS: The results show that CSBI after TURBT may be a treatment option for patients with low- to intermediate-risk NMIBC in terms of its prophylactic effect and safety.

Efficacy of Ethinylestradiol Re-challenge for Metastatic Castration-resistant Prostate Cancer.

BACKGROUND: There has recently been renewed interest in the use of estrogens as a treatment strategy for castration-resistant prostate cancer (CRPC). The purpose of this study was to evaluate the feasibility and efficacy of ethinylestradiol re-challenge (re-EE) in the management of CRPC. PATIENTS AND METHODS: Patients with metastatic CRPC who received re-EE after disease progression on prior EE and other therapy were retrospectively reviewed for prostate-specific antigen (PSA) response, PSA progression-free survival (P-PFS) and adverse events. RESULTS: Thirty-six re-EE treatments were performed for 20 patients. PSA response to the initial EE treatment was observed in 14 (70%) patients. PSA response to re-EE was 33.3% in 36 re-EE treatments. The median P-PFS for patients treated with initial and re-EE was 7 months and 4 months, respectively. Interestingly, PSA response to re-EE was observed even in non-responders to initial EE, and those treated with multiple re-EE. No patients developed cardiovascular or thromboembolic events. CONCLUSION: Re-EE may be safely repeated several times and can lead to a prolonged disease control in selected patients. Re-challenge with EE appears to be a reasonable option worth considering for patients with metastatic CRPC.