Real-world short-term outcomes of prostate urethral lift in Japan: A prospective cohort study.

OBJECTIVES: We report the first prospective trial of prostatic urethral lift for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia in Japan. METHODS: This prospective study was conducted at a single institution and included patients with benign prostatic hyperplasia who underwent prostatic urethral lift based on the Japanese surgical indication. The primary efficacy endpoint was reduced international prostatic symptoms score in the early postoperative period after prostatic urethral lift. To assess efficacy, international prostatic symptoms score, quality of life, sexual health inventory for men, and uroflowmetry were evaluated 2 weeks before, 2 weeks after, and 6 weeks after surgery. RESULTS: We enrolled 120 elderly men. The patients experienced significantly reduced international prostatic symptoms scores from 15 at the baseline to 13 at 2 weeks, and to 10 at 6 weeks, respectively. The peak flow rates did not change significantly at any time point. Three patients had serious adverse events of grade 3a in the Clavien-Dindo classification. Four patients were evaluated for sexual function, and none had ejaculatory dysfunction. CONCLUSION: In the Japanese population, prostatic urethral lift is reliably performed under local anesthesia and rapidly improves symptoms.

Salvage Androgen Deprivation Therapy as Potential Treatment for Recurrence after Robot-Assisted Radical Prostatectomy.

BACKGROUND: The efficacy of intermittent androgen deprivation therapy (ADT) for biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP) is unknown, and its usefulness in Japanese practice needs to be investigated. METHODS: We conducted a retrospective analysis of 85 patients who underwent RARP and were selected for intermittent ADT for postoperative recurrence at Kanazawa University Hospital between 2009 and 2019. Intermittent ADT was administered for 2 years. If prostate-specific antigen levels increased post-treatment, intermittent ADT was reinitiated. The median follow-up period was 47 months. RESULTS: The 73 patients had completed the initial course of ADT, and 12 were under initial ADT. The 5-year castration-resistant prostate-cancer-free survival rates, cancer-specific survival, and overall survival were 92.7%, 98.3%, and 94.7%, respectively. A subgroup analysis of 69 patients who completed intermittent ADT was conducted to evaluate the BCR rate following initial ADT. The 5-year BCR-free survival rate was 53.2%. Multivariate analysis identified testosterone ≤ 0.03 ng/mL during ADT as the sole predictor of BCR after ADT. CONCLUSIONS: Salvage intermittent ADT may be an effective treatment option for BCR after RARP. In addition, it would be useful to confirm strong testosterone suppression as a criterion for transition to intermittent therapy.

Comprehensive analysis of perioperative hypotension in photodynamic diagnosis-assisted transurethral resection of bladder tumor with 5-aminolevulinic acid.

OBJECTIVE: Intraoperative hypotension remains a serious adverse event of photodynamic diagnosis-assisted transurethral resection of bladder tumor with oral administration of 5-aminolevulinic acid. We conducted a re-analysis of perioperative hypotension in photodynamic diagnosis-assisted transurethral resection of the bladder tumor with oral 5-aminolevulinic acid to ascertain its safety. METHODS: A total of 407 cases who underwent transurethral resection of bladder tumors in our institution were reviewed (274 cases for the PDD group with photodynamic diagnosis and 133 for the white light (WL) group without). A classification of hypotension severity was devised to identify risk factors for clinically troublesome hypotension. The distribution of hypotension severity in each of the PDD and WL groups was compared. Additionally, the patient background and perioperative data by hypotension severity were compared only in the PDD group. RESULTS: More patients with moderate and severe hypotension were noted in the PDD group. The renal function was lower with increasing hypotension severity in the PDD group. More patients on general anesthesia were included in the mild and moderate hypotension group, whereas more patients on spinal anesthesia were included in the severe hypotension group. Furthermore, the frequency of side effects other than hypotension tended to increase with hypotension severity. CONCLUSIONS: Renal function impairment and the other adverse effects of 5-aminolevulinic acid may be risk factors for severe hypotension. Mild or moderate hypotension may be caused by general anesthesia and severe hypotension may be caused by spinal anesthesia. To elucidate specific risk factors, further case-control studies are warranted.

A seed link connector protruding into the bladder formed a bladder stone.

Introduction: Low-dose-rate brachytherapy is performed for localized prostate cancer. We report the first case of a bladder stone encompassing the seed migrated into the bladder in a patient treated with low-dose-rate brachytherapy. Case presentation: A man was diagnosed with prostate cancer and underwent low-dose-rate brachytherapy. After 2 months, dysuria occurred, and ultrasonography revealed a needle-shaped high-intensity protruding from the prostate into the bladder. Cystoscopy examination found a seed link connector. With the possibility of natural dissolution of the seed link, careful observation was chosen. However, 16 months later, hematuria occurred, and an X-ray revealed a bladder stone encompassing the seed. Compared with the X-ray right after seeding, the seed located near the right bladder neck had fallen. The seed was removed by transurethral bladder lithotripsy. Conclusion: Seeds should be carefully located within the prostate, otherwise a bladder stone may be formed encompassing the seed.

Procalcitonin in advanced urological cancer-bacterial versus non-bacterial infections: prospective cohort study.

OBJECTIVES: Patients with advanced cancer may develop bacterial infections (BI) as their general condition worsens, but general blood tests often find it difficult to distinguish them from non-bacterial infections (NBI). The present prospective study was undertaken to investigate the effectiveness of serum procalcitonin levels in distinguishing between BI and NBI in patients with advanced urological cancer. METHODS: This study prospectively evaluated patients diagnosed with locally advanced or metastatic or recurrent urological cancer in our department from September 2013 to December 2019. Body temperature was measured in the axilla and the measurement results were recorded. Febrile episodes of ≥38.0°C were analysed, and written patient consent was obtained at the onset of the fever. RESULTS: Of 75 patients enrolled in the present study, 90 febrile episodes were analysed. A total of 34 of 90 febrile episodes were regarded as BI, and the remaining 56 febrile episodes as NBI. The median procalcitonin value was significantly higher in the BI group (p=0.0015), while no significant difference was found between the two groups for white blood cell count and C reactive protein. Additionally, a white blood cell count of less than 1.0×10ˆ9/L resulted in BI in all cases. The procalcitonin receiver operating characteristic area under the curve was 0.710 (95% CI 0.586 to 0.83), excluding cases with white blood cell counts of <1.0 × 103/µL. CONCLUSIONS: Procalcitonin is a rapid and affordable marker for differentiation between BI and NBI in patients with advanced urological cancer.

Does the quality of endoscopic equipment influence the recurrence rate after photodynamic diagnosis-assisted transurethral resection of bladder tumor?

BACKGROUND: Photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) for nonmuscle-invasive bladder cancer is superior to conventional white-light TURBT for cancer detection. However, when performing PDD-TURBT, cystoscopy findings vary depending on the quality of the endoscopic equipment. In this study, we compared the effects of different types of endoscopic equipment on postoperative outcomes. METHODS: Patients who underwent their first PDD-TURBT at our clinic were selected. Patients on whom PDD-TURBT was performed using endoscopic equipment A were sorted into Group A, and patients on whom PDD-TURBT was performed using equipment S were sorted into Group S. The characteristics, recurrence-free survival (RFS), and recurrence frequency of these patients were retrospectively investigated and compared. The prognostic factors for RFS were also analyzed. RESULTS: A total of 49 patients were included in Group A and 46 in Group S. In Group S, a higher detection rate (8.2% vs. 30.4 %, p < 0.01) of carcinoma in situ (CIS) was noted. RFS tended to be better in Group S (HR 0.63, p = 0.15). The frequency of recurrence also tended to be lower in Group S (4.92 vs. 3.66 per 10,000 person-days, p = 0.08). Furthermore, CIS (HR 0.30, p = 0.04) and Bacillus Calmette-Guerin therapy (HR: 0.26, p = 0.01) were significant favorable prognostic factors for RFS. CONCLUSION: The quality of the endoscopic equipment may influence postoperative recurrence after PDD-TURBT. Higher-quality endoscopic instruments have superior CIS detection capabilities, which can lead to improvements in postoperative outcomes with the appropriate selection of postoperative adjuvant therapy.

Bone Turnover Markers, n-Terminal Propeptide of Type I Procollagen and Tartrate-Resistant Acid Phosphatase Type 5b, for Predicting Castration Resistance in Prostate Cancer.

Bone is a common site of prostate cancer metastasis. Bone turnover markers n-terminal propeptide of type I procollagen (P1NP) and tartrate-resistant acid phosphatase type 5b (TRACP-5b) are highly sensitive to bone remodeling activity. However, their prognostic significance as markers of prostate cancer is unknown. This study retrospectively examined the usefulness of P1NP and TRACP-5b as prognostic biomarkers. Castration-resistant prostate cancer recurrence-free survival (CFS) was estimated using the Kaplan-Meier method. A predictive model for CFS was constructed using multivariate analysis. This study enrolled 255 patients diagnosed with prostate cancer at Kanazawa University Hospital. The median follow-up was 115.1 months. Patients with both high serum P1NP and TRACP-5b levels, defined as having a poor bone turnover category (BTC), had significantly shorter CFS. Multivariate analysis identified Gleason score, metastasis, and BTC poor as predictors for castration resistance in prostate cancer. Using these three factors, a prognostic model was established, categorizing patients into low-risk (no or one factor) and high-risk (two or three factors) groups. In the low-risk group, the median CFS was not reached, contrasting with 19.1 months in the high-risk group (hazard ratio, 32.23, p < 0.001). Combining P1NP and TRACP-5b may better predict castration resistance.

Enzalutamide versus Abiraterone Plus Prednisolone for Nonmetastatic Castration-Resistant Prostate Cancer: A Sub-Analysis from the ENABLE Study for PCa.

Enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) can improve the survival of patients with castration-resistant prostate cancer (CRPC). However, the agent that is more effective against nonmetastatic CRPC remains unclear. To evaluate the agent that can be used as the first-line treatment for CRPC, an investigator-initiated, multicenter, randomized controlled trial (ENABLE Study for PCa) including both metastatic and nonmetastatic CRPC was conducted in Japan. The prostate-specific antigen (PSA) response rate, overall survival, some essential survival endpoints, and safety of patients with nonmetastatic CRPC were also analyzed. In this subanalysis, 15 and 26 patients in the ENZ and ABI arms, respectively, presented with nonmetastatic CRPC. There was no significant difference in terms of the PSA response rate between the ENZ and ABI arms (80% and 64%, respectively; p = 0.3048). The overall survival did not significantly differ between the two arms (HR: 0.68; 95% CI: 0.22-2.14, p = 0.5260). No significant differences were observed in terms of radiographic progression-free survival and cancer-specific survival between the ENZ and ABI arms (HR: 0.81; 95% CI: 0.35-1.84; p = 0.6056 and HR: 0.72; 95% CI: 0.19-2.73; p = 0.6443, respectively). Only four and six patients in the ENZ and ABI arms, respectively, had ≥grade 3 adverse events. ABI and ENZ had similar efficacy and safety profiles in patients with nonmetastatic CRPC.

Does radical cystectomy have a better prognosis than bladder conservative treatment in the real world?

PURPOSE: To compare the prognosis and quality of life between radical cystectomy and bladder conservative treatment for muscle invasive bladder cancer in the real world. MATERIALS AND METHODS: Patients treated for muscle invasive bladder cancer without metastases were retrospectively evaluated for overall survival, progression-free survival, and rehospitalization. RESULTS: Of the 141 patients, 62 underwent bladder conservative treatment and 79 underwent radical cystectomy. Patients who underwent radical cystectomy had significantly better progression-free survival (HR: 1.83, 95% CI: 1.12-3.00; p < 0.01) and overall survival (HR: 1.82, 95% CI: 0.99-3.34; p = 0.03) than those who underwent conservative treatment. However, there was no significant difference in prognosis between patients who refused to undergo radical cystectomy and those who underwent. In addition, rehospitalization rates for complications and additional treatment were significantly higher in patients who received conservative treatment (69.3% vs. 34.2%; p < 0.01), and the length of hospital stay was also prolonged compared to patients who received radical cystectomy (26 vs. 9 days; p = 0.03). CONCLUSIONS: Overall, conservative treatment had a significantly poorer prognosis than radical cystectomy, but there was no significant difference in prognosis when comparing patients who refused radical cystectomy and received conservative treatment with those who received radical cystectomy. However, hospitalization rates and length of stay were significantly worse for patients who chose conservative treatment, which may lead to a decline in quality of life.

Identification of uromodulin deposition in the stroma of perinephric fibromyxoid nephrogenic adenoma by mass spectrometry.

Nephrogenic adenoma (NA) is an epithelial lesion that usually occurs in the mucosa of the urinary tract. Rare cases of deep infiltrative or perinephric lesions have also been reported. Recently, NA with characteristic fibromyxoid stroma (fibromyxoid NA) has been proposed as a distinct variant. Although shedding of distal renal tubular cells due to urinary tract rupture has been postulated as the cause of NA in general, the mechanism underlying extraurinary presentation of NA and fibromyxoid stromal change in fibromyxoid NA remains unknown. In this study, we performed mass spectrometry (MS) analysis in a case of perinephric fibromyxoid NA of an 82-year-old man who underwent right nephroureterectomy for distal ureteral cancer. The patient had no prior history of urinary tract injury or radiation. Periodic acid-Schiff staining-positive eosinophilic structureless deposits in the stroma of fibromyxoid NA were microdissected and subjected to liquid chromatography/MS. The analysis revealed the presence of a substantial amount of uromodulin (Tamm-Horsfall protein). The presence of urinary content in the stroma of perinephric fibromyxoid NA suggests that urinary tract rupture and engraftment of renal tubular epithelial cells directly cause the lesion.

A case of condyloma acuminatum of the bladder concurrently diagnosed with urothelial carcinoma.

Introduction: Condyloma acuminatum usually occurs in the external genitalia and rarely in the bladder mucosa. Here, we report a case of condyloma acuminatum of the bladder that was detected concurrently with urothelial carcinoma. Case presentation: A 42-year-old man was referred to our urology department with positive urine cytology for urothelial carcinoma. Cystoscopy revealed a broad-base nonpapillary bladder tumor. The patient underwent a transurethral resection of the bladder tumor. Pathological examination revealed urothelial carcinoma, high-grade pT1, and concurrent resection of condyloma acuminatum. DNA was extracted from the paraffin-embedded transurethral resection of the bladder tumor tissue specimens. HPV11 was detected in condylomas by PCR and in situ hybridization, whereas HPV was not detected in urothelial carcinomas. Conclusion: We report a rare case of condyloma acuminatum of the bladder that was concurrently diagnosed with urothelial carcinoma from the same site.

Role of Positive Biopsy Core Ratio in Prostate Cancer Patients.

BACKGROUND/AIM: The percentage of positive cores (PPC) is increasingly recognized as a prognostic factor in prostate cancer. However, the usefulness of PPC for patients undergoing androgen deprivation therapy (ADT) and high-risk group has not been adequately studied. PATIENTS AND METHODS: A retrospective analysis was conducted of 255 patients who underwent prostate biopsy (all-case group). We examined the efficacy of PPC as a prognostic biomarker. RESULTS: Eighty-nine patients were treated with ADT alone (ADT group), and 107 patients were classified as high-risk (high-risk group). The median duration of follow-up was 112.4 months, 85.3 months, and 110.0 months for the all-case, ADT, and high-risk groups, respectively. Patients with PPC >60% had significantly shorter prostate cancer-specific survival (CSS) and castration-resistant prostate cancer-free survival (CFS) in the all-case and ADT groups. In the high-risk group, patients with PPC >60% had shorter CFS but no difference in CSS. Multivariate analysis showed that significant independent predictors of prostate CSS were the presence of metastasis at diagnosis and PPC >60% in the all-case and ADT groups. CONCLUSION: PPC may be a prognostic factor in ADT treated and high-risk prostate patients.

Efficacy of keishibukuryogan for hot flashes in prostate cancer patients receiving androgen deprivation therapy: a sub-analysis focusing on hormonal and cytokine levels.

Background: The current study attempted to elucidate the mechanisms of keishibukuryogan (TJ-25) efficacy by focusing on hormonal and cytokine levels. This is a sub-analysis of serum hormonal and cytokine levels extracted from the single-arm prospective study. Methods: Twenty-five participants were administrated TJ-25 at a dose of 2.5 g three times daily for 12 weeks, and competed for a diary of their hot flashes conditions. Various hormonal and cytokine values, including interleukin (IL)-8 and tumor necrosis factor-α (TNF-α), were measured at the baseline and 12-week visits. The correlation of hot flashes with hormonal and cytokine levels at baseline was investigated. As part of the responder analyses, all participants were divided into two groups based on the median baseline values of all hormones and cytokines at baseline, and the change amounts in strength and frequency of hot flashes from baseline to 12-week visits in both groups were compared. Furthermore, a correlation in change amounts (Δ values) by TJ-25 administration between hot flashes and each parameter was also conducted. Results: Hot flashes intensity was inversely related to estradiol levels (r=-0.433, P=0.019), and frequency was inversely related to progesterone levels (r=-0.415, P=0.025). In the responder analyses, the effectiveness of TJ-25 for hot flash strength increased in the patients with higher levels of TNF-α at baseline (P=0.0372). TJ-25 was more efficient in frequency in the patients with higher levels of IL-8 (P=0.0312). TJ-25 efficacy, on the other hand, was not significantly associated with changes in any hormonal or cytokine levels between the baseline and 12-week visits. However, ΔIL-8 and ΔTNF-α were not significantly correlated with Δstrength and Δfrequency of hot flashes by TJ-25 administration. Conclusions: Hot flashes were inversely correlated with estradiol and progesterone levels. TJ-25 was more effective in patients with higher TNF-α and IL-8 levels, with no significant change in serum levels caused by the treatment. The suggestive mechanism for the effects of keishibukuryogan is that this drug doesn't suppress the production of IL-8 and TNF-α, but may inhibit some actions of these cytokines.

The CCL2-CCR2 Axis Contributes to Migration of Cabazitaxel-resistant Prostate Cancer Cells.

BACKGROUND/AIM: Developing resistance to cabazitaxel is a major challenge in patients with docetaxel- and castration-resistant prostate cancer (CRPC) since it is frequently administered as a last resort. We have previously reported that CCL2 induces resistance to the antiproliferative effect of cabazitaxel in DU145-TxR/CxR prostate cancer cell lines. However, how CCL2 induces resistance to the antimigration effect of cabazitaxel remains unclear. MATERIALS AND METHODS: We established a cabazitaxel-resistant cell line, DU145-TxR/CxR, from a previously established paclitaxel-resistant cell line, DU145-TxR, which was confirmed to show docetaxel resistance. We performed migration assay and analyzed the expression of epithelial-mesenchymal transition markers using DU145-TxR/CxR with or without CCL2 silencing with small interfering RNA (siRNA) transfection. RESULTS: Cabazitaxel inhibited the migration of DU145 cells through the inactivation of STAT3. A CCR2 (a specific receptor of CCL2) antagonist suppressed the migration of DU145-TxR and DU145-TxR/CxR cells under cabazitaxel treatment. Western blotting revealed that the CCR2 antagonist inhibited STAT3 phosphorylation in DU145-TxR and DU145-TxR/CxR cells under cabazitaxel treatment. CCL2 silencing with siRNA in DU145-TxR and DU145-TxR/CxR cells decreased migration through STAT3 and p38 inactivation. Furthermore, CCL2 activated AKT, and CCR2 antagonist inhibited AKT phosphorylation in DU145-TxR and DU145-TxR/CxR cells with recovery of sensitivity to cabazitaxel under cabazitaxel treatment. CONCLUSION: The CCL2-CCR2 axis is a key contributor to resistance to the antimigration effect of cabazitaxel in prostate cancer cells. CCL2-CCR2 axis inhibition may be a potential therapeutic target against chemoresistant CRPC in combination with cabazitaxel.

Comparison of postoperative urinary continence and incontinence types between conventional and Retzius-sparing robot-assisted radical prostatectomy.

AIMS: This study aimed to investigate the postoperative urinary continence rate and incontinence types compared over time between conventional robot-assisted radical prostatectomy (C-RARP) and Retzius-sparing RARP (RS-RARP). METHODS: All 61 cases were selected from the C-RARP and RS-RARP by propensity score matching, and the pad scale, 24-h pad weight test, and International consultation on incontinence questionnaire-short form (ICIQ-SF) were followed-up over time up to 12 months. RESULTS: The probability of urinary continence per pad scale evaluation differed according to how it was defined: the continence rate 12 months after C-RARP and RS-RARP were 94% and 95% for 1 pad/day, 85% and 92% for 1 security pad/day, 61% and 85% for no pad use, respectively, which were all significantly better with RS-RARP. The results of the 24-h pad weight test were significantly better with RS-RARP at both 3 and 12 months, with median C-RARP versus RS-RARP values of 5 versus 1 g and 2 versus 0 g, respectively. In terms of types of urinary incontinence, the rates of postoperative stress urinary incontinence (SUI) increased in both procedures but to a lesser extent in RS-RARP. Other types of urinary incontinence, such as urge incontinence and terminal dribbling, did not differ significantly before and after surgery and between the two procedures. CONCLUSIONS: Postoperative urinary continence was better with RS-RARP than with C-RARP per all follow-up parameters until 12 months postoperatively. Postoperative SUI was significantly lower with RS-RARP than with C-RARP, which was considered the main reason for better postoperative urinary continence with RS-RARP.

Intravesical BCG therapy with photodynamic diagnosis-guided transurethral resection of bladder tumors improves recurrence-free survival.

BACKGROUND: Intravesical Bacille Calmette-Guerin (BCG) therapy has been reported to be effective in preventing recurrence and progression in non-muscle invasive bladder cancer. Furthermore, photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) improves the accuracy of cancer diagnosis and contributes to lower recurrence rates. The purpose of this study is to investigate whether more tumor resection with PDD-TURBT rather than conventional TURBT before BCG therapy outweighs the benefit of BCG therapy alone. METHODS: Patients who underwent intravesical BCG therapy following TURBT in our institution from 2010 to 2021 were included. They were divided into the following two groups: those who received PDD-TURBT before BCG treatment (PDD + BCG group) and those who received conventional TURBT before BCG treatment (WL + BCG group). The 2-year recurrence-free survival (RFS) and progression-free survival (PFS) of the two groups were retrospectively analyzed and compared. RESULTS: The 2-year RFS was significantly improved in the PDD + BCG group (hazard ratio [HR]: 2.41, 95% confidence interval [CI]: 1.26-4.60; p = 0.025). No significant difference in 2-year PFS was noted between the two groups. Analysis of prognostic factors for RFS showed that PDD-TURBT w We think that this text does not adequately express the meaning that we want to deliver to the reader.as a significant prognostic factor in univariate analysis (HR: 0.41, 95% CI: 0.18-0.92; p = 0.03). CONCLUSION: BCG treatment following PDD-TURBT significantly improved RFS more than BCG therapy following WL-TURBT. More accurate tumor localization and more efficient tumor resection by PDD-TURBT may have a positive impact on subsequent BCG treatments even if the treatment is administered postoperatively.

Postoperative functional and cancer control evaluation of conventional and Retzius-sparing robot-assisted radical prostatectomy: Comparison of selected cases by propensity score matching.

AIM: Although many reports have shown that Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) is effective for postoperative urinary continence, the postoperative voiding status and sexual function associated with this technique have not yet been adequately compared with those associated with conventional RARP (C-RARP). In this study, the lower urinary tract function, erectile function, and cancer control after C-RARP and RS-RARP were compared chronologically. MATERIALS AND METHODS: We selected 50 cases of C-RARP and RS-RARP each by propensity score matching and evaluated them over time using various questionnaires. Urinary continence recovery rates and biochemical recurrence (BCR)-free survival rates were calculated using the Kaplan-Meier method and compared between the two groups using the log-rank test. RESULTS: When urinary continence was defined as 0 pads per day, 0 pads per day + 1 security linear, or ≤1 pad per day, the postoperative improvement in urinary continence was better with RS-RARP over the course of up to 1 year for all definitions. The International Consultation on Incontinence Questionnaire-Short Form total scores and the Overactive Bladder Symptom Scores were better in the postoperative RS-RARP group. There were no significant differences in the International Prostate Symptom Score total score, QOL score, and erectile hardness score between the two groups during the observation period. The BCR-free survival did not differ significantly between the two groups CONCLUSIONS: Postoperative urinary continence was better in the RS-RARP group than in the C-RARP group; however, the voiding function, erectile function, and cancer control did not differ significantly.

Is it Necessary to Treat all Metastatic Prostate Cancer With Upfront Androgen Receptor Axis-targeted Agents?

BACKGROUND/AIM: In recent years, initial treatment for patients with high-risk metastatic castration-sensitive (mCS) prostate cancer (PC) has been shifting from vintage hormone therapy to upfront androgen receptor axis-targeted agents (ARAT), but the proportion of Asian patients enrolled in clinical trials investigating the effectiveness of ARAT use is low. We examined the outcomes of Japanese patients with mCSPC who received ARAT as second-line therapy or afterwards. PATIENTS AND METHODS: Among the PC patients receiving treatment at Kanazawa University Hospital from 2000 to 2019, 190 patients with mCSPC were enrolled in the study. Their characteristics and prognosis were retrospectively investigated. RESULTS: All patients received androgen deprivation therapy (ADT) as initial treatment. A total of 142 (74.3%) of 190 patients had progression to castration-resistant PC (CRPC), of whom 77 (54.2%) received ARAT as second-line therapy or afterwards. The median overall survival (OS) of CRPC patients was 70.57 months and the median OS from CRPC was 44.88 months. The median OS of LATITUDE high-risk patients that used ARAT after the second-line treatment was 56.15 months, which was significantly longer than that of patients who did not use ARAT (hazard ratio=0.68, 95% confidence interval=0.40-1.15; p=0.0089). CONCLUSION: The prognosis of LATITUDE high-risk patients with CRPC selected for initial ADT therapy had a good prognosis compared to findings in other studies. These results suggest that there is a possibility that a certain number of patients with LATITUDE high-risk may have good prognosis even if only conventional ADT is performed and ARAT is used after CRPC.

Prevalence of Human Papillomavirus Types 16/18 and Effect of Vaccination among Japanese Female General Citizens in the Vaccine Crisis Era.

The Japanese government withdrew its recommendation for human papillomavirus (HPV) vaccination in June 2013 and resumed it in April 2022. This period is known as the vaccine crisis in Japan. This study aimed to elucidate the prevalence and genotype distribution of HPV among Japanese female citizens, and the effect of vaccination against HPV-16/18 in the era of the vaccine crisis. We recruited Japanese female citizens and asked them to provide self-collected samples from the vaginal wall using cotton swabs for HPV genotyping. Furthermore, we collected the participants' characteristics, including lifestyle and experience of vaccination against HPV, to determine the significant association with HPV infection. HPV-16/18 positivity was found in 5.6% (115/2044) of participants. The highest vaccination rate was observed in the age group of 20-24 years (60.6%), whereas the lowest HPV-16/18 positivity was observed in the age group of 45-49 years (2.8%), followed by the age group of 20-24 years (4.0%). Experience with HPV vaccination significantly reduced the risk of HPV-16/18 infection (adjusted odds ratio, 0.047; 95% confidence interval, 0.011-0.196). Vaccinated women were much less likely to be infected by HPV-16/18, regardless of the HPV vaccine type or the vaccination dose.

Suppression of androgen receptor signaling induces prostate cancer migration via activation of the CCL20-CCR6 axis.

The suppression of androgen receptor (AR) expression exacerbates the migration potential of prostate cancer. This study identified a previously unrecognized regulation of the AR-controlled pathway that promotes migration potential in prostate cancer cells. Prostate cancer cells that pass through a transwell membrane (mig cells) have a higher migration potential with a decreased AR expression than parental cells. In this study, we aimed to elucidate the mechanism of migration enhancement associated with the suppression of AR signaling. Expression of C-C motif ligand 20 (CCL20) is upregulated in mig cells, unlike in the parental cells. Knockdown of AR with small interfering RNA (siAR) in LNCaP and C4-2B cells increased CCL20 secretion and enhanced the migration of cancer cells. Mig cells, CCL20-treated cells, and siAR cells promoted cell migration with an enhancement of AKT phosphorylation and Snail expression, while the addition of a C-C chemokine receptor 6 (CCR6, the specific receptor of CCL20) inhibitor, anti-CCL20 antibody, and AKT inhibitor suppressed the activation of AKT and Snail. With 59 samples of prostate cancer tissue, CCL20 secretion was profuse in metastatic cases despite low AR expression levels. Snail expression was associated with the expression of CCL20 and CCR6. A xenograft study showed that the anti-CCL20 antibody significantly inhibited Snail expression, thereby suggesting a new therapeutic approach for castration-resistant prostate cancer with the inhibition of the axis between CCL20 and CCR6.