Practice Patterns of Korean Urologists Regarding Positive Surgical Margins after Radical Prostatectomy: a Survey and Narrative Review.

BACKGROUND: There is no clear consensus on the optimal treatment with curative intent for patients with positive surgical margins (PSMs) following radical prostatectomy (RP). The aim of this study was to investigate the perceptions and treatment patterns of Korean urologists regarding the resection margin after RP. METHODS: A preliminary questionnaire was prepared by analyzing various studies on resection margins after RP. Eight experienced urologists finalized the 10-item questionnaire. In July 2019, the final questionnaire was delivered via e-mail to 105 urologists in Korea who specialize in urinary cancers. RESULTS: We received replies from 91 of the 105 urologists (86.7%) in our sample population. Among them, 41 respondents (45.1%) had performed more than 300 RPs and 22 (24.2%) had completed 500 or more RPs. In the question about whether they usually performed an additional biopsy beyond the main specimen, to get information about surgical margin invasion during surgery, the main opinion was that if no residual cancer was suspected, it was not performed (74.7%). For PSMs, the Gleason score of the positive site (49.5%) was judged to be a more important prognostic factor than the margin location (18.7%), multifocality (14.3%), or margin length (17.6%). In cases with PSMs after surgery, the prevailing opinion on follow-up was to measure and monitor prostate-specific antigen (PSA) levels rather than to begin immediate treatment (68.1%). Many respondents said that they considered postoperative radiologic examinations when PSA was elevated (72.2%), rather than regularly (24.4%). When patients had PSMs without extracapsular extension (pT2R1) or a negative surgical margin with extracapsular extension (pT3aR0), the response 'does not make a difference in treatment policy' prevailed at 65.9%. Even in patients at high risk of PSMs on preoperative radiologic screening, 84.6% of the respondents said that they did not perform neoadjuvant androgen deprivation therapy. Most respondents (75.8%) indicated that they avoided nerve-sparing RP in cases with a high risk of PSMs, but 25.7% said that they had tried nerve-sparing surgery. Additional analyses showed that urologists who had performed 300 or more prostatectomies tended to attempt more nerve-sparing procedures in patients with a high risk of PSMs than less experienced surgeons (36.6% vs. 14.0%; P = 0.012). CONCLUSION: The most common response was to monitor PSA levels without recommending any additional treatment when PSMs were found after RP. Through this questionnaire, we found that the perceptions and treatment patterns of Korean urologists differed considerably according to RP resection margin status. Refined research and standard practice guidelines are needed.

Radical prostatectomy for clinically localized prostate cancer in patients aged 75 years or older: comparison with primary androgen deprivation therapy.

OBJECTIVE: To determine whether radical prostatetomy (RP) is suitable for prostate cancer patients with age ≥75 years in comparison to primary androgen deprivation therapy (PADT). PATIENTS AND METHODS: A cohort study was conducted in clinically localized prostate cancer patients with ≥75 years of age who underwent RP or PADT at six institutions from 2005 to 2013. Patients who had less than 12 months of follow-up, or received neoadjuvant or adjuvant therapy were excluded. We compared clinical characteristics, cancer-specific and overall survivals, and post-treatment complication rates between two groups. RESULTS: We included 92 and 99 patients in the RP and PADT groups, respectively. In survival analyses, there were no significant differences in cancer-specific and overall survivals (p = .302 and .995, respectively). The incidence of serious adverse events (cardio- or cerebrovascular event, or bone fracture) was higher in the PADT group (p = .001). Multivariable analysis showed that PADT had a worse effect on the serious adverse events (OR 10.12, p = .038). CONCLUSIONS: In selected elderly patients, RP was safe and effective for treatment of localized prostate cancer, as compared to PADT. Surgical treatment options should be considered in elderly patients with respect to life expectancy, rather than chronological age.

Efficacy and Safety of Desmopressin Add-On Therapy for Men with Persistent Nocturia on α-Blocker Monotherapy for Lower Urinary Tract Symptoms: A Randomized, Double-Blind, Placebo Controlled Study.

PURPOSE: We investigated the efficacy and safety of desmopressin add-on therapy for men with persistent nocturia on α-blocker for lower urinary tract symptoms in this placebo controlled study. MATERIALS AND METHODS: The study included men 40 to 65 years old with lower urinary tract symptoms and persistent nocturia despite α-blocker therapy for at least 8 weeks. Patients were randomized to once daily placebo or desmopressin 0.2 mg for 8 weeks. The primary end point was to assess changes in the mean number of nocturia episodes from baseline to the final assessment. Other secondary end points and adverse events were evaluated. RESULTS AND LIMITATION: A total of 86 patients were randomized to treatment, including placebo in 39 and desmopressin 0.2 mg in 47. Baseline characteristics were similar in the 2 groups. The desmopressin add-on group was significantly superior to placebo in terms of the change from baseline in the mean number of nocturia episodes (-1.13 ± 0.92 vs -0.68 ± 0.79, p = 0.034), the changes in nocturnal urine volume (p <0.001), total I-PSS (International Prostate Symptom Score) (p = 0.041), the nocturnal polyuria index (p = 0.001) and ICIQ-N (International Consultation on Incontinence Questionnaire-Nocturia) (p = 0.001), and the willingness to continue (p = 0.025). The incidence of adverse events in the desmopressin add-on group was similar to that in the placebo group. Most adverse events were mild. CONCLUSION: Desmopressin add-on therapy in men 40 to 65 years old with persistent nocturia on α-blocker monotherapy for lower urinary tract symptoms is effective and well tolerated.

Radical Prostatectomy in Korean Men Aged 75-Years or Older: Safety and Efficacy in Comparison with Patients Aged 65-69 Years.

Prostate cancer is the most common type of male cancer worldwide. Although radical prostatectomy (RP) is advised for prostate cancer in patients with a life expectancy of more than 10 years by various guidelines, most elderly men still do not undergo the procedure regardless of increasing life expectancy. This study aimed to determine whether RP is suitable for patients with prostate cancer aged 75 years or older. A retrospective study of patients who underwent RP at 6 institutions between 2005 and 2012 was conducted. Patients were divided into 2 groups at the time of surgery: 65-69 years (younger group) and 75 years or older (older group). We compared clinical characteristics, pathological results, complication rates, and recurrence-free survival between the two groups. Compared with the younger group, the older group had significantly higher preoperative serum prostate-specific antigen level, pre- and postoperative Eastern Cooperative Oncology Group (ECOG) performance status grade, hypertension prevalence, and Gleason score at biopsy and RP. However, except urinary incontinence, there were no statistically significant differences in the peri- and post-operative complications. After median follow-up periods of 36 months (younger group) and 40 months (older group), the biochemical recurrence-free survival rates were not significantly different (P = 0.581). Although the urinary incontinence rate was higher in the older group, RP was a suitable option for selected Korean men aged 75 years or older with limited complication rates and excellent outcomes similar to those for patients aged 65-69 years.

Analysis of distress in patients undergoing radical prostatectomy: A multicenter prospective study.

PURPOSE: To analyze the degree of psychological distress experienced pre- and postoperatively in patients who underwent radical prostatectomy after being diagnosed with prostate cancer. MATERIALS AND METHODS: Patients diagnosed with prostate cancer who underwent radical prostatectomy without history of psychiatric disorders were included in this study. The degree of psychological distress was evaluated using hospital anxiety and depression scale (HADS) and distress thermometer (DT) questionnaires preoperatively and at 1, 3, 6, and 12 months postoperatively. RESULTS: Distress was high preoperatively and decreased over the entire period. In addition, HADS-anxiety and HADS-depression scores showed an improved severity, shifting from an abnormal state to a borderline state in some patients. However, the DT score, including emotional problems, spiritual concerns, physical problems, family problems, and practical problems, was slightly higher at 1 month postoperatively compared to preoperatively. Furthermore, even at 12 months postoperatively, about one fifth of patients surveyed had a DT score of 4 or higher, requiring psychiatric intervention. CONCLUSIONS: Before and after radical prostatectomy, a significant number of patients complained of distress such as anxiety, depression, and insomnia, and they needed help from a specialist because of psychological distress even 12 months postoperatively. Therefore, a close evaluation of the patient's psychological distress and supportive treatment are needed during the entire pre- and postoperative period.

Pathophysiology of Overactive Bladder and Pharmacologic Treatments Including ß3-Adrenoceptor Agonists -Basic Research Perspectives.

Overactive bladder (OAB) is a symptom-based syndrome defined by urinary urgency, frequency, and nocturia with or without urge incontinence. The causative pathology is diverse; including bladder outlet obstruction (BOO), bladder ischemia, aging, metabolic syndrome, psychological stress, affective disorder, urinary microbiome, localized and systemic inflammatory responses, etc. Several hypotheses have been suggested as mechanisms of OAB generation; among them, neurogenic, myogenic, and urothelial mechanisms are well-known hypotheses. Also, a series of local signals called autonomous myogenic contraction, micromotion, or afferent noises, which can occur during bladder filling, may be induced by the leak of acetylcholine (ACh) or urothelial release of adenosine triphosphate (ATP). They can be transmitted to the central nervous system through afferent fibers to trigger coordinated urgency-related detrusor contractions. Antimuscarinics, commonly known to induce smooth muscle relaxation by competitive blockage of muscarinic receptors in the parasympathetic postganglionic nerve, have a minimal effect on detrusor contraction within therapeutic doses. In fact, they have a predominant role in preventing signals in the afferent nerve transmission process. ß3-adrenergic receptor (AR) agonists inhibit afferent signals by predominant inhibition of mechanosensitive Aδ-fibers in the normal bladder. However, in pathologic conditions such as spinal cord injury, it seems to inhibit capsaicin-sensitive C-fibers. Particularly, mirabegron, a ß3-agonist, prevents ACh release in the BOO-induced detrusor overactivity model by parasympathetic prejunctional mechanisms. A recent study also revealed that vibegron may have 2 mechanisms of action: inhibition of ACh from cholinergic efferent nerves in the detrusor and afferent inhibition via urothelial ß3-AR.

Second-Line Surgical Management After Midurethral Sling Failure.

Currently, the midurethral sling (MUS) is widely used as a standard treatment in patients with stress urinary incontinence (SUI). Several studies have reported the failure rate of MUS to be approximately 5%-20%. In general, sling failure can be defined as persistent SUI after surgery or a temporary improvement in incontinence followed by recurrence. Failure is also often considered to include cases requiring secondary surgery due to mesh exposure, postoperative voiding difficulty, de novo urgency/urge incontinence, and severe postoperative pain. Because of the lack of large-scale, high-quality research on this topic, no clear guidelines exist for second-line management. To date, transurethral bulking agent injections, tape shortening, repeat MUS, pubovaginal sling (PVS) using autologous fascia, and Burch colposuspension are available options for second-line surgery. Repeat MUS is the most widely used second-line surgical method at present. Bulking agent injections have lower durability and efficacy than other treatments. Tape shortening demonstrates a relatively low success rate, but comparable outcomes if the period from first treatment to relapse is short. In patients with intrinsic sphincter deficiency, PVS and retropubic (RP) MUS can be considered first as second-line management because of their higher success rate than other treatments. When revision or reoperation is required due to prior mesh-related complications, PVS or colposuspension, which is performed without a synthetic mesh, is appropriate for second-line surgery. For patients with detrusor underactivity, a readjustable sling can be a better option because of the high risk of postoperative voiding dysfunction in PVS or RP slings.

RNA interference mediated suppression of TRPV6 inhibits the progression of prostate cancer in vitro by modulating cathepsin B and MMP9 expression.

PURPOSE: The transient receptor potential vanilloid 6 (TRPV6) channel is overexpressed in prostate cancer and its silencing is known to inhibit the growth of LNCaP cells. However, the role of TRPV6 in the metastasis of prostate cancer cells and its relationship to the invasive markers, matrix metalloproteinase (MMP) and cathepsin B, is unclear. Thus, the present study was focused on understanding these tumor-related processes. MATERIALS AND METHODS: We performed a wound-healing assay and a Transwell migration and invasion assay to assess the migration and invasion of prostate cancer cells. Western blot analysis was used to measure the expression of cathepsin B, MMP2, and MMP9. RESULTS: TRPV6 siRNA significantly inhibited the proliferation of LNCaP prostate cancer cells. It also significantly attenuated the wound healing and migration capacities of LNCaP cells. Moreover, the invasiveness of LNCaP cells and the expression of MMP9 and cathepsin B in LNCaP cells were also significantly inhibited by TRPV6 siRNA. CONCLUSIONS: The results indicate that TRPV6 may promote prostate cancer progression in association with MMP9 and cathepsin B, thereby validating further research into TRPV6 as a useful therapeutic target for local invasion or metastasis of advanced prostate cancer.

Clinical guidelines for interstitial cystitis and hypersensitive bladder syndrome.

A clinical guideline and algorism for interstitial cystitis and hypersensitive bladder syndrome has been developed by a group of East Asian urologists as a revised form of the Japanese guideline for interstitial cystitis. The guideline defines interstitial cystitis (IC) as a disease of the urinary bladder diagnosed by 3 requirements; 1) a characteristic complex of lower urinary tract symptoms, 2) bladder pathology such as Hunner's ulcer and bladder bleeding after overdistension, and 3) exclusions of confusable diseases. The characteristic symptom complex is termed as hypersensitive bladder syndrome (HBS), which is defined as bladder hypersensitivity, usually associated with urinary frequency, with or without bladder pain. For the definite diagnosis of IC, cytoscopy or hydrodistension is crutial; HBS is the diagnosis when IC is suspected but not confirmed by the 3 requirements. Numerous therapeutic options are available; however, most of them lack in high level of evidence, leaving a few as recommended therapies. Etiology of IC are multifactorial; the interaction among nervous, immune and endocrine factors forms a vicious cycle, provocating and maintaining inflammatory reactions in the bladder. The inclusion and efficacy criteria for clinical trials should be standardized to enhance the clinical research for this disabling disease, which has proved to be more prevalent than previously believed.

Synaptic connectivity of urinary bladder afferents in the rat superficial dorsal horn and spinal parasympathetic nucleus.

That visceral sensory afferents are functionally distinct from their somatic analogues has been known for a long time but the detailed knowledge of their synaptic connections and neurotransmitters at the first relay nucleus in the spinal cord has been limited. To provide information on these topics, we investigated the synapses and neurotransmitters of identified afferents from the urinary bladder to the superficial laminae of the rat spinal dorsal horn (DH) and the spinal parasympathetic nucleus (SPN) by tracing with horseradish peroxidase, quantitative electron microscopical analysis, and immunogold staining for GABA and glycine. In the DH, most bladder afferent boutons formed synapses with 1-2 postsynaptic dendrites, whereas in the SPN, close to a half of them formed synapses with 3-8 postsynaptic dendrites. The number of postsynaptic dendrites and dendritic spines per bladder afferent bouton, both measures of synaptic divergence and of potential for synaptic plasticity at a single bouton level, were significantly higher in the SPN than in the DH. Bladder afferent boutons frequently received inhibitory axoaxonic synapses from presynaptic endings in the DH but rarely in the SPN. The presynaptic endings were GABA- and/or glycine-immunopositive. The bouton volume, mitochondrial volume, and active zone area, all determinants of synaptic strength, of the bladder afferent boutons were positively correlated with the number of postsynaptic dendrites. These findings suggest that visceral sensory information conveyed via the urinary bladder afferents is processed differently in the DH than in the SPN, and differently from the way somatosensory information is processed in the spinal cord.

Generic and disease-specific health-related quality of life in women with coital incontinence: a prospective, multicenter study.

OBJECTIVE: This study was carried out to evaluate the impact of coital incontinence on health-related quality of life (HRQOL) in women with lower urinary tract symptoms. METHODS: A total of 180 women with sexual activity were evaluated. To obtain HRQOL assessments, patients were asked to fill out the Bristol Female Lower Urinary Tract Symptoms and the Medical Outcomes Study Short Form (SF-36) questionnaires. RESULTS: The coital incontinence group had more frequently symptoms including urgency, urge incontinence, bladder pain, stress incontinence, unpredictable incontinence, nocturnal incontinence, reduced stream, and stopping flow than the no coital incontinence group. The frequency of incontinence and volume of leakage were also higher in the coital incontinence group than the no coital incontinence group. All symptom questions regarding sexual matters and quality of life except cutting down on fluid were more frequent in patients with coital incontinence than those without coital incontinence. Of the eight domains in the SF-36 questionnaire, five domains, namely, Physical functioning, Role-physical functioning, Social functioning, Role-emotional functioning, and Mental health were significantly different between the two groups. When comparing the Bristol Female Lower Urinary Tract Symptoms scores in the two groups, the scores in all domains except Voiding symptoms in the coital incontinence group were significantly higher than those in the no coital incontinence group. Patients with coital incontinence had more HRQOL impairment than those without coital incontinence. CONCLUSIONS: Our study reveals that more emphasis should be placed on coital incontinence in the terminology of urinary incontinence.

Change of sexual function after midurethral sling procedure for stress urinary incontinence.

OBJECTIVES: To compare sexual function in women before and after the midurethral sling procedure for stress urinary incontinence (SUI). METHODS: A total of 75 women undergoing surgery for SUI between September 2005 and September 2006 were recruited for this study. Those who completed the Female Sexual Function Index (FSFI) preoperatively and 6 months postoperatively were included in the analysis. The FSFI is a validated, 19-item questionnaire, which assesses six domains of sexual function, including desire, arousal, lubrication, orgasm, satisfaction, and pain. RESULTS: Data were analyzed for 47 patients. Overall sexual function after the midurethral sling procedure was not significantly different. There were no significant differences in overall sexual function or any of the individual FSFI domain scores between patients with and without concomitant posterior colporrhaphy. There were no significant differences in sexual function between the transobturator and the retropubic surgical routes. CONCLUSIONS: There is no significant change in overall sexual function in women undergoing the midurethral sling procedure. Posterior colporrhaphy and operative methods do not affect overall sexual function.

Health-related quality of life and sexual function in women with stress urinary incontinence and overactive bladder.

BACKGROUND: We evaluated the impact of stress urinary incontinence (SUI) and overactive bladder (OAB) on health-related quality of life (HRQOL) and sexual function. METHODS: A total of 245 women (SUI; n = 123 and OAB; n = 122) from 21 to 79 years old (mean 50.4) were included in the primary analyses. To obtain HRQOL and sexual function assessments, patients were asked to fill in the 'Bristol Female Lower Urinary Tract Symptoms (BFLUTS)' and the 'Medical Outcomes Study Short Form (SF-36)' questionnaires. RESULTS: Of the eight domains in the SF-36 questionnaire, only 'general health' was significantly different between the groups. Patients with SUI had a better general health than those with OAB (P = 0.016). When comparing the BFLUTS scores in the two groups, the score for 'BFLUTS-filling symptoms' was higher in the OAB group (P = 0.002) but that for 'BFLUTS-incontinence symptoms' was higher in the SUI group (P < 0.001). The score for 'BFLUTS-sex' was higher in the SUI group than in the OAB group but this was not statistically significant (P = 0.096). Of the 169 patients who had a sex life, the SUI group had experienced pain (P = 0.033) and leakage (P = 0.056) more frequently during intercourse than the OAB group. CONCLUSION: Both SUI and OAB have a detrimental impact on patient HRQOL in Korean women. In addition, our findings suggest that women with SUI had more frequently experienced pain during intercourse and coital incontinence than those with OAB.

Doxazosin-induced clusterin expression and apoptosis in prostate cancer cells.

The purpose of this study was to correlate temporal expression of clusterin and apoptosis in androgen-independent human prostate cancer cells (PC-3) treated with 25 microM doxazosin. DNA fragmentation, reverse transcriptase polymerase chain reaction, and terminal transferase-mediated biotinylated 16-desoxy-uridene triphosphate nick-end labeling (TUNEL) assays were used to assess degree of apoptosis and temporal and spatial expression of clusterin mRNA and protein. DNA fragmentation was significant at 48 hours. Clusterin mRNA expression was 3-fold higher than control at 9 hours and was maintained over 48 hours. The TUNEL assay showed increasing percentage of apoptotic cells and presence of clusterin after doxazosin treatment. During doxazosin-induced apoptosis in PC3 cells, clusterin appeared to initially accumulate in the cytoplasm and protect against apoptosis; later, after its transport to the nucleus, clusterin was no longer able to suppress apoptosis.

Incidence and risk factors of recurrence of overactive bladder symptoms after discontinuation of successful medical treatment.

PURPOSE: To identify incidence and risk factors of recurrence after discontinuation of successful antimuscarinic therapy in patients with overactive bladder (OAB). MATERIALS AND METHODS: This was a prospective, multicenter trial. Patients who had antimuscarinic agents for more than 12 weeks and showed successful response were enrolled. Successful response was defined as answering 'benefit' for patient perception of treatment benefit and answer lesser than 3 points in patient's perception of bladder condition (PPBC). The enrolled patients discontinued the antimuscarinics, and we evaluated their recurrence with PPBC and OAB symptom score (OABSS) at 1, 3, 6, and 12 months. Primary purpose was to identify the recurrence rate and secondary purpose was to reveal risk factors. RESULTS: Four hundred forty-one patients enrolled and 371 patients completed 6-month follow-up. The enrolled patients showed 1.6 points in PPBC, 2.9 points in OABSS and 1.4 points in IPSS (quality of life) which represented successful response after using antimuscarinics. The cumulative rates of recurrence were 25.6%, 42.3%, and 52.2% at 1, 3, 6 months, respectively. Among 177 patients who did not show recurrence at 6 months, 41 patients were followed up and 4 patients of the 41 patients (9.7%) showed recurrence at 12 months. On univariate and multivariate analyses of recurrence, OAB wet was the risk factor for recurrence after 6 months of discontinuation. CONCLUSIONS: Discontinuation of antimuscarinic therapy after successful treatment resulted in high recurrence rate with time and OAB wet was the independent risk factor for recurrence.

17Beta-Estradiol Inhibits Calcium-Activated Potassium Channel Expressions in Rat Whole Bladder.

PURPOSE: To investigate the effect of estrogen on the expression of calcium-activated potassium (KCa) channels in an overactive bladder rat model. To this end, mRNA and protein levels of KCa channel subtypes in the bladder of ovariectomized rats were measured by reverse transcription polymerase chain reaction and western blotting, respectively. METHODS: Ten-week-old female Sprague-Dawley rats were divided randomly into 3 groups: sham-operated control group (n=11), ovariectomy group (n=11), and the group treated with estrogen after ovariectomy (n=12). Rats in the last group were subcutaneously injected with 17ß-estradiol (50 µg/kg) every other day for 2 weeks, whereas rats in the other 2 groups received vehicle (soybean oil) alone. Two weeks after treatment, the whole bladder was excised for mRNA and protein measurements. RESULTS: Protein levels of the large-conductance KCa (BK) channels in the ovariectomy group were 1.5 folds higher than those in the sham-operated control group. However, the protein levels of the other KCa channel subtypes did not change significantly upon bilateral ovariectomy. Treatment with 17ß-estradiol after ovariectomy restored BK channel protein levels to the control value. In contrast, BK channel mRNA levels were not significantly affected by either ovariectomy alone or 17ß-estradiol treatment. The small-conductance KCa type 3 channel (SK3) mRNA and protein levels decreased to 75% of control levels upon 17ß-estradiol treatment. CONCLUSIONS: These results suggest that 17ß-estradiol may influence urinary bladder function by modulating BK and SK3 channel expression.

A 12-Week, Open Label, Multi-Center Study to Evaluate the Clinical Efficacy and Safety of Silodosin on Voiding Dysfunction in Patients with Neurogenic Bladder.

OBJECTIVES: The purpose of this study is to evaluate clinical effect and safety of α1A -adrenoceptor blocker, silodosin, in patients with voiding dysfunction caused by neurogenic bladder. METHODS: From April 2011 to January 2012, patients who were diagnosed as potential voiding dysfunction associated with neurogenic bladder, aged ≥ 20 years were enrolled. Silodosin (8 mg/day) was administered once daily in the morning with food. The efficacy was assessed at the baseline and after 12 weeks of the treatment having following parameters of international prostate symptom score and other measures including the maximum flow rate and the postvoid residual urine volume. RESULTS: A total of 97 patients were screened and 95 were enrolled. Of these 95 patients, 82 patients were completed and included in analysis. After 12-weeks of treatment, mean total international prostate symptom score decreased significantly from 22.23 ± 6.80 to 14.98 ± 9.48 (P = 0.0002). Voiding symptoms and storage symptoms were also improved by decreasing in international prostate symptom score-QoL from 4.62 ± 0.92 to 3.48 ± 1.63 (P < 0.0001). Maximum flow rate increased significantly from 10.72 ± 2.66 to 15.14 ± 6.63 (P < 0.0001). The main adverse event was ejaculation disorder. No serious adverse events related to silodosin were noted. CONCLUSIONS: This study indicates that silodosin was significantly effective, well tolerated and safe in patients who have voiding dysfunction associated with neurogenic bladder.

Pathological upgrading in prostate cancer patients eligible for active surveillance: Does prostate-specific antigen density matter?

PURPOSE: To evaluate prospectively the role of prostate-specific antigen (PSA) density in predicting Gleason score upgrading in prostate cancer patients eligible for active surveillance (T1/T2, biopsy Gleason score≤6, PSA≤10 ng/mL, and ≤2 positive biopsy cores). MATERIALS AND METHODS: Between January 2010 and November 2013, among patients who underwent greater than 10-core transrectal ultrasound-guided biopsy, 60 patients eligible for active surveillance underwent radical prostatectomy. By use of the modified Gleason criteria, the tumor grade of the surgical specimens was examined and compared with the biopsy results. RESULTS: Tumor upgrading occurred in 24 patients (40.0%). Extracapsular disease and positive surgical margins were found in 6 patients (10.0%) and 8 patients (17.30%), respectively. A statistically significant correlation between PSA density and postoperative upgrading was found (p=0.030); this was in contrast with the other studied parameters, which failed to reach significance, including PSA, prostate volume, number of biopsy cores, and number of positive cores. Tumor upgrading was also highly associated with extracapsular cancer extension (p=0.000). The estimated optimal cutoff value of PSA density was 0.13 ng/mL(2), obtained by receiver operating characteristic analysis (area under the curve=0.66; p=0.020; 95% confidence interval, 0.53-0.78). CONCLUSIONS: PSA density is a strong predictor of Gleason score upgrading after radical prostatectomy in patients eligible for active surveillance. Because tumor upgrading increases the potential for postoperative pathological adverse findings and prognosis, PSA density should be considered when treating and consulting patients eligible for active surveillance.

A comparative study on the efficacy of solifenacin succinate in patients with urinary frequency with or without urgency.

OBJECTIVES: Patients with overactive bladder (OAB) often have trouble perceiving urgency because of difficulties in distinguishing between urgency and desire to void. Empirical antimuscarinic treatment of patients with frequency only may be reasonable if conservative management has failed. We compared the efficacy of solifenacin in patients with frequency with or without urgency. MATERIALS AND METHODS: This multicenter, 12-week, open-label, comparative, non-inferiority clinical trial assessed whether the solifenacin efficacy for frequency without urgency is non-inferior to its efficacy for frequency with urgency. All patients had micturition frequency ≥ 8 voids/day with or without urgency. Primary efficacy variable: daily frequency change at 12 weeks relative to baseline. Secondary efficacy variables: change at 12 weeks relative to baseline in Patients' Perception of Bladder Condition (PPBC), OAB Symptom Score (OABSS), and Benefit, Satisfaction, Willingness to continue (BSW) questionnaire. RESULTS: Of the 286 enrolled patients, 240 (83.9%) completed the study (without urgency n = 115; with urgency n = 125). Full dataset analysis revealed that the groups without and with urgency exhibited significant reductions in daily micturition frequency of -2.49 ± 0.35 (mean ± standard error) and -2.63 ± 0.37, respectively. The lower limit of the 95% two-sided CI of the comparison of the two group means was -1.14, which is smaller than the -0.8 margin of clinical equivalence. The two groups did not differ in improvement in PPBC, OABSS, or BSW scores. Both tolerated the treatment well. CONCLUSIONS: It was not possible to verify that the solifenacin efficacy for frequency alone was non-inferior to its efficacy for OAB. Nevertheless, solifenacin tended to be effective for frequency regardless of urgency. TRIAL REGISTRATION: ClinicalTrials.gov NCT00979472.

Factors associated with continuing medical therapy after transurethral resection of prostate.

OBJECTIVE: To report the clinical characteristics of patients who have persistent lower urinary tract symptoms (LUTS) after surgery for benign prostatic hyperplasia (BPH) and continue their medical therapy postoperatively. MATERIALS AND METHODS: We retrospectively studied 372 patients who underwent transurethral resection of prostate for LUTS/BPH in 8 institutions to determine the differences between patients who continued LUTS/BPH medications for >3 months after surgery and those who did not. Preoperative, intraoperative, and postoperative clinical parameters were assessed. The Student t test and chi square test were used to compare each parameter between patient groups. Multivariate logistic regression analysis was performed to identify risk factors for persistent LUTS and continuing medical therapy after surgery. RESULTS: There were 205 patients (55.1%) who continued their LUTS/BPH medications for >3 months postoperatively. They reported poorer International Prostate Symptom Scores and uroflowmetry results after surgery. Multivariate analysis showed that age >70 years (odds ratio [OR], 2.474; P = .001), history of diabetes (OR, 1.949; P = .040), history of cerebrovascular accident (OR, 5.932; P = .001), any previous LUTS/BPH medication use (OR, 5.384; P = <0.001), and previous antimuscarinic drug use (OR, 2.962; P = .016) were significantly associated with symptom persistency and continuing medical therapy. CONCLUSION: Many patients have persistent voiding dysfunction after surgical treatment for LUTS/BPH. Older age, history of diabetes, history of cerebrovascular accidents, and preoperative antimuscarinic drug uses are possible risk factors.