Improved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer.

BACKGROUND: Patients with prostate cancer who have high-risk biochemical recurrence have an increased risk of progression. The efficacy and safety of enzalutamide plus androgen-deprivation therapy and enzalutamide monotherapy, as compared with androgen-deprivation therapy alone, are unknown. METHODS: In this phase 3 trial, we enrolled patients with prostate cancer who had high-risk biochemical recurrence with a prostate-specific antigen doubling time of 9 months or less. Patients were randomly assigned, in a 1:1:1 ratio, to receive enzalutamide (160 mg) daily plus leuprolide every 12 weeks (combination group), placebo plus leuprolide (leuprolide-alone group), or enzalutamide monotherapy (monotherapy group). The primary end point was metastasis-free survival, as assessed by blinded independent central review, in the combination group as compared with the leuprolide-alone group. A key secondary end point was metastasis-free survival in the monotherapy group as compared with the leuprolide-alone group. Other secondary end points were patient-reported outcomes and safety. RESULTS: A total of 1068 patients underwent randomization: 355 were assigned to the combination group, 358 to the leuprolide-alone group, and 355 to the monotherapy group. The patients were followed for a median of 60.7 months. At 5 years, metastasis-free survival was 87.3% (95% confidence interval [CI], 83.0 to 90.6) in the combination group, 71.4% (95% CI, 65.7 to 76.3) in the leuprolide-alone group, and 80.0% (95% CI, 75.0 to 84.1) in the monotherapy group. With respect to metastasis-free survival, enzalutamide plus leuprolide was superior to leuprolide alone (hazard ratio for metastasis or death, 0.42; 95% CI, 0.30 to 0.61; P<0.001); enzalutamide monotherapy was also superior to leuprolide alone (hazard ratio for metastasis or death, 0.63; 95% CI, 0.46 to 0.87; P = 0.005). No new safety signals were observed, with no substantial between-group differences in quality-of-life measures. CONCLUSIONS: In patients with prostate cancer with high-risk biochemical recurrence, enzalutamide plus leuprolide was superior to leuprolide alone with respect to metastasis-free survival; enzalutamide monotherapy was also superior to leuprolide alone. The safety profile of enzalutamide was consistent with that shown in previous clinical studies, with no apparent detrimental effect on quality of life. (Funded by Pfizer and Astellas Pharma; EMBARK ClinicalTrials.gov number, NCT02319837.).

Association Between Sarcopenia and Survival of Patients with Organ-Confined Renal Cell Carcinoma after Radical Nephrectomy.

BACKGROUND: We aimed to describe the effect of preoperative sarcopenia on oncologic outcomes of organ-confined renal cell carcinoma (RCC) after radical nephrectomy. PATIENTS AND METHODS: A total of 632 patients with pT1-2 RCC who underwent radical nephrectomy between 2004 and 2014 were retrospectively analyzed. From preoperative computerized tomography (CT) scans, skeletal muscle index (SMI) was measured and gender-specific cutoff values at third lumbar vertebra of 52.4 cm2/m2 for men and 38.5 cm2/m2 for women were used to define sarcopenia. Survivals were compared and associations with sarcopenia were analyzed using Kaplan-Meier log rank tests and Cox proportional hazard regression models. Median follow-up was 83 months. RESULTS: Of 632 patients, 268 (42.4%) were classified as sarcopenic. The sarcopenic group was more advanced in age (57 versus 53 years) and more predominantly male (71.3% versus 59.9%). Sarcopenic patients had lower body mass index (BMI, 23.0 versus 25.9 kg/m2), but there was no difference in tumor size, stage, or nuclear grade. Sarcopenia was associated with poorer overall survival (OS) and cancer-specific survival (CSS; OS 94.0% versus 82.1%; p < 0.001 and CSS 97.5% versus 91.8%; p < 0.001). On multivariate analysis, sarcopenia was an independent risk factor for all-cause mortality [hazard ratio (HR) 2.58; 95% CI 1.02-6.54] and cancer-specific mortality (HR 3.07; 95% CI 1.38-6.83). CONCLUSIONS: Sarcopenia at diagnosis was an independent risk factor for all-cause and cancer-specific mortality after radical nephrectomy for pT1-2 RCC. These findings underscore the importance of assessing presence of sarcopenia for risk stratification even among surgical candidates.

Comparative oncological outcomes after radical prostatectomy or external beam radiation therapy plus androgen deprivation therapy in men with clinical T3b prostate cancer.

OBJECTIVE: To compare oncological outcomes in men with clinical T3b prostate cancer who underwent radical prostatectomy or a combination of radiation therapy plus androgen deprivation therapy. METHODS: Men with clinical T3b prostate cancer who underwent radical prostatectomy or radiation therapy plus androgen deprivation therapy between 2007 and 2014 were evaluated. All patients were relatively healthy, with Eastern Cooperative Oncology Group performance status of 0 or 1 without nodal or distant metastasis. Cancer-specific survival was analyzed. Age, Charlson Comorbidity Index, biopsy Gleason score and pretreatment prostate-specific antigen were adjusted by propensity score matching. The Cox proportional hazards model was used to assess factors prognostic of cancer-specific survival. RESULTS: Of the 152 patients with clinical T3b prostate cancer, 45 underwent radical prostatectomy, and 107 underwent radiation therapy plus androgen deprivation therapy between 2007 and 2014. The mean cancer-specific survival was significantly longer in the radical prostatectomy than in the radiation therapy plus androgen deprivation therapy group (P = 0.029). Age, Charlson Comorbidity Index and pretreatment prostate-specific antigen were significantly higher in the radiation therapy plus androgen deprivation therapy group. In the propensity score matched population of 24 patients each, the median cancer-specific survival remained significantly longer in the radical prostatectomy than in the radiation therapy plus androgen deprivation therapy group (not reached vs 112.93 ± 11.94 months, P = 0.026). Multivariate analysis showed that undergoing radiation therapy plus androgen deprivation therapy was the only significant poor prognostic factor for cancer-specific survival (hazard ratio 6.694, 95% confidence interval 1.642-27.592, P = 0.008). CONCLUSION: Cancer-specific survival was significantly longer in men with clinical T3b prostate cancer who underwent radical prostatectomy than radiation therapy plus androgen deprivation therapy, suggesting that radical prostatectomy can be a better treatment option for the initial definitive treatment for these patients.

The Regenerative Effects of c-Met Agonistic Antibodies in Vocal Fold Atrophy.

BACKGROUND: Atrophy of the vocal folds and the accompanying glottic insufficiency affect the quality of life. Although growth factors have been used to treat muscle atrophy, their effectiveness is limited by their short half-life. METHODS: In total, 15 rabbits and 24 rats were used for the study. The right recurrent laryngeal nerves of all animals were transected. One month following nerve transection, PBS (PBS group), rHGF (HGF group), or a c-Met agonistic antibody (c-Met group) was injected into the paralyzed vocal folds. The larynges of the rabbits were harvested from each group for histologic examination and subjected to PCR analysis. RESULTS: Cross-sectional areas (CSAs) of thyroarytenoid muscles were evaluated. The c-Met group had increased CSAs compared to the PBS and HGF groups, but there were no significant differences compared to normal controls. The expression levels of myogenesis-related genes were evaluated three weeks after the injection. The expression levels of myosin heavy chain IIa were significantly increased in the PBS group, while the expression levels of MyoD were increased in the c-Met group. CONCLUSIONS: The c-Met agonistic antibody showed promise for promoting muscle regeneration in a vocal fold palsy model.

Safety of autologous bone marrow-derived mesenchymal stem cells in erectile dysfunction: an open-label phase 1 clinical trial.

BACKGROUND AIMS: The efficacy of phosphodiesterase type 5 inhibitors (PDE5Is), which are commonly used to treat erectile dysfunction (ED), is not satisfactory in patients with denervation of the cavernous nerve due to pelvic surgeries and diabetes mellitus (DM). Pre-clinical studies using bone marrow-derived mesenchymal stem cells (BMSCs) to treat ED have shown promising results. The authors conducted a phase 1 clinical trial with autologous BMSCs in patients with ED due to radical prostatectomy or DM. METHODS: Ten patients (five with post-prostatectomy ED and five with DM-associated ED) who could not perform sexual activity despite taking the maximum dose of a PDE5I were enrolled. The brief clinical trial protocol was registered with the US National Institutes of Health on ClinicalTrials.gov (NCT02344849). The primary outcome was the safety of stem cell therapy, and the secondary outcome was the improvement of erectile function. RESULTS: Of the 13 patients screened, 10 were registered in the clinical trial and received autologous BMSCs and nine completed the clinical trial. One patient with post-prostatectomy ED experienced two treatment-emergent adverse events (TEAEs) (pyrexia and back pain), and two patients with DM-associated ED experienced a total of five TEAEs (one case each of viral upper respiratory tract infection, prostatitis and pruritus and two cases of hyperglycemia). Of these patients, one with DM-associated ED experienced two serious TEAEs (two instances of hyperglycemia). All TEAEs were considered not to be related to autologous BMSC therapy. In addition, no clinical significance was identified related to other safety measures, such as laboratory tests and vital signs. The mean International Index of Erectile Function score increased significantly at 1 month versus baseline (24.9 versus 18.1, P = 0.0222). CONCLUSIONS: This phase 1 clinical trial confirmed the safety and potential efficacy of autologous BMSC therapy in patients with ED. The authors' results need to be confirmed by a phase 2 clinical trial.

Pharmacological inhibition of androgen receptor expression induces cell death in prostate cancer cells.

The androgen receptor (AR) plays an important role in the pathogenesis and development of prostate cancer (PCa). Mostly, PCa progresses to androgen-independent PCa, which has activated AR signaling from androgen-dependent PCa. Thus, inhibition of AR signaling may be an important therapeutic target in androgen-dependent and castration-resistant PCa. In this study, we determined the anticancer effect of a newly found natural compound, sakurasosaponin (S-saponin), using androgen-dependent and castration-resistant PCa cell lines. S-saponin induces mitochondrial-mediated cell death in both androgen-dependent (LNCaP) and castration-resistant (22Rv1 and C4-2) PCa cells, via AR expression. S-saponin treatment induces a decrease in AR expression in a time- and dose-dependent manner and a potent decrease in the expression of its target genes, including prostate-specific antigen (PSA), transmembrane protease, serin 2 (TMPRSS2), and NK3 homeobox 1 (NKX3.1). Furthermore, S-saponin treatment decreases B-cell lymphoma-extra large (Bcl-xL) and mitochondrial membrane potential, thereby increasing the release of cytochrome c into the cytosol. Moreover, Bcl-xL inhibition and subsequent mitochondria-mediated cell death caused by S-saponin were reversed by Bcl-xL or AR overexpression. Interestingly, S-saponin-mediated cell death was significantly reduced by a reactive oxygen species (ROS) scavenger, N-acetylcystein. Animal xenograft experiments showed that S-saponin treatment significantly reduced tumor growth of AR-positive 22Rv1 xenografts but not AR-negative PC-3 xenografts. Taken together, for the first time, our results revealed that S-saponin induces mitochondrial-mediated cell death in androgen-dependent and castration-resistant cells through regulation of AR mechanisms, including downregulation of Bcl-xL expression and induction of ROS stress by decreasing mitochondrial membrane potential.

Hybrid ileal pouch with concomitant anti-refluxing and refluxing ureteroileal anastomosis.

PURPOSE: We report our preliminary experience of using a hybrid ileal pouch, assessing oncologic outcomes, complications, voiding, and renal function. METHODS: The study included 25 patients with bladder cancer treated with radical cystectomy with a hybrid ileal pouch with concomitant anti-refluxing and refluxing anastomosis, performed by a single surgeon. The patients were divided into two groups (first and last cases) according to the surgery date. Postoperative complications, separate renal function by renal scan, voiding function by uroflowmetry with residual urine, and oncologic outcomes were assessed. RESULTS: The surgery duration was shorter in the last cases than the first cases. The voiding volume increased with time. There were 23 cases of grade 3 complication in 12 patients and one case of grade 4 complication (sepsis). In the first cases, ureterovesical stenosis occurred in five cases, whereas in the last cases, there were no cases of stenosis. In separate renal function, there was no difference between the left and right side or between the first and last cases. CONCLUSIONS: The hybrid ileal pouch showed acceptable oncologic and functional outcomes and complications; therefore, it can be used according to the appropriate surgical situation with a relatively short bowel segment during neobladder construction.

United in Fight against prOstate cancer (UFO) registry: first results from a large, multi-centre, prospective, longitudinal cohort study of advanced prostate cancer in Asia.

OBJECTIVES: To document the management of advanced prostate cancer including diagnosis, prognosis, treatment, and care, in real-world practice in Asia using the United in Fight against prOstate cancer (UFO) registry. PATIENTS AND METHODS: We established a multi-national, longitudinal, observational registry of patients with prostate cancer presenting to participating tertiary care hospitals in eight Asian countries. A total of 3636 eligible patients with existing or newly diagnosed high-risk localised prostate cancer (HRL), non-metastatic biochemically recurrent prostate cancer (M0), or metastatic prostate cancer (M1), were consecutively enrolled and are being followed-up for 5 years. Patient history, demographic and disease characteristics, treatment and treatment decisions, were collected at first prostate cancer diagnosis and at enrolment. Patient-reported quality of life was prospectively assessed using the European Quality of Life-five Dimensions, five Levels (EQ-5D-5L) and Functional Assessment of Cancer Therapy for Prostate Cancer questionnaires. In the present study, we report the first interim analysis of 2063 patients enrolled from study start (15 September 2015) until 18 May 2017. RESULTS: Of the 2063 enrolled patients, 357 (17%), 378 (19%), and 1328 (64%) had HRL, M0 or M1 prostate cancer, respectively. The mean age at first diagnosis was similar in each group, 56% of all patients had extracapsular extension of their tumour, 28% had regional lymph node metastasis, and 53% had distant metastases. At enrolment, 62% of patients had at least one co-morbidity (mainly cardiovascular disease or diabetes), 91.8% of M1 patients had an Eastern Cooperative Oncology Group performance score of <2 and the mean EQ-5D-5L visual analogue score was 74.6-79.6 across cohorts. Treatment of M1 patients was primarily with combined androgen blockade (58%) or androgen-deprivation therapy (either orchidectomy or luteinising hormone-releasing hormone analogues) (32%). Decisions to start therapy were mainly driven by treatment guidelines and disease progression. Decision to discontinue therapy was most often due to disease progression (hormonal drug therapy) or completion of therapy (chemotherapy). CONCLUSION: In the UFO registry of advanced prostate cancer in Asia, regional differences exist in prostate cancer treatment patterns that will be explored more deeply during the follow-up period; prospective follow-up is ongoing. The UFO registry will provide valuable descriptive data on current disease characteristics and treatment landscape amongst patients with prostate cancer in Asia.

Surgical details and renal function change after robot-assisted partial nephrectomy.

OBJECTIVES: To investigate whether differences in surgical details during robot-assisted partial nephrectomy impact postoperative renal function. METHODS: Patient, tumor and perioperative characteristics of 751 patients who underwent robot-assisted partial nephrectomy were analyzed with respect to the difference in ipsilateral glomerular filtration rate measured by diethylenetetramine pentaacetic acid renal scan. Detailed surgical methods defined for tumor excision (cutting vs splitting), hemostasis (suturing vs clipping) and renorrhaphy (continuous vs interrupted) were analyzed for early glomerular filtration rate decline and long-term recovery. RESULTS: The glomerular filtration rate of the entire cohort decreased by 9.8 mL/min/1.73 m2 (22%) at 3 months postoperatively, gradually increasing thereafter. The recovery slope was 1.7 mL/min/1.73 m2 /year during a median follow-up period of 23.0 months. Early glomerular filtration rate decline was more pronounced in the cutting group (23.5 vs 20.1%, P = 0.009). Clipping was associated with less glomerular filtration rate decline throughout the observation period, and the recovery slope was also significantly higher (2.7 vs 1.1 mL/min/1.73 m2 /year). In multivariate analysis, early decline was associated with age, preoperative glomerular filtration rate, parenchymal volume loss and ischemia >25 min. With respect to long-term recovery, suturing had the greatest adverse impact (ß = -5.060, P < 0.0001, 95% confidence interval -7.709, -2.411) in addition to parenchymal volume reduction and early decline. In the propensity-matched cohort accounting for differences in tumor size and complexity, suturing was persistently associated with a significant glomerular filtration rate decline until >2 years after surgery. CONCLUSIONS: Hemostatic sutures during robot-assisted partial nephrectomy might interfere with long-term renal function recovery irrespective of parameters that determine the initial function change. As the splitting method reduces the use of sutures, modifying these details might help preserve renal function.

Association of Muscle Mass with Survival after Radical Prostatectomy in Patients with Prostate Cancer.

PURPOSE: Although muscle mass has been associated with survival in patients with various types of solid tumors, the relationship between muscle mass and survival in patients with prostate cancer remains unclear. We retrospectively investigated the association of muscle mass with survival after radical prostatectomy in patients with prostate cancer. MATERIALS AND METHODS: We reviewed the records of 2,042 patients who underwent radical prostatectomy of prostate cancer between 1998 and 2013. Muscle mass was evaluated by measuring the psoas muscle index on preoperative computerized tomography images. RESULTS: In the lowest, second, third and highest psoas muscle index quartiles the 10-year distant metastasis-free survival rate was 72.5%, 83.8%, 92.3% and 93.7% (p <0.001), the 10-year cancer specific survival rate was 85.7%, 92.1%, 96.8% and 97.6%, and the 10-year overall survival rate was 74.5%, 79.6%, 89.8% and 90.6%, respectively (each p <0.001). The psoas muscle index positively correlated with the body mass index, serum concentrations of IGFBP-3 and bioavailable testosterone, and inversely correlated with patient age, the serum SHBG concentration and the neutrophil-to-lymphocyte ratio. On multivariable analysis the psoas muscle index was independently associated with increased risks of biochemical recurrence, distant metastasis, and cancer specific and overall death. CONCLUSIONS: Low muscle mass may be associated with increased risks of recurrence and mortality in patients who undergo radical prostatectomy of prostate cancer regardless of the body mass index. Large-scale prospective studies are warranted.

Correction to: A novel histone deacetylase inhibitor, CG200745, potentiates anticancer effect of docetaxel in prostate cancer via decreasing Mcl-1 and Bcl-XL.

The blots of control and docetaxel for caspase-9, caspase-3, caspase-8, Bcl-XL, and tubulin in the Figure 4f were reused from Figure 4 of our previous paper published in Journal of Urology in 2010 ( https://doi.org/10.1016/j.juro.2010.07.035 ).

Is Primary Androgen Deprivation Therapy a Suitable Option for Asian Patients With Prostate Cancer Compared With Radical Prostatectomy?

BACKGROUND: We conducted a comparative survival analysis between primary androgen deprivation therapy (PADT) and radical prostatectomy (RP) based on nationwide Korean population data that included all patients with prostate cancer. MATERIALS AND METHODS: This study enrolled 4,538 patients with prostate cancer from the National Health Insurance Service (NHIS) database linked with Korean Central Cancer Registry data who were treated with PADT or RP between January 1, 2007, and December 31, 2014. Kaplan-Meier and multivariate survival analyses stratified by stage (localized and locally advanced) and age (<75 and ≥75 years) were performed using a Cox proportional hazards model to evaluate treatment effects. RESULTS: Among 18,403 patients from the NHIS database diagnosed with prostate cancer during the study period, 4,538 satisfied inclusion criteria and were included in the analyses. Of these, 3,136 and 1,402 patients underwent RP or received PADT, respectively. Risk of death was significantly increased for patients who received PADT compared with those who underwent RP in the propensity score-matched cohort. In subgroup analyses stratified by stage and age, in every subgroup, patients who received PADT had a significantly increased risk of death compared with those who underwent RP. In particular, a much greater risk was observed for patients with locally advanced prostate cancer. CONCLUSIONS: Based on a nationwide survival analysis of nonmetastatic prostate cancer, this study provides valuable clinical implications that favor RP over PDAT for treatment of Asian populations. However, the possibility that survival differences have been overestimated due to not accounting for potential confounding characteristics must be considered.

Percutaneous Obliteration of Urinary Leakage after Partial Nephrectomy Using N-Butyl-Cyanoacrylate Obliteration of the Urinoma with or without Coil Embolization of the Fistula Tract.

PURPOSE: To retrospectively evaluate the safety and efficacy of the percutaneous obliteration of urinary leakage after partial nephrectomy (PN) using coils and N-butyl-cyanoacrylate (NBCA). MATERIALS AND METHODS: Data of 10 consecutive patients who underwent percutaneous obliteration of urinary leakage after PN using coil and NBCA between February 2016 and May 2018 were retrospectively reviewed. A urinary fistulography was performed via the drainage catheter. If the fistulous tract was clearly visualized, super-selective embolization of the fistulous tract with coils and urinoma cavity sealing with NBCA was performed. In cases where the fistulous tract could not be clearly visualized, only urinoma cavity sealing was performed. Outcomes and complications were assessed by reviewing medical records and computed tomography (CT). RESULTS: In 7 (70%) patients who showed obvious urinary fistulous tract, coil embolization of the urinary fistulous tract, followed by sealing of the urinoma cavity with NBCA, was performed. Obliteration of the urinoma without coil embolization of the fistula tract was performed in 3 patients (30%) in whom a distinct fistulous tract could not be visualized. The median number of treatment sessions required to achieve clinical success was 1 (range, 1-5). Four patients underwent multiple repeated procedure with successful results. All patients showed gradual decrease in size or complete disappearance of urinoma on follow-up CT without evidence of urinary leakage during the follow-up period (mean, 44.6 weeks; range, 11-117 weeks). There were no procedure-related complications. CONCLUSIONS: Percutaneous obliteration of urinary leakage after PN using coils and NBCA is safe and effective.

Robot-assisted partial nephrectomy is associated with early recovery of renal function: Comparison of open, laparoscopic, and robot-assisted partial nephrectomy using DTPA renal scintigraphy.

OBJECTIVES: To compare the functional outcomes of open, laparoscopic, and robot-assisted partial nephrectomy (OPN, LPN, and RAPN, respectively) using diethylene triamine penta-acetic acid (DTPA). METHODS: We identified 610 patients who underwent partial nephrectomy for renal cell carcinoma (285 open partial nephrectomy [OPN], 96 laparoscopic partial nephrectomy [LPN], and 229 robot-assisted partial nephrectomy [RAPN]) with preoperative and postoperative DTPA within 1 year. We excluded multiple renal masses and history of immunotherapy or chemotherapy. Predictive factors for glomerular filtration rate (GFR) reduction were assessed using multivariate linear regression. RESULTS: Postoperative complications and disease-free survival were similar in the three groups. Within 1 postoperative year, OPN showed a significantly lower mean ipsilateral GFR than LPN and RAPN (28.9 versus 32.4 versus 32.7 mL/min/1.73 m 2 , respectively; P < 0.001). RAPN was associated with a significantly higher total GFR than OPN within 1 year (76.6 versus 71.2 mL/min/1.73 m 2 , respectively; P = 0.001). On multivariate analysis within 1 year, operation type (OPN versus RAPN: ß = 2.82; 95% confidence interval, 1.17-4.48; P = 0.001) was significantly associated with GFR reduction. CONCLUSION: There was no difference in postoperative complications and disease-free survival among operation types. RAPN could help to promote earlier recovery of ipsilateral GFR than OPN.

Report of the forth Asian Prostate Cancer (A-CaP) study meeting.

The Asian Prostate Cancer (A-CaP) Study is an Asia-wide prospective registry study for surveying the treatment outcome of prostate cancer patients who have received a histopathological diagnosis. The study aims to clarify the clinical situation for prostate cancer in Asia and use the outcomes for the purposes of international comparison. Following the first meeting in Tokyo on December 2015, the second meeting in Seoul, Korea 2016, the third meeting in Chiang Mai, Thailand, on October 2017, the fourth meeting was held in Seoul, again on August 2018 with the participation of members and collaborators from 13 countries and regions. In the meeting, participating countries and regions presented the current status of data collection and the A-CaP office presented a preliminary analysis of the registered cases received from each country and region. Participants discussed ongoing challenges relating to data cleaning and data up-dating which is the next step of the A-CaP study following the data collection phase between 2016 and 2018. There was specific difference in term of the patient characteristics, and initial treatment pattern among East Asia, Southeast Asia and Turkey, and Jordan. Finally, a close relationship between prevalence of PSA test and disease stage of the patients at diagnosis in Japan and Malaysia was discussed.

Time to biochemical relapse after radical prostatectomy and efficacy of salvage radiotherapy in patients with prostate cancer.

BACKGROUND: To investigate the prognostic and therapeutic implications of time to biochemical relapse (BCR) in patients with prostate cancer after radical prostatectomy. METHODS: The records of 3210 consecutive men with prostate cancer who underwent radical prostatectomy between January 1998 and June 2013 were retrospectively reviewed. Patients with BCR were divided into three groups based on quartiles of time to BCR, namely an early group (first quartile), an intermediate group (second and third quartiles) and late group (fourth quartile). RESULTS: 817 (25.5%) patients experienced BCR at a median of 24.9 months after surgery. The 8-year rate of distant metastasis-free survival (64.3% vs. 41.3%, p = 0.002) and cancer-specific survival (86.6% vs. 63.4%, p < 0.001) was higher in the salvage radiotherapy (SRT) group than the androgen deprivation therapy (ADT) group in patients with early BCR, whereas those rates (91.3% vs. 87.9%, p = 0.607 and 100.0% vs. 93.1%, p = 0.144, respectively) were similar in patients with late BCR. In the intermediate BCR group, the impact of SRT over ADT on 8-year cancer-specific survival was modest (91.9% vs. 82.3%, p = 0.057) and was limited to patients with pT2 or pT3a disease. CONCLUSIONS: SRT may decrease the risk of distant metastasis and cancer-specific mortality in patients with early BCR. However, a survival benefit for those with late BCR was not apparent. For patients with intermediate BCR, SRT was associated with a cancer-specific survival benefit in patients with pT2 or pT3a disease. Novel genomic tests and imaging modalities may support clinical decision-making in these patients.

Simple risk assessment in prostate cancer patients treated with primary androgen deprivation therapy: The Korean Cancer Study of the Prostate risk classification.

OBJECTIVES: To investigate the progression to castration-resistant prostate cancer after primary androgen deprivation therapy, and to build a simple risk prediction model for primary androgen deprivation therapy patients based on the Japan Cancer of the Prostate Risk Assessment criteria. METHODS: A total of 602 patients who received primary androgen deprivation therapy were entered into the Korean Cancer Study of the Prostate database. The effect of prognostic factors was determined by multivariate analysis. For each patient, the weight of all factors was totaled to give Korean Cancer Study-prostate scores; patients were divided into three risk groups according to their score. The probability of castration-resistant prostate cancer, cancer-specific survival and overall survival was estimated by Kaplan-Meier analysis. RESULTS: On multivariate analysis for castration-resistant prostate cancer, the significant variables were initial prostate-specific antigen (>40 ng/mL; 1 point), biopsy Gleason score (≥9; 1 point), clinical N1 (1 point), and non-regional lymph node (1 point), bone (1 point) and visceral (1 point) metastasis. The Korean Cancer Study-prostate scoring model was calculated on a scale of 0-6 (0: low, 1-2: intermediate, ≥3: high risk). The risk groups stratified castration-resistant prostate cancer (P < 0.0001), cancer-specific survival (P < 0.0001) and overall survival (P < 0.0001) by Kaplan-Meier curve. The Korean Cancer Study-prostate model predicted castration-resistant prostate cancer with a c-index of 0.7242, cancer-specific survival with a c-index of 0.7036 and overall survival with a c-index of 0.5890. The 5-year estimated castration-resistant prostate cancer/cancer-specific death rates were 10.3%/6.3% in the low-risk group, 48.4%/22.2% in the intermediate-risk group and 81.7%/53.1% in the high-risk group. CONCLUSIONS: The Korean Cancer Study-prostate risk classification, a modified Japan Cancer of the Prostate Risk Assessment model, is a simple scoring model for predicting oncological outcomes after primary androgen deprivation therapy.

Effects of an antiadhesive agent on functional recovery of the greater auricular nerve after parotidectomy: a double-blind randomized controlled trial.

PURPOSE: Periauricular sensory deficit occurs frequently after parotidectomy even in cases with preservation of the greater auricular nerve (GAN). This study was performed to evaluate the effects of antiadhesive agent in functional recovery of the GAN after parotidectomy. METHODS: Ninety-eight patients undergoing partial parotidectomy for benign parotid tumors were prospectively enrolled in this multicenter, double-blind randomized controlled study and randomly assigned to either the study or control group. Antiadhesive agent was applied in the study group. The results of sensory tests (tactile, heat, and cold sensitivity) and a questionnaire on quality of life (QoL) were acquired at postoperative 1, 8, and 24 weeks after surgery. Clinical parameters, and the results of the sensory tests and the questionnaire, were compared between the two groups. RESULTS: A total of 80 patients were finally enrolled. On sensory evaluation, tactile sensation and warm sensation in the ear lobule, and warm sensation in the mastoid area, showed significant improvement at 24 weeks postoperatively in the study group. There were no significant differences between the two groups on any questions in the QoL questionnaire, at any follow-up time point. CONCLUSIONS: Antiadhesive agents have some positive effects on functional recovery of the GAN after parotidectomy. Therefore, applying antiadhesive agents after parotidectomy can reduce discomfort in patients.

Combination treatment with docetaxel and histone deacetylase inhibitors downregulates androgen receptor signaling in castration-resistant prostate cancer.

Backgrounds Since most patients with castration-resistant prostate cancer (CRPC) develop resistance to its standard therapy docetaxel, many studies have attempted to identify novel combination treatment to meet the large clinical unmet need. In this study, we examined whether histone deacetylase inhibitors (HDACIs) enhanced the effect of docetaxel on AR signaling in CRPC cells harboring AR and its splice variants. Methods HDACIs (vorinostat and CG200745) were tested for their ability to enhance the effects of docetaxel on cell viability and inhibition of AR signaling in CRPC 22Rv1 and VCaP cells by using CellTiter-Glo™ Luminescent cell viability assay, synergy index analysis and Western blotting. The nuclear localization of AR was examined via immunocytochemical staining in 22Rv1 cells and primary tumor cells from a patient with CRPC. Results Combination treatment with HDACIs (vorinostat or CG200745) and docetaxel synergistically inhibited the growth of 22Rv1 and VCaP cells. Consistently, the combination treatment decreased the levels of full-length AR (AR-FL), AR splice variants (AR-Vs), prostate-specific antigen (PSA), and anti-apoptotic Bcl-2 proteins more efficiently compared with docetaxel or vorinostat alone. Moreover, the combination treatment accelerated the acetylation and bundling of tubulin, which significantly inhibited the nuclear accumulation of AR in 22Rv1 cells. The cytoplasmic colocalization of AR-FL and AR-V7 with microtubule bundles increased after combination treatment in primary tumor cells from a patient with CRPC. Conclusions The results suggested that docetaxel, in combination with HDACIs, suppressed the expression and nuclear translocation of AR-FL and AR-Vs and showed synergistic anti-proliferative effect in CRPC cells. This combination therapy may be useful for the treatment of patients with CRPC.

Androgen deprivation therapy during and after post-prostatectomy radiotherapy in patients with prostate cancer: a case control study.

BACKGROUND: Here we assessed the influence of androgen deprivation therapy (ADT) during and/or after post-prostatectomy radiotherapy (RT) on biochemical recurrence (BCR) and radiographic progression in patients with prostate cancer. METHODS: Patients with prostate cancer who underwent post-prostatectomy RT were analyzed. BCR and radiographic progression after RT were compared according to the concurrent or salvage ADT. Cox regression analyses were used to identify risk factors for BCR and radiographic progression. RESULTS: Of the 227 patients who underwent post-prostatectomy RT, 95 (41.9%) received concurrent ADT for a median of 17.0 months. Despite more aggressive disease characteristics in the concurrent ADT group than in the RT-only group, the former had a better 5-year BCR-free survival rate than the latter (66.1 vs. 53.9%; p = 0.016), whereas the radiographic progression rate was not significantly different between two groups. On the other hand, salvage ADT after post-RT BCR significantly delayed radiographic progression (5-year radiographic progression-free survival; 75.2 vs. 44.5%; p = 0.002). CONCLUSIONS: Concurrent ADT improved BCR-free survival, and salvage ADT after post-RT BCR improved radiographic progression-free survival. To maximize the oncological benefit, ADT of sufficient duration should be implemented.