Dramatic response to pembrolizumab after pseudoprogression in a patient with advanced metastatic castration-resistant prostate cancer.

Introduction: Prostate cancer with a microsatellite instability-high or mismatch repair-deficient status is not common. Few reports of the response to pembrolizumab in metastatic castration-resistant prostate cancer in a real-world setting have been reported. This case report describes a dramatic response to pembrolizumab after initial pseudoprogression in a patient with microsatellite instability-high metastatic castration-resistant prostate cancer. Case presentation: A 70-year-old man was administered pembrolizumab for metastatic castration-resistant prostate cancer after the genetic evaluation of lymphadenectomy revealed a microsatellite instability-high status. His general condition dramatically improved after pseudoprogression. His favorable condition has been maintained for 1 year since the final dose. Conclusion: We experienced a case of dramatic response to pembrolizumab after pseudoprogression in a patient with advanced metastatic castration-resistant prostate cancer. In patients with metastatic castration-resistant prostate cancer and the microsatellite instability-high/mismatch repair-deficient phenotype, a few months follow-up is necessary to evaluate the efficacy of pembrolizumab.

Pre-operative Serum Albumin as a Potential Predictor of Benign Lesions in Renal Masses.

BACKGROUND/AIM: We investigated pre-operative factors for predicting whether renal masses are benign in order to facilitate the selection of optimal candidates for pre-operative biopsy. PATIENTS AND METHODS: We evaluated 278 patients with renal masses suspected to be clinically T1 or T2 renal cell carcinoma. All patients had undergone a partial or radical nephrectomy. Pre-operative parameters, including patient characteristics, tumor size, and blood tests, were utilized to predict which lesions were benign. RESULTS: Twenty-five lesions (9.0%) were benign. Multivariate analysis showed that female sex [odds ratio (OR)=2.92, p=0.016], serum albumin ≥4.3 g/dl (OR=3.50, p=0.013), and tumor size <23 mm (OR=3.96, p=0.002) were significant independent factors for benign renal masses. The incidence of benign lesions in cases with all three factors (female sex, higher serum albumin, and smaller tumor size) was 4 of 16 (25.0%), which was significantly higher (p=0.037) than that in all cases (25/278; 9.0%). CONCLUSION: Relatively high pre-operative serum albumin levels may be a predictor of benign lesions when associated with female sex and smaller tumor size.

MAGE-A4, NY-ESO-1 and SAGE mRNA expression rates and co-expression relationships in solid tumours.

BACKGROUND: Cancer testis (CT) antigens are promising targets for cancer immunotherapies such as cancer vaccines and genetically modified adoptive T cell therapy. In this study, we evaluated the expression of three CT antigens, melanoma-associated antigen A4 (MAGE-A4), New York oesophageal squamous cell carcinoma 1 (NY-ESO-1) and sarcoma antigen gene (SAGE). METHODS: MAGE-A4, NY-ESO-1 and/or SAGE antigen expression in tumour samples was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Informed consent was obtained from individuals prior to study enrolment. RESULTS: In total, 585 samples in 21 tumour types were evaluated between June 2009 and March 2018. The positive expression rates of these CT antigens were as follows: MAGE-A4, 34.6% (range, 30.7-38.7); NY-ESO-1, 21.0% (range, 17.2-25.1); and SAGE, 21.8% (range, 18.5-25.4). The MAGE-A4 antigen was expressed in 54.9% of oesophageal cancers, 37.5% of head and neck cancers, 35.0% of gastric cancers and 34.2% of ovarian cancers; the NY-ESO-1 antigen was expressed in 28.6% of lung cancers, 25.3% of oesophageal cancers and 22.6% of ovarian cancers; and the SAGE antigen was expressed in 35.3% of prostate cancers, 32.9% of oesophageal cancers and 26.3% of ovarian cancers. The most common tumour type in this study was oesophageal cancer. MAGE-A4, NY-ESO-1 and SAGE antigen expression were assessed in 214 oesophageal cancer samples, among which 24 (11.2%) were triple-positive, 58 (27.1%) were positive for any two, 59 (27.6%) were positive for any one, and 73 (34.1%) were triple negative. CONCLUSIONS: Oesophageal cancer exhibited a relatively high rate of CT antigen mRNA expression positivity.

First-in-human phase I clinical trial of the NY-ESO-1 protein cancer vaccine with NOD2 and TLR9 stimulants in patients with NY-ESO-1-expressing refractory solid tumors.

Cholesteryl pullulan (CHP) is a novel antigen delivery system. CHP and New York esophageal squamous cell carcinoma 1 (NY-ESO-1) antigen complexes (CHP-NY-ESO-1) present multiple epitope peptides to the MHC class I and II pathways. Adjuvants are essential for cancer vaccines. MIS416 is a non-toxic microparticle that activates immunity via the nucleotide-binding oligomerization domain 2 (NOD2) and TLR9 pathways. However, no reports have explored MIS416 as a cancer vaccine adjuvant. We conducted a first-in-human clinical trial of CHP-NY-ESO-1 with MIS416 in patients with NY-ESO-1-expressing refractory solid tumors. CHP-NY-ESO-1/MIS416 (µg/µg) was administered at 100/200, 200/200, 200/400 or 200/600 (cohorts 1, 2, 3 and 4, respectively) every 2 weeks for a total of 6 doses (treatment phase) followed by one vaccination every 4 weeks until disease progression or unacceptable toxicity (maintenance phase). The primary endpoints were safety and tolerability, and the secondary endpoint was the immune response. In total, 26 patients were enrolled. Seven patients (38%) continued vaccination in the maintenance phase. Grade 3 drug-related adverse events (AEs) were observed in six patients (23%): anorexia and hypertension were observed in one and five patients, respectively. No grade 4-5 drug-related AEs were observed. Eight patients (31%) had stable disease (SD). Neither augmentation of the NY-ESO-1-specific IFN-γ-secreting CD8+ T cell response nor an increase in the level of anti-NY-ESO-1 IgG1 was observed as the dose of MIS416 was increased. In a preclinical study, adding anti-PD-1 monoclonal antibody to CHP-NY-ESO-1 and MIS416 induced significant tumor suppression. This combination therapy is a promising next step.

Evaluation to Differentiate between Tumor Lesions and the Parenchyma in Partial Nephrectomies for Renal Tumors Based on Quantitative Fluorescence Imaging Using Indocyanine Green Dye.

INTRODUCTION: Near-infrared fluorescence imaging with indocyanine green is a useful tool during partial nephrectomy. Because an accurate method for judging hasn't been established yet, the success rate may be slightly different and inconsistent. MATERIALS AND METHODS: A total of 21 cases with suspected renal cancers who had undergone a partial nephrectomy were enrolled. We examined differences in the success rate between malignant lesions and the parenchyma by quantifying fluorescence in the pre-resection and ex vivo phases. RESULTS: Pre-resection imaging showed a significant degradation of fluorescence in the focused lesion in 76.2% (16/21) of cases. A significant degradation was observed in 73.7% (14/19) of the total malignant lesions, 70.5% (12/17) of cases with a clear cell lesion, 100% (2/2) of cases with non-clear cell lesions, and 100% (2/2) of benign angiomyolipomas. In contrast, imaging of the ex vivo resected specimens showed a significant degradation in fluorescence of the focused lesions in 85.7% (18/21) of cases. A significantly degradation was observed in 84.2% (16/19) of the total malignant lesions, 82.3% (14/17) of cases with a clear cell lesion, 100% (2/2) of cases with non-clear cell lesions, and 100% (2/2) of benign angiomyolipomas. CONCLUSION: We firstly evaluated the efficacy of quantitative indocyanine green-based fluorescence as an objective method.

The GP Score, a Simplified Formula (Bioptic Gleason Score Times Prostate Specific Antigen) as a Predictor for Biochemical Failure after Prostatectomy in Prostate Cancer.

OBJECTIVES: We used a new GP score (Gleason score multiplied by prostate-specific antigen) without the T stage as a predictive value for biochemical failure (BCF) after prostatectomy. MATERIALS AND METHODS: We assessed 459 prostate cancer patients who underwent prostatectomies at our institution. Three sub-groups were defined in terms of D'Amico classification risk (low, intermediate, and high) and Gleason score (low, < 50; intermediate, 50-100; and high GP score, > 100). Risk factors for BCF were evaluated by multivariate analysis with a Cox hazard model. A log-rank test was used to compare the BCF rate in the 2 groups. RESULTS: There was nosignificant difference in the non-BCF rate between the lowrisk and low GP score subgroups or the intermediate risk andintermediate GP score subgroups. In contrast, the non-BCFrate of the high GP score subgroup (42.1%) was significantlylower than that of the high-risk subgroup (66.1%, log-rankp = 0.008). Based on multivariate analysis, a high GP score(p = 0.001; HR 3.78; 95%CI 1.95-7.35) was a significant independent risk factor for BCF after prostatectomy. CONCLUSION: The GP score, consisting of two absolute numbers, may be a valuable predictive factor for BCF after prostatectomy, especially in the high-risk failure group.

Optimal Monitoring of Prostate-Specific Antigen Detects Prostate Cancer at the Localized Stage after Photoselective Vaporization for Benign Prostatic Hyperplasia.

INTRODUCTION: Photoselective vaporization of the prostate (PVP) does not provide prostate tissue for pathologic analysis. Here, we carried out early monitoring for prostate cancer by measuring prostate-specific antigen (PSA) levels and assessing clinicopathological features after PVP. MATERIALS AND METHODS: Patients (n = 800) who underwent PVP and were followed-up for more than 12 months were analyzed retrospectively. After PVP, PSA levels were measured at 3 and 12 months and each year thereafter. Prostate biopsies were performed when PSA levels increased continuously. We assessed the characteristics of patients diagnosed with prostate cancer. RESULTS: The mean follow-up period was 49 months. After PVP, 54 patients underwent biopsies, and 23 patients were diagnosed with prostate cancer. Overall, 10, 10, and 3 patients had clinical stage T1c, T2a, and T2b disease, respectively, and there were no cases of stage T2c disease or greater. CONCLUSIONS: We found that it was possible to diagnose prostate cancer at a localized stage under our optimal PSA monitoring schedule before and after PVP.

Favorable 10-year outcomes of image-guided intensity-modulated radiotherapy combined with long-term androgen deprivation for Japanese patients with nonmetastatic prostate cancer.

AIM: To investigate 10-year outcomes of high-dose image-guided intensity-modulated radiation therapy (IG-IMRT) combined with long-term androgen deprivation therapy (ADT) for Japanese patients with nonmetastatic prostate cancer. METHODS: A retrospective analysis was performed on 208 Japanese patients with T1-4N0M0 prostate cancer, who underwent definitive IG-IMRT from 2006 to 2010 at our single institution. The median dose was 78 Gy (74-78) and median ADT time was 32 months (6-151). The risk stratification followed the National Comprehensive Cancer Network criteria. A biochemical relapse was defined as nadir plus 2.0 ng/mL. Toxicity was scored with the Radiation Therapy Oncology Group morbidity scale. RESULTS: The median follow-up time was 102 months. For low-, intermediate-, high-, and very-high-risk groups, the 10-year biochemical disease-free survival rates were 100%, 84%, 90%, and 72%, respectively (P = 0.008); clinical relapse-free survival rates were 100%, 100%, 100%, and 81%, respectively (P < 0.001); and cancer-specific survival rates were 100%, 100%, 100%, and 89%, respectively (P = 0.13). The independent prognostic factors influencing biochemical relapse were younger age, Gleason score ≥ 8, and radiation dose < 78 Gy in the multivariate analysis (P = 0.006, 0.014, and 0.013). The 10-year cumulative incidence of late grade 2 or higher gastrointestinal and genitourinary toxicities were 12% and 13%, respectively. No events of grade 4 or 5 were observed. CONCLUSIONS: This study suggest that high-dose IG-IMRT combined with long-term ADT is effective and implementable, leading to excellent 10-year outcomes for Japanese patients with nonmetastatic prostate cancer.

Long-Term Management of Incidental Bladder Cancer Detected in Patients Undergoing Prostatectomy for Prostate Cancer.

INTRODUCTION: At our institution, screening for incidental bladder cancer is routinely performed to avoid tumor cell dissemination caused by surgery in patients undergoing prostatectomy for prostate cancer (PCa). Here, we report the long-term clinical results in patients with incidental bladder cancer detected by routine screening prior to prostatectomy. MATERIALS AND METHODS: Between January 2003 and December 2013, 430 patients undergoing prostatectomy for resection of PCa were enrolled in this cohort study. All patients underwent screening with cystoscopy, urinary sediment analysis, and urinary cytology to detect incidental bladder cancer. The clinical outcomes of cases with incidental bladder cancer were evaluated. RESULTS: The incidence of incidental bladder cancer was 2.1% (9/430). All tumors were single papillary tumors located around the urinary orifice or lateral side and were diagnosed as urothelial cancer (UC). No significant findings were detected by urinary sediment analysis or urinary cytology. Pathological results of transurethral resections revealed 5 cases of pTa with Grade 1 UC and 4 cases of pTa with Grade 2 UC. Androgen-deprivation therapy was administered to 8/9 patients. During the observation period (average of 7.2 years), UC recurrence was detected in 2 cases (2 and 7.3 years). However, transurethral resection successfully removed the tumor completely. After an average of 19.6 months (12-25 months) without UC recurrence, 7 patients (77.8%) underwent prostatectomy, and 2 patients received radiation or androgen-deprivation therapy. Prostatectomy was carried out without dissemination of UC during the observation period. CONCLUSION: Incidental UC was detected in 2.1% of prostatectomy candidates. Preoperative routine screening with flexible cystoscopy was useful to detect early incidental UC.

Effects of dose-escalated radiotherapy in combination with long-term androgen deprivation on prostate cancer.

OBJECTIVE: We aimed to examine the effects of a dose escalation for prostate cancer patients receiving long-term androgen deprivation therapy (ADT). METHODS: A retrospective analysis of 605 patients treated with radiotherapy (RT) and long-term ADT (National Comprehensive Cancer Network criteria-defined intermediate-risk, minimum 10 months; high-risk and very-high-risk, minimum 20 months) was performed. The median ADT time was 31 months. Cox's proportional hazards models were used to compare biochemical disease-free survival (bDFS), clinical relapse-free survival (cRFS) and overall survival (OS) between the ≥70, <78 Gy group and 78 Gy group in a univariate analysis and to assess the effects of the dose escalation on bDFS in a multivariate analysis. RESULTS: After a median follow-up of 70 months, 5-year bDFS was significantly better in the 78 Gy group than in the ≥70, <78 Gy group [96 vs 83%; hazard ratio 3.6 (95% confidence interval 2.2-6.1); p < 0.001]. 5-year cRFS and OS were similar between the two groups. The multivariate analysis showed that RT dose was still an independent prognostic factor of bDFS (p = 0.005). CONCLUSION: The results of the present study suggest that dose escalations result in significant improvements in bDFS, even when used in combination with long-term ADT. A longer follow-up is needed to clarify the effects of dose escalations on cRFS and OS. Advances in knowledge: It remains unclear whether high-dose RT is necessary for improving the outcomes of patients receiving long-term ADT. The results suggest that dose escalations result in significant improvements in biochemical control.

Very high-risk prostate cancer: stratification by outcomes of radiotherapy and long-term androgen deprivation therapy.

AIM: The definition of very high-risk (VHR) prostate cancer is currently based on the study of radical prostatectomy. We aimed to identify a suitable definition for VHR group following external beam radiation therapy (EBRT) and long-term androgen-deprivation therapy (ADT). METHODS: This retrospective study included 356 high-risk patients treated with EBRT and long-term ADT. A median follow-up time was 68 months. At first, associations of previously described prognostic factors with biochemical disease-free survival (bDFS), clinical relapse-free survival (cRFS) and prostate cancer-specific survival (CSS) were examined. Second, the combination of significant adverse factors in the first analysis served as VHR test definitions. For each factor, a Cox proportional hazards model was used to calculate their hazard ratios for bDFS and cRFS. The logrank test was used to evaluate the association between each factor and CSS. RESULTS: Primary Gleason pattern 5, T4 and ≥ 5 or 4 cores with Gleason score 8-10 were risk factors associated with bDFS, cRFS and CSS. Eleven VHR test definitions composed of these adverse factors were associated significantly with bDFS, cRFS and CSS. The final definition was described by primary Gleason pattern 5 or T4 or ≥ 4 cores with Gleason score 8-10 because of the largest sample size of 38% among 11 test definitions. bDFS, cRFS and CSS of the VHR group were significantly lower compared with other high-risk patients (P < 0.001, P < 0.001 and P = 0.015, respectively). CONCLUSION: These VHR criteria were best fitted following EBRT with long-term ADT.

[A Case of Intrascrotal Liposarcoma].

A 69-year-old man was referred to our hospital with the chief complaint of a painless right scrotal swelling gradually increasing in size during the past 10 years. Testicular tumor markers were within the normal range. Ultrasonography showed an intrascrotal homogeneous mass. Computed tomography and magnetic resonance imaging revealed an inguinal mass, which mainly consisted of fat signal area and partially well enhanced in vascular density. Pre-surgical diagnosis was liposarcoma of spermatic cord estimated by radiographic examination and resection of the right intrascrotal tumor with high inguinal orchitectomy was performed. Histopathological diagnosis revealed well-differentiated liposarcoma. No recurrence phenomenon has been observed after 12 months without any adjuvant therapy. This case is the 129th report of intrascrotal liposarcoma in the Japanese literature.

Histone Deacetylase Inhibition in Prostate Cancer Triggers miR-320-Mediated Suppression of the Androgen Receptor.

Targeting androgen receptor (AR) by pharmacologic intervention is one of the effective approaches for treatment of malignant prostate cancers. Histone deacetylase (HDAC) alters the epigenetic status of tumor-associated genes, including those for miRNAs (miRNA), and affects the behavior of cancers. Here, we examined the molecular effects of a HDAC inhibitor, OBP-801, on AR expression and tumor cell growth in prostate cancers. Treatment with OBP-801 efficiently suppressed cell growth of three prostate cancer lines (22Rv1, VCaP, and LNCaP), together with AR downregulation, regardless of their hormone sensitivity. Intriguingly, this effect by OBP-801 was not due to decreased transcriptional activity of the AR gene, but due to posttranscriptional regulation, namely by miRNA-mediated suppression. Among the upregulated miRNAs after OBP-801 treatment in the three prostate cancer cell lines, miR-320a, whose expression was significantly correlated with prognosis of prostate cancers (P = 0.0185), was the most closely associated with AR expression. An miR-320a mimic suppressed AR protein expression together with growth suppression, while anti-miR-320a oligonucleotide significantly abrogated the growth suppression by OBP-801 treatment. FISH analysis revealed that miR-320a was highly expressed in human normal prostate luminal cells, but was rarely expressed in prostate cancer cells. In an AR-dependent prostate tumorigenic rat model, OBP-801 treatment profoundly increased miR-320a expression and repressed prostate tumorigenesis. Our data demonstrated that OBP-801 effectively suppressed AR activity via epigenetic upregulation of miR-320a, which resulted in tumor cell growth suppression of prostate cancers. OBP-801 may be a potent AR-targeting therapeutic reagent in AR-positive prostate cancer regardless of androgen dependency. Cancer Res; 76(14); 4192-204. ©2016 AACR.

High-dose radiotherapy with helical tomotherapy and long-term androgen deprivation therapy for prostate cancer: 5-year outcomes.

PURPOSE: We aimed to examine outcomes of high-dose radiotherapy with helical tomotherapy (HT) and long-term androgen deprivation therapy (ADT) for T1-4N0M0 prostate cancer. METHODS: A total of 391 patients treated with HT between June 2006 and December 2013 were included in this retrospective study. All patients received neoadjuvant ADT for a median duration of 10 months followed by HT at a median dose of 78 Gy [interquartile range (IQR) 78-78]. The times of median adjuvant and total ADT were 19 and 27 months (IQR 20-31), respectively. The risk stratification followed the 2015 National Comprehensive Cancer Network criteria. Biochemical disease-free survival (bDFS) followed the Phoenix definition. Toxicity was scored according to the Radiation Therapy Oncology Group morbidity grading scale. RESULTS: Median follow-up from HT start was 60 months (IQR 42-81). Five-year bDFS rates for low-, intermediate-, high-, and very-high-risk groups were 100, 98.2, 97.7, and 87.9 %, respectively. We observed clinical relapse in nine very-high-risk patients and one high-risk patient, resulting in a 5-year clinical relapse-free survival of 100, 100, 99.4, and 91.7 %, respectively, for each risk group. Three patients died of prostate cancer, resulting in a 5-year prostate cancer-specific survival of 99.6 %. The late grade 2 or higher gastrointestinal and genitourinary toxicities were 9.7 and 10.7 %. No cardiovascular fatal events were observed. CONCLUSIONS: This report confirmed the excellent outcomes with acceptable late toxicities with the combination of HT and long-term ADT. Longer follow-up is crucial to further determine the treatment effect and toxicity.

Clinical Effect of Switching from a Luteinizing Hormone-Releasing Hormone Agonist to an Antagonist in Patients with Castration-Resistant Prostate Cancer and Serum Testosterone Level ≥ 20 ng/dl.

INTRODUCTION: The efficacy of conversion from a luteinizing hormone-releasing hormone agonist to an antagonist was evaluated prospectively in patients with castration-resistant prostate cancer. MATERIALS AND METHODS: From October 2012 to December 2014, 8 cases with a serum testosterone level ≥ 20 ng/dl during following androgen deprivation therapy were enrolled and received degarelix monthly. The primary end-pointgoal was to determine the effective prostate-specific antigen response rate. The secondary end-pointgoal was to assess the proportion of cases with a decrease in serum testosterone level to < 20 ng/ml. RESULTS: One patient achieved a complete response, with a prostate-specific antigen level of 0.02 ng/ml at the nadirend of the study. The effective response rate was 25.0% (2/8), and the proportion of cases with prostate-specific antigen decline was 62.5% (5/8). In 5/8 cases (5/8, 62.5%), serum testosterone levels declined to < 20 ng/dl. CONCLUSION: Switching to a luteinizing hormone-releasing hormone antagonist in patients with testosterone levels ≥ 20 ng/dl may be an option in sequential androgen deprivation therapy for some patients.

Aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 1B (ADH1B) polymorphisms exacerbate bladder cancer risk associated with alcohol drinking: gene-environment interaction.

Although a range of chemical exposures (cigarette smoking and occupational exposure) are recognized risk factors for the development of bladder cancer (BCa), many epidemiological studies have demonstrated that alcohol drinking is not associated with BCa risk. Aldehyde dehydrogenase 2 (ALDH2; rs671, Glu504Lys) and alcohol dehydrogenase 1B (ADH1B; rs1229984, His47Arg) polymorphisms impact the accumulation of acetaldehyde, resulting in an increased risk of various cancers. To date, however, no studies evaluating the association between BCa risk and alcohol drinking have considered these polymorphisms. Here, we conducted a matched case-control study to investigate whether ALDH2 and ADH1B polymorphisms influence BCa risk associated with alcohol drinking. Cases were 74 BCa patients and controls were 740 first-visit outpatients without cancer at Aichi Cancer Center Hospital between January 2001 and December 2005. Odds ratio (OR), 95% confidence interval (CI) and gene-environment interaction were assessed by conditional logistic regression analysis with adjustment for potential confounders. Results showed that ALDH2 Glu/Lys was associated with a significantly increased risk of BCa compared with Glu/Glu (OR 2.03, 95% CI 1.14-3.62, P = 0.017). In contrast, ALDH2 Glu/Lys showed no increase in risk among the stratum of never drinkers compared with Glu/Glu, indicating a gene-environment interaction. ADH1B His/Arg had an OR of 1.98 (1.20-3.24, P = 0.007) compared with His/His. ADH1B Arg+ showed a similar OR and 95% CI. Individuals with ALDH2 Glu/Lys and ADH1B Arg+ had the highest risk of BCa compared with ALDH2 Glu/Glu and ADH1B His/His [OR 4.00 (1.81-8.87), P = 0.001].

International prostate symptom score (IPSS) change and changing factor in intensity-modulated radiotherapy combined with androgen deprivation therapy for prostate cancer.

The purposes of this study on prostate cancer are to demonstrate the time course of International Prostate Symptom Score (IPSS) after intensity-modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT) and to examine the factor associated with the IPSS change. This study included 216 patients treated with IMRT between 2006 and 2010. Patients were evaluated in three groups according to baseline IPSS as defined by the American Urological Association classification, where IPSSs of 0 to 7, 8 to 19, and 20 to 35 represent mild (n = 124), moderate (n = 70), and severe (n = 22) symptom groups, respectively. The average IPSSs ± standard deviation at baseline vs. those at 24 months after IMRT were 3.5 ± 2.1 vs. 5.1 ± 3.6 in the mild group (P < 0.001), 12.6 ± 3.4 vs. 10.0 ± 6.0 in the moderate group (P = 0.0015), and 23.8 ± 2.9 vs. 14.4 ± 9.1 in the severe group (P < 0.001). Among factors of patient and treatment characteristics, age, IPSS classification, pretreatment GU medications, and positive biopsy rates were associated with the IPSS difference between baseline and 24 months (P = 0.023, < 0.001, 0.044, and 0.028, respectively). In conclusion, patients with moderate to severe urinary symptoms can exhibit improvement in urinary function after IMRT, whereas patients with mild symptoms may have slightly worsened functions. Age, baseline IPSS, GU medications, and tumor burden in the prostate can have an effect on the IPSS changes.

Review of Bioptic Gleason Scores by Central Pathologist Modifies the Risk Classification in Prostate Cancer.

OBJECTIVES: The Gleason score (GS) is the primary classification of clinical risk in prostate cancer (PCa). Here, we estimated the factors predictive of accordance of local and central pathologist-dependent GS and clinical risk classification in an increased number of cases. METHODS: Between January 2009 and December 2013, 388 patients were diagnosed with PCa by 80 independent pathologists from local communities and were referred to our hospital. Validation of the GS with needle-core biopsy specimens was carried out by a single central pathologist, and clinical risk, according to the D'Amico risk classification, was determined. Discrepancies between the GS and risk classification, based on the GS estimated by the local or central pathologist, were reviewed, and predictive factors for accordance of clinical risk classification were estimated. RESULTS: When pathological results were compared, 59.5% of cases were given concordant GSs by local and central pathologists. A significant discrepancy existed in the classification of intermediate risk (p < 0.0001). Multivariate analysis indicated that local pathologist-dependent GS7, lower prostate-specific antigen (≤ 10 ng/ml), and lower T stage (T1 or T2a) were significant predictive factors for discordance with the central pathologist-dependent risk classification. CONCLUSION: Review of bioptic GSs by central pathologists affected discrepancies in risk classification in patients with PCa.

Additional Midline Biopsies of the Peripheral Zone Associated with the First Endorectal Standard Sextant Pattern Improves the Accuracy of Prostate Cancer Detection in Japanese Patients.

OBJECTIVES: This study was designed to estimate the improved accuracy of prostate cancer (PCa) detection resulting from additional midline biopsies of the peripheral zone in first standard biopsy. PATIENTS AND METHODS: Patients were classified into 3 groups: 402 cases of sextant biopsies (1995-2002), 488 cases of 8-core biopsies with 2 additional midline biopsies (2003-2006), and 391 cases of 10-core biopsies with 4 additional midline biopsies (2007-2012). The positive rate of each number of biopsies and changes in positive rates associated with prostate specific antigen (PSA) ranges were estimated. RESULTS: The positive rate of core biopsy significantly improved with increasing numbers of core biopsies (30.1% for sextant, 43.4% for 8-core biopsies, and 53.1% for 10-core biopsies). The accuracy of biopsies for each PSA range also significantly improved (22.3% for sextant, 30.0% for 8-core biopsies, and 43.2% for 10-core biopsies in the PSA gray zone [4.01-10 ng/ml]; and 26.5% for sextant, 52.9% for 8-core biopsies, and 71.8% for 10-core biopsies in the intermediate PSA range [10.1-20 ng/ml]). In the 208 cases with positive results using the 10-core biopsy method, the distribution of Gleason scores did not differ between the sextant only group and the midline site only group. CONCLUSIONS: Additional midline biopsy was associated with improved accuracy of positive core biopsies in Japanese patients with a PSA range of 4.01-20 ng/ml. © 2015 S. Karger AG, Basel.

A genome-wide association study of serum levels of prostate-specific antigen in the Japanese population.

BACKGROUND: Prostate-specific antigen (PSA) is a useful marker for prostate cancer (PCa) and is widely used for screening of PCa. Previous studies have shown that genetic components influence the levels of PSA, and some of these genetic components would lead to better diagnostic sensitivity and specificity to PCa. However, genetic studies for PSA from Asian countries are limited. Our aim was to identify genetic components influencing PSA levels in the Japanese population using genome-wide association study (GWAS) and to analyse whether genetic components would lead to better screening abilities of PCa. METHODS: We performed a GWAS comprising 1086 male subjects using 303 283 single nucleotide proteins, followed by a replication study of 1302 subjects. PSA levels were quantified by chemiluminescence immunoassay method. Quantitative linear regression analysis was performed to assess genetic components of PSA levels. A total of 413 subjects with prostate biopsies were analysed to examine whether genetic determinants would improve diagnostic ability. RESULTS: Rs16856139 in SLC45A3, the same region as the previous Chinese study, showed an overall significant association with PSA levels (p=2.4×10(-11)) along with rs1058205 in KLK3. In silico analysis revealed significant association between rs16856139 and expression of SLC45A3. Genetic scores of PSA showed a dose-dependent decrease of area under curve (AUC) of PCa and successfully subgrouped the individuals with significantly different AUC (p≤0.0097). CONCLUSIONS: Rs16856139, associated with the expression of SLC45A3, is significantly associated with the levels of PSA in the Japanese population. Classification of subjects based on PSA genetic determinants would improve screening ability of PSA to detect PCa.