Pretreatment Prostate-specific Antigen Research Articles

Improved rectal dosimetry with the use of SpaceOAR during high-dose-rate brachytherapy

PurposeHydrogel spacers have been suggested to limit rectal radiation dose with improvements in clinical outcomes in patients undergoing external beam radiation treatment for prostate cancer. No studies to date have assessed the utility and dosimetric effect of SpaceOAR (Augmenix, Inc, Waltham, MA), the only Food and Drug Administration–approved hydrogel rectal spacer, for high-dose-rate (HDR) brachytherapy. MethodsEighteen consecutive patients scheduled for HDR brachytherapy in the treatment of prostate cancer underwent transperineal ultrasound-guided placement of 10 cc of SpaceOAR hydrogel following catheter implantation. Treatment plans were generated using an inverse planning simulated annealing algorithm. Rectal dosimetry for these 18 patients was compared with the 36 preceding patients treated with HDR brachytherapy without SpaceOAR. ResultsFifty-four plans were analyzed. There was no difference in age, pretreatment prostate-specific antigen, Gleason score, clinical stage, prostate volume, or contoured rectal volume between those who received SpaceOAR and those who did not. Patients who received SpaceOAR hydrogel had significantly lower dose to the rectum as measured by percent of contoured organ at risk (median, V80 < 0.005% vs. 0.010%, p = 0.003; V75 < 0.005% vs. 0.14%, p < 0.0005; V70 0.09% vs. 0.88%, p < 0.0005; V60 = 1.16% vs. 3.08%, p < 0.0005); similar results were seen for rectal volume in cubic centimeters. One patient who received SpaceOAR developed a perineal abscess 1 month after treatment. ConclusionsTransperineal insertion of SpaceOAR hydrogel at the time of HDR brachytherapy is feasible and decreases rectal radiation dose. Further investigation is needed to assess the clinical impact of this dosimetric improvement and potential toxicity reduction.

Associations Between Prostate Volume and Oncologic Outcomes in Men Undergoing Focal Cryoablation of the Prostate.

The purpose of this study was to assess the relationship of total prostate volume (TPV) and oncologic outcomes following focal prostate cryoablation. A query of the Cryo On-Line Database (COLD) registry for men who underwent primary focal prostate cryoablation revealed 829 patients with complete data. The impact of TPV on oncologic outcomes including progression-free survival (PFS) and post-cryoablation biopsy outcome was assessed using Kaplan-Meier curves and Cox and logistic regression models. The median follow-up time was 25.2 months (interquartile range [IQR], 12.7-48.2 months). The median age at time of treatment was 68 years (IQR, 63-74 years) with median prostate-specific antigen (PSA) 5.6 ng/mL (IQR, 4.4-7.5 ng/mL), and median TPV 35 mL (IQR, 26.5-46 mL). PFS was achieved in 83.2%, with positive post-cryoablation biopsy detected in 81 (35.7%) of 228 patients. Higher TPV was associated with higher biochemical progression (BP) using the Phoenix definition (39 vs. 34.5 mL; P= .003) and was an independent predictor of BP (hazard ratio, 1.01; P= .02). Conversely, men who had a positive post-cryoablation biopsy had significantly smaller median TPV on univariate and multivariate analyses (31 vs. 39 mL; P< .001), (odds ratio, 0.97; P= .001), respectively. Higher median pretreatment PSA density was associated with higher BP (0.18 vs. 0.16; P= .005) and positive post-cryoablation biopsy rates (0.2 vs. 0.16; P=.003). Prostate volume has contradictory effects on BP and post-cryoablation biopsy outcome in men who underwent primary focal prostate cryoablation. Remnant viable tissue in larger prostates continues to produce more PSA over time, which may impact BP. This may raise the need to develop a new definition for oncologic success following focal gland therapy rather than the American Society for Radiation Oncology (ASTRO) and Phoenix definitions.

Predictive value of epithelial-mesenchymal-transition (EMT) signature and PARP-1 in prostate cancer radioresistance.

Epithelial-mesenchymal-transition (EMT) has been previously identified as a contributor to prostate cancer progression to metastasis and therapeutic resistance to antiandrogens and radiotherapy. In this study we conducted a retrospective analysis to investigate the significance of radiation-induced EMT and consequential changes to the tumor microenvironment in biochemical recurrence and response to radiotherapy in prostate cancer patients. Expression profiling and localization for EMT effectors, E-Cadherin, N-Cadherin, β-catenin and Vimentin was assessed in human prostate tumor specimens pre- and post-radiotherapy and correlated with biochemical recurrence. In addition, immunoreactivity of the DNA repair enzyme, polymerase (PARP-1) and the cytoskeletal-remodeling regulator, cofilin was evaluated in prostate tumor specimens pre- and post-radiotherapy and correlated with pre-treatment prostate-specific antigen levels (PSA). Our findings identified that characteristic changes associated with the EMT phenotype and its reversal to mesenchymal-epithelial-transition (MET) within the tumor microenvironment correlate with biochemical recurrence and resistance to radiotherapy among prostate cancer patients. Moreover, elevated PARP-1 expression among the tumor cells undergoing EMT implicates that DNA repair mechanisms may potentially reverse the cytotoxic effects of radiotherapy-induced DNA breaks. Our results suggest that EMT programming effectors, integrated with the actin cytoskeleton regulator cofilin and mesenchymal PARP-1 expression profile provide a signature of potential predictive significance of therapeutic response to radiotherapy in a subset of prostate cancer patients.

An evaluation of irreversible electroporation thresholds in human prostate cancer and potential correlations to physiological measurements.

Irreversible electroporation (IRE) is an emerging cancer treatment that utilizes non-thermal electric pulses for tumor ablation. The pulses are delivered through minimally invasive needle electrodes inserted into the target tissue and lead to cell death through the creation of nanoscale membrane defects. IRE has been shown to be safe and effective when performed on tumors in the brain, liver, kidneys, pancreas, and prostate that are located near critical blood vessels and nerves. Accurate treatment planning and prediction of the ablation volume require a priori knowledge of the tissue-specific electric field threshold for cell death. This study addresses the challenge of defining an electric field threshold for human prostate cancer tissue. Three-dimensional reconstructions of the ablation volumes were created from one week post-treatment magnetic resonance imaging (MRIs) of ten patients who completed a clinical trial. The ablation volumes were incorporated into a finite element modeling software that was used to simulate patient-specific treatments, and the electric field threshold was calculated by matching the ablation volume to the field contour encompassing the equivalent volume. Solutions were obtained for static tissue electrical properties and dynamic properties that accounted for electroporation. According to the dynamic model, the electric field threshold was 506 ± 66 V/cm. Additionally, a potentially strong correlation (r = −0.624) was discovered between the electric field threshold and pre-treatment prostate-specific antigen levels, which needs to be validated in higher enrollment studies. Taken together, these findings can be used to guide the development of future IRE protocols.

Comparison of Toxicities in High Dose Rate Versus Low Dose Rate Brachytherapy as Monotherapy in Patients with Low to Favorable Intermediate Risk Prostate Cancer

The purpose of our study was to compare acute and late toxicities of high dose rate (HDR) brachytherapy and low dose rate (LDR) permanent iodine or palladium seeds as monotherapy in patients with low and favorable intermediate risk prostate cancer. We retrospectively examined patients with biopsy proven, low to favorable intermediate risk prostate cancer treated with interstitial brachytherapy monotherapy from 1998-2016 at a single institution. Patients selected were restricted to T stage ≤ T2c, Gleason score ≤7, and prostate specific antigen (PSA) less than 20 ng/ml. For each case of prostate brachytherapy, needles/seeds were implanted transperineally via trans-rectal ultrasound guidance. Dose for LDR was 145 Gy and HDR was 27 Gy in 2 fractions. The Common Toxicity Criteria scale, version 2.0 and 3.0 were used to score the acute (<12 months after brachytherapy) and late (≥ 12 months after brachytherapy) toxicities. Chi square analysis tested for associations between toxicity and treatment technique. Logistic regression was used in multivariable analyses (MVA). A total of 572 patients were included, including 97 treated with HDR using 192iridium (192Ir), and 475 treated with LDR using 125iodine (125I) or 103palladium (103Pd). The median follow up time was 9.2months (range 3.1-145.3) for HDR patients and 53.1 months (range 0.2-198.6) for LDR patients. The two treatment groups were well-balanced with respect to age, T stage, ethnicity, and implanted prostate gland volume. A majority of patients had T1c disease and pretreatment PSA less than 10 ng/ml. 69% of HDR patients had Gleason score of 7 while 2.5% of LDR patients had Gleason score of 7. On univariate analysis, HDR brachytherapy was associated with lower rate of grade 2+ acute GU toxicity (14% vs 38%, p <0.0001) and grade 2+ late GU toxicity (10% vs 31%, p< 0.0001). Acute GI toxicity was low at 3% for both HDR and LDR; late GI toxicity were 6% and 7% (p= 0.63) for HDR and LDR, respectively. In MVA, only LDR was independently associated with increased risk of grade 2+ acute GU toxicity (OR 2.4, 95% CI 1.1-5.3), but it was no longer associated with increased risk of grade 2+ late GU toxicity (OR 1.0, 95% CI 0.5-2.3). MVA demonstrated no difference between the two treatment methods with regard to acute or late GI toxicity. Acute and late GI toxicity was rare in patients treated with brachytherapy. The use of HDR brachytherapy as monotherapy was associated with a significantly lower risk of grade 2+ acute GU toxicity but similar grade 2+ late GU toxicity compared to LDR. Our results suggest HDR may be the preferred brachytherapy option in patients with clinically localized prostate cancer due to the better acute safety profile.

Clinical Study on the Efficacy and Continuous Docetaxel Based Chemotherapy Treatment for Castration-Resistant Prostate Cancer

We report a retrospective study on the efficacy, adverse events and the factors for continuous docetaxel (DOC) therapy for patients with castration-resistant prostate cancer (CRPC). Between April 2007 and April 2015, 37 CRPC patients were treated with DOC therapy at Kanazawa Medical University Hospital. DOC was administered every 3 weeks at 70 mg/m2. Prostatic specific antigen (PSA) level, adverse events, cycles of DOC therapy, survival time and clinical passage were examined. Fifteen patients showed a decrease in PSA level of 50% or more, 9 patients showed less than 50% decrease in PSA level and 13 patients showed no decrease in PSA level. Adverse effect of grade 3 consisted of neutropenia in 29.7% and leukocytopenia in 10.8%. The median number of treatment cycles was 11.7 courses. The patients were divided into two groups ; the first group comprised of 26 patients who received short-term DOC therapy (≤10 cycles) and the second group comprised of 11 patients who received long-term DOC therapy (≥11 cycles). The 1-year survival rate was 59 and 100% for the short-term and long-term groups, respectively. Long-term treatment was related to pretreatment PSA nadir, time to progression of CRPC and serum lactate dehydrogenase level.

MP86-14 PROSTATE SPECIFIC ANTIGEN AND HEALTH-RELATED QUALITY-OF-LIFE OUTCOMES IN UNINSURED MEN WITH PROSTATE CANCER

You have accessJournal of UrologyGeneral & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making V1 Apr 2017MP86-14 PROSTATE SPECIFIC ANTIGEN AND HEALTH-RELATED QUALITY-OF-LIFE OUTCOMES IN UNINSURED MEN WITH PROSTATE CANCER Avi Baskin, Joseph Shirk, Lorna Kwan, and Karim Chamie Avi BaskinAvi Baskin More articles by this author , Joseph ShirkJoseph Shirk More articles by this author , Lorna KwanLorna Kwan More articles by this author , and Karim ChamieKarim Chamie More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2697AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate Specific Antigen (PSA) continues to be a useful marker of risk strata and disease progression for patients with prostate cancer. While there have been multiple investigations into the relationship between PSA and mortality, there is a dearth in the literature describing the association between PSA and health-related quality-of-life (HRQOL) outcomes. In this study, we hypothesize that PSA is inversely related with HRQOL in patients with prostate cancer. METHODS Our cohort consisted of a prospective analysis of men from a state-funded program that provides free prostate cancer care to underinsured and uninsured low-income California residents with prostate cancer. Highest pre-treatment PSA was our primary exposure variable of interest. We created 4 strata: <10, 10-19.9, 20-49.9 and ≥50 PSA. The primary outcome variables were HRQOL at program enrollment using the RAND SF-12 to measure physical and mental health, and the UCLA Prostate Cancer Index Short Form to measure urinary, sexual and bowel habits in two domains: bother and function. Controlling for demographic and clinical variables, we conducted separate multivariable linear regression analysis for each quality of life domain. RESULTS 627 men were eligible for the study. Age, ethnicity, primary language, education and Charlson comorbidity did not differ across PSA strata. Compared to the referent group PSA <10, those with PSA ≥50 were more likely to receive androgen deprivation therapy as their primary form of treatment (p <0.01). Patients with PSAs 10-19.9 were more likely to have sexual bother (β=11.1, p<0.03) compared to the referent group. (See Table) There were no other differences in other HRQOL domains across PSA strata. CONCLUSIONS In this population, we found no statistically significant difference in HRQOL outcomes by PSA level. The finding that patients with very elevated PSA levels having outcomes that were no worse than patients with less aggressive disease is important clinically because most quality of life detriments tend to be from treatment of localized disease. Further, these findings will inform physicians on patient symptomatology despite PSA level. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1161-e1162 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Avi Baskin More articles by this author Joseph Shirk More articles by this author Lorna Kwan More articles by this author Karim Chamie More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

68Ga-PSMA Ligand PET/CT-based Radiotherapy for Lymph Node Relapse of Prostate Cancer After Primary Therapy Delays Initiation of Systemic Therapy

To evaluate 68Ga-PSMA ligand positron-emission tomography-computed tomography (PET/CT)-based radiotherapy for lymph node metastases of prostate cancer after primary therapy. Twenty-three patients received radiotherapy for PSMA ligand-positive lymph node metastases. The median follow-up time was 12.4 (range=6.0-28.5) months. The median pre-treatment prostate-specific antigen (PSA) decreased from 2.75 (range=0.52-8.92) ng/ml to a nadir of 1.37 (range=0.11-8.00) ng/ml (p=0.001) following radiotherapy. Except for one patient (4.4%), PSA level decreased in 22 patients (95.6%). The biochemical failure-free survival and time to initiation of systemic therapy at the median follow-up were 95.6% and 100%, respectively. Three patients (12.9%) presented with recurrent disease outside the initial radiation field. No grade III acute toxicities or late grade II toxicities were observed. 68Ga-PSMA ligand PET/CT-based radiotherapy is a promising local treatment option for isolated lymph node metastases of prostate cancer.

Pretreatment prostate specific antigen doubling time as prognostic factor in prostate cancer patients.

Despite the prostate-specific antigen (PSA) serum level commonly uses as tumor marker in diagnosis of prostate cancer, it seems that PSA doubling time (PSADT) could be more useful indicator of tumor behavior and of prognosis for patients. The results of hormone and radiation therapy were evaluated for 912 prostate cancer having at least 2 PSA tests before the treatment was started. Clustering procedure (selection of homogenous group) was performed by using PSADT as the classification marker. The rate of PSADT was estimated for different dissemination rate, age, Gleasons's score and education level. PSADT index inversely correlated with the rate of prostate cancer dissemination, Gleason's score and the level of education were directly correlated with the age of patients. Survival time was longer and PSADT index was higher in “slow” tumor growing subgroups in local, local-advanced and metastatic prostate cancer patients than these in “fast” subgroups. The study confirmed the prognostic value of pretreatment PSADT in prostate cancer patients independently of cancer progression. No significant relationship exists between the authors and the companies/organizations whose products or services may be referenced in this article.

Pre-treatment PSA- progression as a negative prognostic factor in patients using 5-alpha-reductase inhibitors prior to radiotherapy for prostate cancer.

96 Background: To investigate the impact of 5-alpha-reductase inhibitors (5-ARIs) usage on radiotherapy outcomes for localized prostate cancer. Methods: From our institutional database of over 2500 patients, we identified 203 patients on a 5-ARI. They were all treated with either external beam radiotherapy (EBRT) or brachytherapy for localized prostate cancer. Patients receiving a 5-ARI were analyzed according to the following prostate cancer progression criteria: a) progression of Gleason score or increase in cancer volume on the biopsy, b) first biopsy positive for cancer after being treated for urinary symptoms with a 5-ARI, and c) prostate-specific antigen (PSA) progression with or without a previous cancer diagnosis. Biochemical failure (BF) was defined by the Phoenix definition. Log-rank test was used for survival analysis. Results: At a median follow-up of 36 months (interquartile range [IQR] 22-52 months), 10 (4.9%) patients experienced BF. 52% of men demonstrated none of the progression criteria, 37% showed only one prostate cancer progression criteria and 11% showed two. Using a univariate analysis, PSA progression (p = 0.004) and appearance of a positive biopsy (p &lt; 0.001) but not Gleason progression (p = 0.3) were a significant predictive factor of BF. With separate multivariate analysis adjusted for the CAPRA score (HR 1.7, 95% CI 1.2-2.3, p = 0.003), a rising PSA (HR 5.7, 95% CI 1.1-28.8, p = 0.04) and the number of cancer progression factors (HR 2.9, 95%CI 1.2-7.0, p = 0.02) remained adverse risk factors. Both Gleason score progression (p = 0.4) and first biopsy positive for cancer (p = 0.13) failed to remain significant. Age and obesity were not significant factors in univariate or multivariate analysis. Conclusions: A PSA progression experienced while under 5-ARI treatment before EBRT or brachytherapy is predictive of worse biochemical outcome. Such details should be considered when counseling men prior to radiation therapy.

A Prospective Trial of Intensity Modulated Radiation Therapy (IMRT) Incorporating a Simultaneous Integrated Boost for Prostate Cancer: Long-term Outcomes Compared With Standard Image Guided IMRT

This report describes the long-term outcomes of a prospective trial of intensity modulated radiation therapy (IMRT), integrating a 111In capromab pendetide (ProstaScint) scan-directed simultaneous integrated boost (SIB) for localized prostate cancer. Seventy-one patients with T1N0M0 to T4N0M0 prostate cancer were enrolled, and their ProstaScint and pelvic computed tomography scans were coregistered for treatment planning.The entire prostate received 75.6Gy in 42 fractions with IMRT, whereas regions of increased uptake on ProstaScint scans received 82Gy as an SIB. Patients with intermediate- and high-risk disease also received 6months and 12months of adjuvant hormonal therapy, respectively. The study enrolled 31 low-, 30 intermediate-, and 10 high-risk patients. The median follow-up was 120months (range, 24-150months). The 10-year biochemical control rates were 85% for the entire cohort and 84%, 84%, and 90% for patients with low-, intermediate-, and high-risk disease, respectively. The 10-year survival rate of the entire cohort was 69%. Pretreatment prostate-specific antigen level >10ng/mL and boost volume of >10% of the prostate volume were significantly associated with poorer biochemical control and survival. The outcomes were compared with those of a cohort of 302 patients treated similarly but without the SIB and followed up for a median of 91months (range, 6-138months). The 5- and 10-year biochemical control rates were 86% and 61%, respectively, in patients without the SIB compared with 94% and 85%, respectively, in patients in this trial who received the SIB (P=.02). The cohort that received an SIB did not have increased toxicity. The described IMRT strategy, integrating multiple imaging modalities to administer 75.6Gy to the entire prostate with a boost dose of 82Gy, was feasible. The addition of the SIB was associated with greater biochemical control but not toxicity. Modern imaging technology can be used to locally intensify the dose to tumors and spare normal tissues, producing very favorable long-term biochemical disease control.

Long-Term Outcomes and Prognosis of Transrectal High-Intensity Focused Ultrasound Therapy for Patients with Localized Prostate Cancer—Therapy after Recurrence and Predictive Factors

Objectives: To evaluate the outcomes and prognosis of high-intensity focused ultrasound (HIFU) therapy for patients with localized prostate cancer, and identify suitable candidates for this therapy by investigating the predictive factors. Methods: The 224 patients (low 54, intermediate 111 and high-risk patients 59) with T1-2 stage were treated using the Sonablate device and followed for over 12 months after treatment. Recurrence was determined based on histological findings, prostate-specific antigen (PSA) failure and local or distant metastasis. The factors which are predicting variables with potential effects were investigated by Kaplan-Meier and multivariate analysis. Results: A total of 255 treatment sessions (193 with one, 31 with two) were performed. No patients died of prostate cancer, but 15 died of other causes and 14 patients were lost during follow-up. The 7-year recurrence-free survival (RFS) rates in all patients were 75%, and 5-year RFS rates were 98%, 84% and 59% in the low, intermediate and high-risk patients respectively. In the 216 patients who underwent histological examination at 6 months or later after HIFU, 25 (12%) were positive. In 77 patients with recurrence after first-HIFU, the second treatments were hormonal therapy and HIFU. Of the 31 patients who underwent a second HIFU, the 5-year RFS rates were 64%, and 5-year RFS rates were 100%, 74% and 33% in the low, intermediate and high-risk patients. The significant predictor for recurrence was risk-group, T-stage (T1 vs T2), Gleason score (≤3 + 4 and ≥4 + 3), pretreatment PSA (<10 vs ≥10 ng/ml) and nadir PSA (<0.1 vs ≥0.1 ng/ml). In 111 patients with intermediate-risk, T-stage and nadir PSA were significantly associated with outcomes. Conclusions: Prognosis of HIFU for Patients with localized prostate cancer was good, and the low and intermediate-risk patients with T1-staging are suitable indications for HIFU. Effective predictors for outcomes were risk-group, T-stage, Gleason score, pretreatment PSA and nadir PSA.

Effect of Prostate Magnetic Resonance Imaging/Ultrasound Fusion-guided Biopsy on Radiation Treatment Recommendations

Targeted magnetic resonance imaging (MRI)/ultrasound fusion prostate biopsy (MRI-Bx) has recently been compared with the standard of care extended sextant ultrasound-guided prostate biopsy (SOC-Bx), with the former associated with an increased rate of detection of clinically significant prostate cancer. The present study sought to determine the influence of MRI-Bx on radiation therapy and androgen deprivation therapy (ADT) recommendations. All patients who had received radiation treatment and had undergone SOC-Bx and MRI-Bx at our institution were included. Using the clinical T stage, pretreatment prostate-specific antigen, and Gleason score, patients were categorized into National Comprehensive Cancer Network risk groups and radiation treatment or ADT recommendations assigned. Intensification of the recommended treatment after multiparametric MRI, SOC-Bx, and MRI-Bx was evaluated. From January 2008 to January 2016, 73 patients received radiation therapy at our institution after undergoing a simultaneous SOC-Bx and MRI-Bx (n=47 with previous SOC-Bx). Repeat SOC-Bx and MRI-Bx resulted in frequent upgrading compared with previous SOC-Bx (Gleason score 7, 6.7% vs 44.6%; P<.001; Gleason score 8-10, 2.1% vs 38%; P<.001). MRI-Bx increased the proportion of patients classified as very high risk from 24.7% to 41.1% (P=.027). Compared with SOC-Bx alone, including the MRI-Bx findings resulted in a greater percentage of pathologically positive cores (mean 37% vs 44%). Incorporation of multiparametric MRI and MRI-Bx results increased the recommended use and duration of ADT (duration increased in 28 of 73 patients and ADT was added for 8 of 73 patients). In patients referred for radiation treatment, MRI-Bx resulted in an increase in the percentage of positive cores, Gleason score, and risk grouping. The benefit of treatment intensification in accordance with the MRI-Bx findings is unknown.

An audit of referral and treatment patterns of high-risk prostate cancer patients in Alberta.

We aimed to determine the impact of clinical practice guidelines (CPG) on rates of radiation oncologist (RO) referral, androgen-deprivation therapy (ADT), radiation therapy (RT), and radical prostatectomy (RP) in patients with high-risk prostate cancer (HR-PCa). All men >18 years, diagnosed with PCa in 2005 and 2012 were identified from the Alberta Cancer Registry. Patient age, aggregated clinical risk group (ACRG) score, Gleason score (GS), pre-treatment prostate-specific antigen (PSA), RO referral, and treatment received were extracted from electronic medical records. Logistic regression modelling was used to examine associations between RO referral rates and relevant factors. HR-PCa was diagnosed in 261 of 1792 patients in 2005 and 435 of 2148 in 2012. Median age and ACRG scores were similar in both years (p>0.05). The rate of patients with PSA >20 were 67% and 57% in 2005 and 2012, respectively (p=0.004). GS ≤6 was found in 13% vs. 5% of patients, GS 7 in 27% vs. 24%, and GS ≥8 in 59% vs. 71% in 2005 and 2012, respectively (p<0.001). In 2005, RO referral rate was 68% compared to 56% in 2012 (p=0.001), use of RT + ADT was 53% compared to 32% (p<0.001), and RP rate was 9% vs. 17% (p=0.002). On regression analysis, older age, 2012 year of diagnosis and higher PSA were associated with decreased RO referral rates (odds ratios [OR] 0.49, 95% confidence interval [CI] 0.39-0.61; OR 0.51, 95% CI 0.34-0.76; and OR 0.64, 95% CI 0.39-0.61), respectively [p<0.001]). Since CPG creation in 2005, RO referral rates and ADT + RT use declined and RP rates increased, which demonstrates a need to improve adherence to CPG in the HR-PCa population.

Favorable Preliminary Outcomes for Men With Low- and Intermediate-risk Prostate Cancer Treated With 19-Gy Single-fraction High-dose-rate Brachytherapy

To report the toxicity and preliminary clinical outcomes of a prospective trial evaluating 19-Gy, single-fraction high-dose-rate (HDR) brachytherapy for men with low- and intermediate-risk prostate cancer. A total of 63 patients were treated according to an institutional review board-approved prospective study of single-fraction HDR brachytherapy. Eligible patients had tumor stage≤T2a, prostate-specific antigen level ≤15ng/mL, and Gleason score ≤7. Patients with a prostate gland volume >50cm3 and baseline American Urologic Association symptom score >12 were ineligible. Patients underwent transrectal ultrasound-guided transperineal implantation of the prostate, followed by single-fraction HDR brachytherapy. Treatment was delivered using 192Ir to a dose of 19Gy prescribed to the prostate, with no additional margin applied. Of the 63 patients, 58 had data available for analysis. Five patients had withdrawn consent during the follow-up period. The median follow-up period was 2.9years (range 0.3-5.2). The median age was 61.4years. The median gland volume at treatment was 34.8cm3. Of the 58 patients, 91% had T1 disease, 71% had Gleason score ≤6 (29% with Gleason score 7), and the median pretreatment prostate-specific antigen level was 5.1ng/mL. The acute and chronic grade 2 genitourinary toxicity incidence was 12.1% and 10.3%, respectively. No grade 3 urinary toxicity occurred. No patients experienced acute rectal toxicity grade ≥2, and 2 experienced grade ≥2 chronic gastrointestinal toxicity. Three patients experienced biochemical failure, yielding a 3-year cumulative incidence estimate of 6.8%. Single-fraction HDR brachytherapy is well-tolerated, with favorable preliminary biochemical and clinical disease control rates.

Hypofractionated image guided radiation therapy followed by prostate seed implant boost for men with newly diagnosed intermediate and high risk adenocarcinoma of the prostate: Preliminary results of a phase 2 prospective study

PurposeA phase 2 protocol was designed and implemented to assess the toxicity and efficacy of hypofractionated image guided intensity modulated radiation therapy (IG-IMRT) combined with low-dose rate 103Pd prostate seed implant for treatment of localized intermediate- and high-risk adenocarcinoma of the prostate. Methods and materialsThis is a report of an interim analysis on 24 patients enrolled on an institutional review board–approved phase 2 single-institution study of patients with intermediate- and high-risk adenocarcinoma of the prostate. The median pretreatment prostate-specific antigen level was 8.15 ng/mL. The median Gleason score was 4 + 3 = 7 (range, 3 + 4 = 7 - 4 + 4 = 8), and the median T stage was T2a. Of the 24 patients, 4 (17%) were high-risk patients as defined by the National Comprehensive Cancer Network criteria, version 2016. The treatment consisted of 2465 cGy in 493 cGy/fraction of IG-IMRT to the prostate and seminal vesicles. This was followed by a 103Pd transperineal prostate implant boost (prescribed dose to 90% of the prostate volume of 100 Gy) using intraoperative planning. Five patients received neoadjuvant, concurrent, and adjuvant androgen deprivation therapy. ResultsThe median follow-up was 18 months (range, 1-42 months). The median nadir prostate-specific antigen was 0.5 ng/mL and time to nadir was 16 months. There was 1 biochemical failure associated with distant metastatic disease without local failure. Toxicity (acute or late) higher than grade 3 was not observed. There was a single instance of late grade 3 genitourinary toxicity secondary to hematuria 2 years and 7 months after radiation treatment. There were no other grade 3 gastrointestinal or genitourinary toxicities. ConclusionsEarly results on the toxicity and efficacy of the combination of hypofractionated IG-IMRT and low-dose-rate brachytherapy boost are favorable. Longer follow-up is needed to confirm safety and effectiveness.

Preoperative Statin Use at the Time of Radical Prostatectomy Is Not Associated With Biochemical Recurrence or Pathologic Upgrading

To determine the association of statin use with oncological outcomes and risk of pathologic upgrading following radical prostatectomy. Using a prospectively populated database of 3042 men who underwent open radical prostatectomy, patients were grouped according to reported statin use at the time of surgery. The primary outcome was time to biochemical recurrence. The secondary outcome was risk of pathologic upgrading among a subset of 1256 patients with Gleason pattern 3 + 3 = 6 on biopsy. A multivariable Cox model was used to assess risk of biochemical recurrence, and multivariable logistic regression was used to assess risk of pathologic upgrading. Eight hundred twenty-four men (27%) reported statin use at the time of radical prostatectomy. Statin users were older and had higher body mass index, higher Charlson Comorbidity Index, and lower pretreatment prostate-specific antigen values than statin nonusers. Over a median follow-up of 70 months (interquartile range: 36-107), a total of 455 men (15%) experienced biochemical recurrence. Statin use was not associated with biochemical recurrence (adjusted hazard ratio: 1.06, 95% confidence interval: 0.86-1.31). Of those men with biopsy Gleason 3 + 3 = 6 disease, 647 (52%) were upgraded to higher grade disease following radical prostatectomy; however, statin use was not associated with pathologic upgrading (adjusted odds ratio: 0.78, 95% confidence interval: 0.58-1.04). Preoperative statin use at the time of radical prostatectomy was not associated with biochemical recurrence or risk of pathologic upgrading in this cohort. These data add to the existing body of literature suggesting that statin use is not associated with more favorable clinical outcomes following radical prostatectomy.

Discovery of prostate specific antigen pattern to predict castration resistant prostate cancer of androgen deprivation therapy.

BackgroundProstate specific antigen (PSA) is an important biomarker to monitor the response to the treatment, but has not been fully utilized as a whole sequence. We used a longitudinal biomarker PSA to discover a new prognostic pattern that predicts castration-resistant prostate cancer (CRPC) after androgen deprivation therapy.MethodsWe transformed the longitudinal PSA into a discrete sequence, used frequent sequential pattern mining to find candidate patterns from the sequences, and selected the most predictive and informative pattern among the candidates.ResultsPatients were less likely to be CRPC if, after PSA values reach nadir, the PSA decreases more than 0.048 ng/ml during a month, and the decrease occurs again. This pattern significantly increased the accuracy of predicting CRPC by supplementing information provided by existing PSA patterns such as pretreatment PSA.ConclusionsThis result can help clinicians to stratify men by the risk of CRPC and to determine the patient that needs intensive follow-up.

High Absolute Monocyte Count Predicts Poor Clinical Outcome in Patients with Castration-Resistant Prostate Cancer Treated with Docetaxel Chemotherapy.

The association of peripheral monocyte count and prostate cancer progression is not well characterized. Our aim was to investigate the prognostic value of absolute monocyte count (AMC), which is thought to modulate immune response in the tumor microenvironment, in castration-resistant prostate cancer (CRPC) patients treated with docetaxel chemotherapy. We retrospectively reviewed the medical records of 214 CRPC patients who received docetaxel therapy and were used as the training and validation set. Docetaxel at a dose of 75 mg/m2 was administered every 3 or 4weeks. Clinicopathological factors and laboratory data were collected to assess the prognostic factors for overall survival (OS) and progression-free survival (PFS). In the training set, the median age was 73.0years, and the median prostate-specific antigen (PSA) value was 31.7 ng/ml at initial treatment. The median OS and PFS were 23.0 months (range 1.20-84.0) and 11.2 months (range 3.6-78.0), respectively. According to multivariable Cox regression analysis, AMC ≥400/uL, PSA level ≥20ng/ml, and Hb <10mg/dL were associated with increased risk of PSA progression [hazard ratio (HR) 2.06, p=0.005; HR 2.39, p=0.002; and HR2.38, p=0.024, respectively]. Moreover, multivariate analysis for OS indicated that AMC ≥400/uL, pretreatment PSA level ≥20ng/ml, presence of visceral metastasis, and alkaline phosphatase ≥284U/L were independent prognostic factors for shortened OS (HR2.07, p=0.004; HR2.18, p=0.007; HR 2.11, p=0.011; and HR 1.67, p=0.048, respectively). According to the validation set, high AMC remained an independent prognostic factor for PFS and OS (HR2.26, p=0.001; and HR3.10, p<0.001, respectively). Elevated monocyte counts were associated with aggressive tumor features and poor survival outcomes of patients with CRPC treated with docetaxel chemotherapy.

Prediction of Pathological Stage in Patients with Prostate Cancer: A Neuro-Fuzzy Model.

The prediction of cancer staging in prostate cancer is a process for estimating the likelihood that the cancer has spread before treatment is given to the patient. Although important for determining the most suitable treatment and optimal management strategy for patients, staging continues to present significant challenges to clinicians. Clinical test results such as the pre-treatment Prostate-Specific Antigen (PSA) level, the biopsy most common tumor pattern (Primary Gleason pattern) and the second most common tumor pattern (Secondary Gleason pattern) in tissue biopsies, and the clinical T stage can be used by clinicians to predict the pathological stage of cancer. However, not every patient will return abnormal results in all tests. This significantly influences the capacity to effectively predict the stage of prostate cancer. Herein we have developed a neuro-fuzzy computational intelligence model for classifying and predicting the likelihood of a patient having Organ-Confined Disease (OCD) or Extra-Prostatic Disease (ED) using a prostate cancer patient dataset obtained from The Cancer Genome Atlas (TCGA) Research Network. The system input consisted of the following variables: Primary and Secondary Gleason biopsy patterns, PSA levels, age at diagnosis, and clinical T stage. The performance of the neuro-fuzzy system was compared to other computational intelligence based approaches, namely the Artificial Neural Network, Fuzzy C-Means, Support Vector Machine, the Naive Bayes classifiers, and also the AJCC pTNM Staging Nomogram which is commonly used by clinicians. A comparison of the optimal Receiver Operating Characteristic (ROC) points that were identified using these approaches, revealed that the neuro-fuzzy system, at its optimal point, returns the largest Area Under the ROC Curve (AUC), with a low number of false positives (FPR = 0.274, TPR = 0.789, AUC = 0.812). The proposed approach is also an improvement over the AJCC pTNM Staging Nomogram (FPR = 0.032, TPR = 0.197, AUC = 0.582).