bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of decipher test on adjuvant and salvage treatments received following radical prostatectomy.
Authors: Gore John L. , Du Plessis Marguerite , Dai Darlene , Yousefi Kasra , Thompson Darby , Karsh Lawrence Ivan , Lane Brian R. , Franks Michael , Chen David , Bandyk Mark , Kibel Adam S. , Kim Hyung Lae , Lowrance William Thomas , Maroni Paul , Perrapato Scott David , Trabulsi Edouard John , Waterhouse Robert J. , Davicioni Elai , Lotan Yair , Lin Daniel W.
Published: February 2018

112

Background: Prostate cancer (PC) patients and providers have tremendous uncertainty as they decide on intervention with adjuvant or salvage radiation therapy (ART, SRT) after radical prostatectomy (RP). We prospectively evaluated the impact of Decipher test, a genomic classifier which predicts metastasis post-RP, on providers’ decision-making for ART and SRT. Methods: 150 men considering ART and 115 men considering SRT from 19 sites across the US were enrolled. Participating providers submitted a management recommendation prior to processing the Decipher test and again after receiving test results. We then followed patients for 12 months to assess actual treatment received and patient reported decisional conflict scale (DCS) and a validated survey on PC-related anxiety. Results: Pre-Decipher, observation was recommended for 89% of adjuvant men and 58% of salvage men. Post-Decipher, 17% of treatment recommendations changed in the adjuvant arm and 30% of recommendations changed in the salvage arm. Among adjuvant men, 78% maintained their recommended management 12 months after Decipher; 76% of salvage men maintained their recommended treatment after Decipher. Among 21 adjuvant men who intensified their treatment (observation to ART or ART to ART plus androgen deprivation therapy), 5 (24%) experienced biochemical recurrence with detectable PSA. In adjuvant men, PC-specific anxiety decreased differently among Decipher risk categories (p-value = 0.045), most notably among Decipher high risk men (9.07 [7.87, 10.26] pre-Decipher, 5.61 [5.35,5.88] 12 months post-Decipher). In salvage men, PC-specific anxiety decreased differently among those whose treatment were concordant (10.28 [8.1,12.47] pre-Decipher, 7.18 [6.82,7.54] 12 months post-Decipher) and those whose treatment were intensified (p-value = 0.01), and decreased differently among low-risk and high-risk Decipher patients (p = 0.04). Conclusions: Use of the Decipher test changed treatment decisions that was consistent with the eventual treatment received in three-fourths of adjuvant and salvage men after RP. Several men that pursued ART experienced PSA progression. PC-specific anxiety decreased in both adjuvant and salvage men. Clinical trial information: NCT02080689.
Ability of multiparametric magnetic resonance imaging (MRI) to predict prostate tumor heterogeneity on targeted biopsy.
Authors: Gold Samuel , Bloom Jonathan , Hale Graham R. , Rayn Kareem , Mehralivand Sherif , Wood Brad J. , Turkbey Baris , Pinto Peter A.
Published: February 2018

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Background: Prostate cancer (PCa) can show heterogeneous histology within lesions. MRI-targeted biopsy (Tbx) of the prostate improves PCa detection, but sampling within lesions has yet to be standardized. Furthermore, Tbx results are often heterogeneous as evidenced by differing histologic grades of Tbx cores within the same lesion. This introduces potential variability in biopsy results, on which clinical decisions are made. Here we aim to characterize lesion heterogeneity and identify predictive multiparametric MRI (mpMRI) features. Methods: A cohort of men who underwent mpMRI and Tbx between 2014-2017 were selected for analysis from a prospectively maintained database. To characterize lesion heterogeneity, only men with ≥2 positive Tbx cores were included. Histologic grades were scored according to International Society of Urological Pathology (ISUP) grades. Lesion heterogeneity, reported as a heterogeneity index (HI), was calculated as the difference of the average ISUP grades of Tbx cores per lesion from the maximum sampled ISUP grade of that lesion. Statistical analyses identified associations between imaging features and lesion heterogeneity. Results: 157 lesions in 114 patients met inclusion criteria. Maximum ISUP grade ranged from 1 to 5, with a median ISUP grade of 2. Higher ISUP grades were associated with greater lesion heterogeneity, HI for ISUP grade ≥3 = 0.58±0.11 vs <3 = 0.29±0.08, p = 0.0001. In addition, increasing lesion size on mpMRI was associated with greater lesion heterogeneity, HI for ≥2cm = 0.52±0.14 vs <2cm = 0.32±0.08, p = 0.0096. Finally, higher mpMRI suspicion scores were associated with increased heterogeneity vs lower suspicion scores, p = 0.048. Conclusions: mpMRI aids in characterizing PCa lesion heterogeneity to predict variability of histologic grades on Tbx. This information can assist Tbx planning to potentially reduce risks of upgrading on final pathology. Future research will examine how lesion heterogeneity can impact risk stratification and clinical decision-making for patients and practitioners. This research was supported by the Intramural Research Program of the National Cancer Institute, NIH and NIH Medical Research Scholars Program.
Outcomes of serial MRI/ultrasound fusion targeted biopsy in men with very low-risk and low-risk prostate cancer managed with active surveillance.
Authors: Hsiang Walter , Ghabili Kamyar , Syed Jamil , Nguyen Kevin , Suarez-Sarmiento Alfredo , Leapman Michael , Sprenkle Preston
Published: February 2018

114

Background: The utility of serial magnetic resonance imaging (MRI)/ultrasound (US) fusion targeted prostate biopsy in men with prostate cancer (PCa) on active surveillance (AS) have not been clearly defined. We sought to investigate the rate of Gleason upgrading both on sequential fusion targeted and systematic biopsies among men with low-risk PCa managed with AS. Methods: We retrospectively queried an institutional database of 800 patients undergoing MRI/US fusion biopsy to identify 209 patients on AS with at least two fusion biopsies between December 2013 and November 2016. Men with National Comprehensive Cancer Network (NCCN) very low-risk and low-risk criteria were included. Gleason upgrade was defined as detection of Gleason score >=3+4. The proportion of patients experiencing upgrade on systematic, fusion, or both biopsy techniques was tabulated. Associations of clinical, pathologic, and imaging factors with biopsy upgrade were analyzed by logistic regression. Results: Of 209 patients undergoing MRI/US fusion biopsy, 73 (35.0%) had at least two targeted biopsies (66% very low-risk and 34% low-risk PCa). The time between biopsies was 12.6 months (11.2-17.7). The median PSA and PSA density were 5.4 ng/mL (4.2-7.1) and 0.11 ng/mL/mL (0.07-0.18), respectively. 21 (29%) patients experienced Gleason upgrade on subsequent biopsy. Of those, 6 (8%), 5 (7%), and 10 (14%) had upgrade on systematic biopsy only, fusion biopsy only, and both systematic and fusion biopsy, respectively. Patients with upgrade on subsequent biopsy had higher PSA (p=0.02) and PSA density (p=0.02), and were among low-risk disease population (p=0.03). In logistic regression models, greater number of positive cores in systematic biopsy (OR 1.88; 95% CI 1.23-2.92; p=0.005) was associated with the total Gleason upgrade on repeated biopsy. Conclusions: In men with favorable risk prostate cancer managed with AS, Gleason upgrade was detected in a 29% of patients on a second MRI/US fusion biopsy including both targeted and systematic regions. These findings support the continued use of both MRI fusion and systematic biopsy during surveillance due to risks of reclassification over time.
Time-dependent dose distribution changes in prostate brachytherapy with iodine seeds.
Authors: Teyssier Charles , Quivrin Magali , Blanc Julie , Petitfils Aurelie , Bidault Fabienne , Cormier Luc , Chambade Damien , Martin Etienne , Crehange Gilles
Published: February 2018

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Background: Prostate brachytherapy with iodine seeds has a lasting dose delivery due to a long half life of I125 (i.e. 2 months). To assess changes in dose metrics over time in low-dose rate prostate brachytherapy with iodine seeds and its relationship with rectal distension. Methods: One hundred and twenty-one post-implant CT scans performed every 2 weeks over 2 months after the treatment procedure were analyzed for dosimetry. Each CT-scan was performed without and with rectal enema. The following rectal parameters were collected to evaluate the influence of rectal distension over time: rectal volume, cross-sectional surface area (CSA) and relative CSA calculated from the first CT-scan chosen as reference (CTref). Results: Mean V150% and V200% of the prostate volume increased significantly over time (p < 0.0001) and were significantly higher on postimplant CT scan performed at day 45 (CT45) (p = 0.024 and p = 0.003, respectively) and CT scan performed at day 60 (CT60) (p = 0.0005 and p < 0.0001, respectively) compared with CTref. All dosimetric parameters for the rectum were significantly increased over time. No rectal parameters were significantly different after rectal enema and there was no difference in doses delivered to the prostate and the rectum after rectal emptying. Conclusions: Increased hot spots in the prostate and the rectum during the 2 months following the procedure with iodine seeds may be related to prostate shrinkage rather than rectal distension. We hypothesize that radioelements with shorter half-life (Pd103 or Cs131) or HDR may give less toxicity, as dose distribution is less time-dependent.
Prediction of adverse pathology after radical prostatectomy on MPMRI in the PIRADS v2 era.
Authors: Rayn Kareem , Bloom Jonathan , Gold Samuel , Hale Graham R. , Elnabawi Youssef A , Mehralivand Sherif , Wood Brad J. , Turkbey Baris , Pinto Peter A.
Published: February 2018

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Background: As the use of MRI in the diagnosis of prostate cancer (PCa) becomes more established, knowledge of its utility as a prognostic tool is needed to better counsel patients. Here, we aim to assess the ability of mpMRI to predict adverse pathologic factors, such as extraprostatic extension (EPE), seminal vesicle invasion (SVI) or lymph node involvement (LNI) on final pathology after radical prostatectomy (RP). Methods: A prospectively maintained database was queried for all men who underwent mpMRI with current PI-RADS v2 scoring system, MRI/TRUS fusion biopsy (FBx), and RP at our institution (n = 112). Patient demographics, clinical data, imaging and pathology were recorded. Patients were stratified by presence of adverse pathology (AP), defined as EPE, SVI or LNI. Statistical analyses were used to identify mpMRI characteristics predictive of AP using STATA 13. Results: Patients with adverse pathology were middle aged, predominantly caucasian, and significantly higher PSA at baseline (Table 1). Having a PI-RADS 5 lesion was positively associated with AP (adjusted OR = 4.37, 95% CI = 1.20-15.87, p = 0.02). Mean lesion diameter on mpMRI was greater in patients with AP (p < 0.01). However, number of lesions (p = 0.12) and prostate volume on mpMRI (p = 0.88) were not associated with AP. Conclusions: The results of this study demonstrate that features on mpMRI, particularly a PI-RADS score of 5 and large lesion diameter, are predictive of adverse pathology. This information will prove valuable in developing an imaging-based prognostic model in the era of MRI and FBx. This research was supported by the Intramural Research Program of the National Cancer Institute, NIH and NIH Medical Research Scholars Program[Table: see text]
Impact of sexual orientation on contemporary rates of prostate cancer screening.
Authors: Pucheril Daniel , Ingham Matthew D. , Zlatev Dimitar V. , Berg Sebastian , Mossanen Matthew , Chang Steven Lee , Kibel Adam S. , Trinh Quoc-Dien
Published: February 2018

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Background: Despite increasing societal acceptance of non-heterosexual persons, sexual minorities continue to face discrimination. The effect of non-heterosexual orientation on adoption of cancer preventive services, particularly prostate cancer screening (PSAS), is not clearly known. We hypothesize that male sexual minorities are less likely to receive PSAS compared to heterosexual (HTS) males. Methods: The 2014-16 Behavioral Risk Factor Surveillance System was queried for males 40-69, without a history of prostate cancer, and having answered all sexual orientation (SO) questions. PSAS occurred if a respondent had a PSA test within the last two years for reasons other than “a prostate problem” or “for prostate cancer”. Descriptive statistics were generated for demographic covariates stratified by year and SO [HTS, homosexual (HMS), bisexual (BIS), transgender (TGR), other, and refused]. The Chi-Square test was used to compare the distribution of covariate proportions amongst SO categories within each year. Multivariable regression was used to determine the independent effect of SO and other covariates on receipt of PSAS in this cohort. Results: A weighted 49.2 million individuals (n = 86,893) met inclusion criteria. In 2014 and 2016, 94% and 93% of the cohort identified as HTS. In both years, a higher proportion of HMS (2014: 40.5%, 2016: 47.4) and BIS (2014: 30.3%, 2016: 31.0%) respondents were college graduates compared to HTS males (2014: 28.8%, 2016: 28.9%). In 2014, rates of PSAS were higher amongst HMS (34.9%), BIS (37.1%) and TGR (37.5%) individuals compared to HTS individuals (34.5%). In 2016, rates of PSAS were clinically similar among HTS (30.4%), HMS (30.2%), BIS (30.1%), and TGR (27.8%) individuals. In the multivariable analysis, increasing age (65-69 OR 8.93, 95%CI 7.80-10.22) and education level (College Graduate OR 2.21, 95%CI 1.93-2.54) along with insurance coverage (OR 2.15, 95%CI 1.85-2.51) and a personal physician (OR 2.88, 95%CI 2.59-3.20) were associated with higher odds of PSAS. Aside from HMS orientation (OR 1.30, 95%CI 1.04-1.62), SO was not an independent predictor of PSAS. Conclusions: Based on this nationally representative sample, disparities in regards to PSAS are not apparent for non-HTS males.
Is BMI a risk factor for active surveillance progression in patients with prostate cancer diagnosed by MRI-Trus fusion biopsy?
Authors: Rayn Kareem , Gold Samuel , Hale Graham R. , Baiocco Joey , Bloom Jonathan , Valera Vladimir , Wood Brad J. , Turkbey Baris , Pinto Peter A.
Published: February 2018

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Background: MRI−TRUS fusion biopsy (FBx) use in the diagnosis of prostate cancer (PCa) results in a more accurate assessment of disease burden and has increasingly been incorporated into urologic practice. In addition, with more men choosing active surveillance (AS) and the reports of increased PCa aggressiveness with obesity, we wanted to study the impact of obesity on the risk of PCa progression in men on AS diagnosed and followed by MRI and MRI−TRUS FBx. Methods: A retrospective review was performed on a prospectively maintained database of all men who underwent MRI−TRUS FBx at our institution from January 2007 to May 2015. Patient demographics, clinical data, imaging, pathology, treatment and outcomes were recorded. Patients who enrolled on AS were stratified by BMI into normal weight (BMI 18.5−24.9), overweight (BMI 25.0−29.9), and obese (BMI ≥ 30.0). Statistical analysis was performed using SPSS software. Results: 204 men were enrolled in AS. Within the AS cohort, 51 (25%) had a normal weight, 101 (49.5%) were overweight, and 52 (25.5%) were obese. Age, BMI, PSA and mean estimated progression free survival time are described for each of these groups in Table 1. The overall rate of progression was 32.8%. Of the patients who progressed, 18 (26.9%) were normal weight, 32 (15.7%) were overweight and 17 (25.4%) were obese. On multivariate analysis, BMI was not a risk factor for AS progression, HR = 1.00 (p = 0.99, 95% CI = 0.95−1.06). Conclusions: There is evidence of increased risk of aggressive PCa specific death in obese patients. However, we demonstrate that in patients diagnosed by FBx, obesity does not confer an additional risk of progression on AS. This may be due to the improved characterization of cancer volume and grade by MRI−TRUS fusion biopsy. Further study is required to determine risk factors for AS progression in patients undergoing FBx. This research was supported by the Intramural Research Program of the National Cancer Institute, NIH, Medical Research Scholars Program.
Validation of a genomic risk classifier to predict metastasis and prostate cancer-specific mortality in men with positive lymph nodes.
Authors: Trock Bruce J. , Karnes R. Jeffrey , Claessens Frank , Davis John W. , Haddad Zaid , Yousefi Kasra , Davicioni Elai , Ross Ashley
Published: February 2018

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Background: Men with lymph node involvement (LNI) at prostatectomy (RP) are at high risk of dying from prostate cancer. However, survival following RP is highly variable, with some men apparently cured. Nomograms developed for men with LNI have been based on series where all or the vast majority of men received adjuvant treatment. Because administration of adjuvant treatment is not universal, even for LNI, we evaluated whether the Decipher genomic classifier (GC) can improve upon clinical models to predict metastasis within 5 years (MET5) and prostate cancer specific mortality within 10 years (PCSM10) in a cohort of LNI patients, the majority of whom did not receive adjuvant treatment. Methods: 141 patients from 4 institutions (Johns Hopkins, Mayo Clinic, Leuven, MD Anderson) had LNI at RP, had adequate tissue and clinical data for analysis of MET5, and 86 were analyzed for PCSM10. 43% of men received adjuvant therapy. RP tumor tissue was analyzed by Affymetrix Human Exon 1.0 ST GeneChip; the GC was calculated based on 22 genes in the previously trained and validated algorithm. Logistic regression evaluated whether the GC, dichotomized as high risk (GC score > 0.6) vs low-intermediate risk (≤0.6), improved prediction of MET5 and PCSM10 beyond that achieved with established clinical prognostic factors. Results: 62 men (43%) developed MET5, and 35 (41%) developed PCSM10. For both MET5 and PCSM10 CAPRA-S, number of positive lymph nodes, and age were significant; adjuvant therapy was not significant. GC was a significant independent strong prognostic factor when added to the clinical model for prediction of MET5, odds ratio = 4.04 (95% CI: 1.48, 11.02), p = 0.006, and prediction of PCSM10, odds ratio = 6.71 (95% CI: 2.01, 22.38), p = 0.002. Addition of GC to the clinical model improved the AUC from 0.77 to 0.79 for MET5, and from 0.65 to 0.74 for PCSM10. Conclusions: The Decipher GC significantly improves upon clinical variables to predict metastasis and prostate cancer specific mortality in men at high risk due to LNI. This is the first study to show a genomic classifier predicts outcomes in men with LNI; validation is needed to determine if Decipher can improve treatment decisions in men with LNI.
Why are low-risk prostate cancers (PCa) treated aggressively? A population-based cohort analysis.
Authors: Basak Ramsankar , Usinger Deborah S , Godley Paul Alphonso , Chen Ronald C.
Published: February 2018

127

Background: Per AUA guidelines, active surveillance (AS) is the best option for very low-risk PCa and preferred for all low-risk patients. However, AS continues to be underused. This study examines decision-making factors in low risk patients. Methods: Using Rapid Case Ascertainment of the North Carolina (NC) Cancer Registry, 1,456 patients were enrolled from 2011-13 across NC soon after diagnosis. NCCN risk group and treatments received (or AS) were determined using medical records and registry data. Phone survey asked patients about their perceived cancer aggressiveness, most important decision-making factor (i.e., cure, quality of life, family burden, cost, daily activity), and desire to be involved in the decision process. Results: Of 585 low-risk patients, 38% pursued AS. Multivariable analysis showed that patient desire to pursue aggressive treatment and perceived cancer aggressiveness were significantly associated with aggressive treatment instead of AS (Table). Further, patients indicating primary decision was self (instead of physician) were more likely to receive aggressive treatment (Odds ratio [OR] 1.76). In the subgroup of 346 very low-risk patients, 48% received AS; patient desire for aggressive treatment and perceived aggressiveness remained significant factors. Conclusions: Patient desire for aggressive treatment and (mis)perception of cancer aggressiveness were dominant factors for low-risk patients receiving aggressive treatment instead of AS. Ascertaining patient goals for treatment and more accurate information about low-risk PCa may improve physician counseling and reduce underutilization of AS. [Table: see text]
Single-dose radiotherapy (SDRT) in the management of intermediate risk prostate cancer: Early results from a phase II randomized trial.
Authors: Greco Carlo , Pimentel Nuno , Pares Oriol , Louro Vasco , Fuks Zvi Y.
Published: February 2018

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Background: To report initial response, acute treatment-related toxicity and patient-reported quality of life (QoL) after 24Gy SDRT derived from a randomized Phase II study of patients with intermediate-risk adenocarcinoma of the prostate (NCCN definition). Methods: Between November 2015 and December 2016, 30 hormone-naïve patients were enrolled in an IRB-approved prospectively randomized phase II study to receive either 45Gy in 5 consecutive daily fractions (Hypo-SBRT) or 24Gy SDRT. Treatment was based on VMAT-IGRT with urethral sparing via a dose-painting technique and real-time motion management with beacon transponders. The PTV included the MR-delineated prostate gland and seminal vesicles with 2 mm margin. Precise PTV targeting and anatomical reproducibility was achieved via placement of an endorectal air-filled balloon (150 cc) and a Foley catheter. This setup also conferred organ motion mitigation, and online tracking ensured treatment delivery within the 2 mm PTV margin.. Genito-urinary (GU) and gastro-intestinal (GI) toxicity were graded according to the NCI CTCAE v.4, and QoL was assessed by EPIC and IPSS questionnaires. Tumor response was assessed biochemically (PSA) and by follow-up MRI at 3 months after treatment and at 6 months intervals thereafter. Results: With a median follow-up of 16 months (range, 11-24), no grade ≥2 acute GI or GU toxicities were observed in either group. There were no significant differences in mean EPIC scores in all domains. An initial 6% and 8% drop in the EPIC urinary domain score occurred in the hypo and SDRT arm respectively, returning to baselines by 3 months. . PSA reduction kinetics were similar between the two regimens, reaching ≤1 ng/mL by 18 months. Of note, all cases, regardless of treatment regimen, converted to non-detectable disease on MRI at 6 months. Patients in this trial will receive a planned 24 months post-treatment biopsy to validate treatment outcome. Conclusions: These early trial outcomes indicate that 24Gy SDRT can be consistently and safely delivered, yielding the same low acute toxicity as demonstrated with the hypo 5x9Gy schedule, and is associated with excellent QoL measures. Clinical trial information: NCT02570919.
Which patients with localized prostate cancer account for the greatest proportion of prostate cancer deaths?
Authors: Nezolosky Michelle , Nguyen Paul L. , Yang David Dewei
Published: February 2018

130

Background: We sought to determine which groups of patients, stratified by risk group and age, account for the greatest absolute number of deaths due to prostate cancer. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 437,150 men diagnosed with prostate cancer from 2004 to 2014. Men were excluded if they had N1 or M1 disease, risk group could not be determined, or if prostate cancer was not their first malignancy. Men were categorized as having low (Gleason ≤6, prostate-specific antigen [PSA] < 10 ng/mL, and cT1-T2a), intermediate (Gleason 7, PSA 10-20 ng/mL, or cT2b-T2c), or high risk disease (Gleason 8-10, PSA > 20 ng/mL, or cT3-T4). We calculated the cumulative incidence of prostate cancer-specific mortality (PCSM). Results: Median follow-up was 4.8 years. The overall incidences of diagnosis of low, intermediate, and high risk disease were 29.7% (n = 129,925), 48.0% (n = 209,643), and 22.3% (n = 97,582), respectively. 5-year PCSM for men with low, intermediate, and high risk disease was 0.5%, 1.4%, and 9.4%, respectively, and the 10-year PCSM was 1.6%, 4.0%, and 16.8%. Within 10 years of diagnosis, 6.5% (n = 905) of patients who died of prostate cancer were low risk, 27.4% (n = 3,834) were intermediate risk, and 66.2% (n = 9,278) were high risk. In particular, patients age 70 or older accounted for 49.9% of all high risk prostate cancer diagnoses, but 65.3% of deaths due to high risk prostate cancer. Conclusions: While high risk disease accounted for only 22.3% of the diagnoses, it accounted for 66.2% of the prostate cancer deaths within 10 years of diagnosis. Therefore, high risk patients account for the vast majority of prostate cancer deaths and should remain the focus of the majority of our research efforts. In addition, older patients with high risk disease die of prostate cancer at a disproportionately high rate, which runs counter to the notion that the disease is less of a threat to survival in older men.
Role of core location in targeted MRI-ultrasound fusion biopsy of prostate lesions.
Authors: Lu Amanda , Ghabili Kamyar , Nguyen Kevin , Sprenkle Preston
Published: February 2018

136

Background: Targeted mpMRI fusion biopsy has gained adoption with superior clinically significant cancer detection rates and accuracy over template biopsy. We sought to establish the role of biopsy location within a prostate lesion to detect clinically significant prostate cancer. Methods: From Nov 2016-Aug 2017, 110 patients with positive multiparametric-MRI (mpMRI) underwent targeted and systematic MRI-US fusion biopsy at our institution for clinical suspicion or known history of prostate cancer. Lesions were scored by Prostate imaging reporting and data system (PI-RADS) classification schema by experienced genitourinary radiologists. Biopsy was performed by an oncology-trained urologist (PS) performing a high volume of fusion biopsies. 5 cores were taken from each lesion, each corresponding to a predetermined location (central, medial, lateral, apex, and base of the lesion). Cancer detection rates (CDR) were calculated on a per lesion basis from biopsy histology. Results: 154 prostate lesions were identified and biopsied with an average volume of 1.31 mL. Detection of clinically significant cancer (G>3+4) did not differ significantly among the 5 locations (Table 1). The central core detected slightly more G≥3+4 cancers than the apex core. No concordance of pathology grade was found between the central core and location of the peripheral core (medial, lateral, apex, or base). In 32% (50/154) of lesions, the peripheral cores had a higher Gleason score than the central core. Biopsy of only the central core missed 40% (21/52) of G≥3+4 cancers and 17% (4/24) of G>3+4 cancers. Lesions with higher PIRADs score were more likely to detect cancer in both the central and peripheral cores, but lesion volume was not a significant predictor. Conclusions: Location of biopsy cores within mpMRI-identified prostate lesions has little correlation with detection of clinically significant cancer. However, targeted biopsy of only the center of a lesion can miss 17% of Gleason >3+4 cancers. [Table: see text]
Regulation of the tumor suppressor PLZF and prostate cancer prognosis.
Authors: Stopsack Konrad Hermann , Gerke Travis A. , Tyekucheva Svitlana , Mucci Lorelei A. , Kantoff Philip W.
Published: February 2018

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Background: PLZF ( ZBTB16) is an androgen-regulated tumor suppressor gene. Homozygous PLZF deletions are seen in a proportion of localized as well as castration-resistant prostate cancers (PC). Since PTEN has been shown to regulate PLZF expression in vitro, we hypothesized that PTEN status impacts PLZF expression in men with PC. We further hypothesized that low PLZF is associated with a poorer PC prognosis. Methods: We studied patients diagnosed with PC during prospective follow-up of the Health Professionals Follow-up Study (HPFS; n = 254) and the Physicians’ Health Study (PHS; n = 150). We performed whole transcriptome profiling of tumor specimens from cancer diagnosis and, in a subset of patients ( n = 253), a genomically-validated immunohistochemistry for PTEN. Patients were followed for metastases and PC-specific mortality (lethal cancer) after primary treatment for a median of 14 years. Univariable linear and multivariable logistic regression models for cancer outcomes, adjusted for age and calendar year, were used. For validation, the association of PTEN copy number variations and PLZF mRNA expression was assessed in The Cancer Genome Atlas (TCGA) primary PC cohort (n = 333). Results: Loss of PTEN protein expression was associated with lower PLZF expression (–0.72 standard deviations [SD]; 95% CI, –0.38 to –1.06; p < 0.001; HPFS and PHS cohorts), as were copy number variations in PTEN (TCGA cohort; –0.46 SD for deep deletions vs. diploid status; 95% CI, –0.13 to –0.79; p = 0.006) . PLZF expression did not differ significantly by Gleason grade in any cohort (all p > 0.09). In both the HPFS and PHS cohorts, the 25% of patients with the lowest PLZF expression were significantly more likely than those with higher expression to have progression to lethal cancer. This association was independent from Gleason grade, PTEN loss, and a signature of androgen receptor signaling (adjusted odds ratio for lethal cancer, 2.69; 95% CI, 1.18 to 6.14; p = 0.019). Conclusions: Loss of PTEN expression is associated with lower expression of PLZF amongst primary PC not exposed to ADT. In line with its action as a tumor suppressor, low PLZF expression is associated with lethal PC. Whether further suppression of PLZF with ADT worsens outcomes in advanced PC needs further study.
Effect of pectasol-c modified citrus pectin (P-MCP) treatment (tx) on PSA dynamics in non-metastatic biochemically relapsed prostate cancer (BRPC) patients (pts): Results of a prospective phase II study.
Authors: Keizman Daniel , Frenkel Moshe A. , Peer Avivit , Rosenbaum Eli , Margel David , Sarid David Leonid , Neiman Victoria , Gottfried Maya , Maimon Natalie , Leibovitch Ilan , Dresler Hadas , Eliaz Isaac
Published: February 2018

14

Background: 30% of pts with localized PC will have a biochemical relapse post local tx. The optimal tx of these pts remains elusive. While androgen deprivation therapy is effective in reducing PSA level, its long-term benefit on survival remain undefined, and it is associated with significant cumulative toxicities.Thus, evaluation of new non-toxic compounds in this pt population is warranted. P-MCP is a competitive inhibitor of galectin-3, a carbohydrate-binding protein, which is known to be involved in cancer pathogenesis. Pre-clinical and clinical data suggest that P-MCP is active in PC. We aimed to evaluate the safety and PSA dynamics of tx with P-MCP in pts with BRPC. Methods: Pts with non-castrate non-metastatic BRPC were enrolled in a prospective phase 2 study of tx with oral P-MCP, at 4.8 grams X 3/day for 6 months (mos). Pts that did not progress clinically, biochemically (PSA), and radiologically, at 6 mos, were treated for subsequent 12 mos. Sample size provided 85% power to assess a decrease in PSA progression rate from 80% (natural history) to 40% (P-MCP tx) at 6 mos. Results: The study was initiated in June 2013. 35 pts were enrolled. Median age was 74 years. Treatment of the primary tumor consisted of surgery in 11% (n = 4), radiation in 69% (n = 24), and both in 20% (n = 7). No pt had tx related grade 3/4 toxicity. One patient withdrew his consent after 1 mos. Of the 34 pts analyzed, 18% (n = 6) had grade 1 toxicity. 62% (n = 21) had a stabilization/decrease of PSA, and negative scans, at 6 mos, and entered the second 12 mos tx phase. A stabilization or improvement (increase) of PSA doubling time was noted in 79% (n = 27) of pts. Disease progression at 6 mos was noted in 38% (n = 13: PSA only 29%, n = 10; PSA and scans 9%, n = 3). Conclusions: The present study suggests a potential benefit of P-MCP tx on progression of BRPC. P-MCP tx is safe. Clinical trial information: NCT01681823.
When can active surveillance be less active? Prediction of long-term nonreclassification for men with low-risk prostate cancer.
Authors: Cooperberg Matthew R. , Faino Anna V , Newcomb Lisa F , Carroll Peter , Kearns James T , Brooks James D. , Fabrizio Michael , Gleave Martin , Morgan Todd Matthew , Dash Atreya , Nelson Peter , Thompson Ian Murchie , Wagner Andrew , Lin Daniel W. , Zheng Yingye
Published: February 2018

140

Background: Active surveillance is endorsed as the preferred management strategy for most men with low-risk prostate cancer. However, nearly all active surveillance protocols entail prostate specific antigen (PSA) testing every 3-6 months, and prostate biopsies every 1-2 years. For many men with indolent tumors, this regimen is overly intense, and exposes men to the discomfort, risks, and costs of repeated biopsies. We aimed to determine if some men can be safely selected for a less intense surveillance regimen by predicting the probability of non-reclassification over the next 4 years of surveillance. Methods: Data were collected from men in the multicenter Canary Prostate Active Surveillance Study (PASS), in which PSAs are collected q3 months and biopsies performed 12 months of diagnosis and then every 2 years. For inclusion in this study, men had to have undergone ≤ 1 follow up biopsy, and have Gleason grade group 1 at diagnosis. Reclassification was defined as increase in Gleason grade group on subsequent biopsy; those without reclassification were censored at last study contact, treatment or 2 years after last biopsy. A dynamic risk prediction model based on a Cox regression with robust variance estimates was used to construct and test a model predicting non-reclassification. Results: Of 1082 men included, 362 (33%) reclassified and the remaining were censored. The final regression model included percent of biopsy cores involved, prior biopsy history, time since diagnosis, BMI, prostate size, diagnostic PSA, and PSAk (a measure of PSA kinetics). This dynamic risk prediction model was assessed at a measurement time of 1 year after diagnosis, predicting risk of reclassification at 4 years. Men at lowest and highest deciles of this model-based risk faced 6% (95%CI 0-12%) and 73% (55-84%) risks of reclassification within 5 years. For at least 10% of the men in the cohort, the negative predictive value (NPV) for reclassification was 95% or higher. Conclusions: A substantial proportion of men with low-risk prostate cancer can safely be followed with a de-intensified active surveillance protocol, which would improve both the tolerability and cost-effectiveness of this management strategy.
Heterogeneity in early oncologic outcomes among men with NCCN intermediate-risk prostate cancer treated with radical prostatectomy.
Authors: Ghabili Kamyar , Nguyen Kevin , Lu Amanda , Hsiang Walter , Shuch Brian M. , Leapman Michael
Published: February 2018

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Background: The National Comprehensive Cancer Network (NCCN) risk classification scheme for prostate cancer (PCa) encompasses several definitions and has been shown to contain significant heterogeneity. Because patients possessing a single intermediate-risk (IR) feature may be regarded as ineligible for active surveillance (AS), we aimed to compare pathologic and early oncologic outcomes between those with low-risk (LR) and IR features based on the number of criteria met. Methods: We queried the National Cancer Database (NCDB) to identify men with NCCN LR (cT1-T2a, prostate-specific antigen [PSA] < 10 ng/mL, and Gleason score (GS)≤6) and IR PCa diagnosed from 2010-2014 who were treated with radical prostatectomy (RP). Patients with IR PCa were stratified based on a single factor: clinical stage (cT2b-T2c), PSA (10-20 ng/mL), GS 3+4, or GS 4+3 alone. The pathologic outcomes including any Gleason upgrade, and adverse pathology (primary Gleason 4 or ≥pT3 at RP), and receipt of adjuvant radiation therapy (RT) were compared between the LR and IR groups. Odds ratios for pathologic outcomes and receipt of adjuvant RT were computed using logistic regression analyses. Results: Of 181,847 men treated with RP, we identified 30.7% and 37.1% with LR and IR PCa, respectively. Of 67,623 with IR PCa, 4,075 (6%) were due to clinical stage alone, 5,004 (7.4%) by PSA, 43,409 (64.2%) by GS 3+4, and 15,135 (22.4%) by GS 4+3. Patients meeting IR by clinical stage alone had similar risks of adverse pathology as LR patients (OR 1.03, 95%CI 0.94-1.13, p = 0.49). In contrast, those meeting IR by PSA alone had higher risks of adverse pathology compared with LR individuals (OR 2.20, 95%CI 2.05-2.36, p < 0.001). Moreover, receipt of adjuvant RT was similar among LR and IR patients by clinical stage alone (p = 0.62), and higher among patients meeting IR by PSA alone (OR 2.99, 95% CI 2.43-3.69, p < 0.001). Conclusions: Based on national cancer registry data, early outcomes among men meeting the NCCN IR definition for PCa are heterogeneous. IR patients by clinical stage alone had similar rates of adverse pathology as did LR group. Broadened eligibility for AS should be considered to include those meeting favorable IR definitions.
Comparative effectiveness of a patient-centered prostate biopsy report in clinical prostate cancer practice.
Authors: Nayak Jasmir G. , Scalzo Nicholas , Chu Alice , Dy Geolani , Macleod Liam Connor , Kearns James T , Mossanen Matthew , Ellis William J. , Lin Daniel W. , True Lawrence D. , Gore John L.
Published: February 2018

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Background: The prostate biopsy pathology report is a critical decision-making document for men newly-diagnosed with prostate cancer, yet the content may be beyond the health literacy of most patients. We compare the effectiveness of a patient-centered prostate biopsy report developed through patient-centered outcomes research methods with standard synoptic reports. Methods: Using a modified Delphi approach, a multidisciplinary group of prostate cancer experts provided consensus for the critical components of a prostate biopsy report for treatment decision-making. Patient focus groups provided input for syntax and formatting to inform the design of a patient-centered pathology report. 94 patients with recent prostate biopsies were block randomized to receive the standard report with or without the patient-centered report. We evaluated patient self-efficacy, provider communication and empathy, and prostate cancer knowledge at pathology disclosure. We compared study groups with descriptive statistics. Results: Experts selected primary and secondary Gleason score and number of positive cores as the important elements of a prostate biopsy report. Patients prioritized a narrative word structure, clear language, a tabular format for histologic grade, and information on risk classification. Initial assessments were completed by 84% (79/94) of participants including 40/46 in the standard report group and 39/48 in the patient-centered report group. Patients who received the patient-centered report had significantly improved ability to recall their Gleason score (100% vs. 85%, p = 0.03) and number of positive cores (90% vs. 65%, p = 0.01). Provider communication and patient self-efficacy were uniformly high and did not differ between groups. 88% of patients who received the patient-centered report felt that it helped them better understand their pathology results. Conclusions: A patient-centered prostate biopsy pathology report is associated with significantly higher knowledge about a new prostate cancer diagnosis. These health information documents may help facilitate shared decision-making among patients newly diagnosed with prostate cancer.
Bladder filling during radiation therapy for prostate cancer treatment: Assessment via bladder ultrasound scanner.
Authors: Waddle Mark Raymond , Landy Robin , Ryan Karen , Tzou Katherine S. , Stross William C , Kaleem Tasneem , Miller Daniel , Trifiletti Daniel Michael , Herchko Steven , Serago Christopher , Buskirk Steven J.
Published: February 2018

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Background: Prostate cancer patients treated with external beam radiation therapy are instructed to present daily with a full bladder to decrease small bowel and bladder toxicity and to increase reproducibility of treatment. However, older patients may have difficulty presenting with full bladders and variation of bladder volume with treatment is unknown. The objective of this study was to assess bladder filling at the time of radiation treatment (RT) using a bladder ultrasound in patients undergoing treatment for prostate cancer. Methods: Patients with prostate cancer were prospectively enrolled prior to CT simulation from January to August 2017. Bladder volume was recorded during CT simulation and daily immediately prior to RT. Patients were instructed to drink 8-12 ounces of water 30-60 minutes prior to RT. Three bladder volume measurements were recorded daily and averaged at the time of each treatment. Average bladder volume during treatment and the number of treatments with low bladder volumes ( < 50cc, < 60cc, and < 100cc) were reported using descriptive statistics. Results: A total of 13 patients completed a median of 42 days of RT during the study period, resulting in 550 daily bladder volumes. Ten patients were treated definitively and 3 with salvage radiation after prostatectomy. The median age of patients in the study was 72 years. Older patients were statistically more likely to present with low bladder volumes, with percentage of treatments with a bladder volume less than 50cc, 60cc, and 100cc being 29%, 42%, and 66% compared to only 4%, 7%, and 18% in patients aged < 70 (P < 0.01). The average bladder volume at the time of CT simulation was 176cc ± 57cc and the average volume during treatment was 140cc± 93cc, which was not statistically different (P = 0.28). The bladder volume did not significantly change over the course of treatment. Conclusions: Older patients (age 70+) with prostate cancer were more likely to present for RT with low bladder volumes in this prospective study. Our findings suggest that older patients should receive extra counseling about bladder filling and/or may require less bladder filling at the time of CT simulation to provide more accurate bowel dosimetry measurements.
Association of changes in functional status with radiation for prostate cancer in older veterans.
Authors: Ursem Carling Jade , Diaz-Ramirez L. Griselle , Lang-Brown Sean , Wei Xiao X. , Chen Ronald C. , Lee Sei
Published: February 2018

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Background: Although radiation therapy (RT) for prostate cancer is generally well tolerated, frail older adults with less functional reserve may experience more toxicity and loss of independence. Our objective was to determine trajectories of activities of daily living (ADL) for prostate cancer patients admitted to a nursing home for RT. Methods: We used the Veterans Affairs (VA) Minimum Data Set (MDS) to identify men age ≥65 with an ICD9 diagnosis of prostate cancer living in a VA nursing facility (CLC) 1/2005-12/2015, an MDS evaluation reporting RT and no ICD9 code for bone metastasis. Functional status was assessed using MDS-ADL score (range 0-28, higher scores = greater disability). A piecewise linear mixed effects model (nodes at months 1 and 3) modeled the relationship between baseline characteristics and MDS-ADL score. Results: 645 patients were identified, of whom 585 (90.7%) had not resided in a CLC prior to RT. Median age 74 (range 65-94), median baseline PSA 5.33 ng/mL (IQR 1-14.57), and median Charlson Comorbidity Index (CCI) 5 (30.5% CCl ≥8). Baseline median MDS-ADL score was 1 (range 0-28). Patients with CCI 2-3 did not have appreciable change in functional status in 6 months following start of RT, while patients with CCI 4-7 had an increase months 1-3, followed by improvement (Table). Compared to patients with CCI 2-3, those with CCl ≥8 had an increase in MDS-ADL score of 1.8 points/month months 1-3 after starting RT (p = 0.008), and increase in MDS-ADL score of 3 points/month from 3 months onward (p < 0.001). Older age and higher CCI were associated with increase in MDS-ADL score (p < 0.05). Conclusions: In a cohort of elderly prostate cancer patients with significant comorbidity, RT led to different functional trajectories depending on comorbidity burden. While patients with moderate comorbidity had an initial decline in functional status followed by improvement, patients with high comorbidity had continued functional decline. [Table: see text]
Association of low PTEN expression by fluorescence immunohistochemistry (F-IHC) and lethal disease in men with surgically-treated prostate cancer (PrCa).
Authors: Hamid Anis , Gray Kathryn P. , Huang Ying , Bowden Michaela , Loda Massimo , Pomerantz Mark , Sweeney Christopher
Published: February 2018

15

Background: Loss of PTEN expression correlates with poorer clinical outcomes after definitive therapy for non-metastatic (M0) PrCa. While most studies have used biochemical-based end points, there is limited data regarding PTEN loss by IHC and risk of lethal disease after surgery. Methods: A retrospective cohort of patients who underwent radical prostatectomy (RP) was identified from the Dana-Farber Prostate Clinical Research Information Systems (CRIS) database. Formalin-fixed, paraffin-embedded RP specimens were used to construct tissue microarrays and F-IHC for PTEN was performed. Using multispectral imaging analysis, tumor-only PTEN expression was quantified. PTEN expression was analyzed continuously and dichotomously (low [ < lower quartile] vs other [≥lower quartile]). Kaplan-Meier method estimated the distribution of time from RP to metastatic disease and overall survival (OS). Cox model assessed association of PTEN status and the disease outcomes, with adjustment of age, Gleason score and pathological stage in multivariate analyses (MVA). Prognostic ability of PTEN was also explored using a logistic regression model. Results: The analysis cohort comprised 91 patients with either non-lethal (no metastatic or biochemical relapse) or lethal disease (metastasis post-RP). The median follow-up was 12.4 years. PTEN low was significantly associated with lethal disease as both a continuous (HR 1.82, 95% CI 1.35-2.44) and dichotomous (HR 2.94, 95% CI 1.52-5.56) variable. Significant association of PTEN-low expression and poorer OS was observed (cont: HR 2.22, 95% CI 1.54-3.23; low vs other: HR 4.00, 95% CI 1.89-8.33). MVA models yielded consistent results. A prognostic model assessing 10-year disease outcomes showed incremental prognostic improvement with PTEN status added to age/Gleason/stage (lethal disease: area under curve (AUC) 0.79 vs 0.84 [+PTEN status]; death: AUC 0.71 vs 0.76 [+PTEN status]). Conclusions: Low PTEN expression by F-IHC in primary prostate cancer is an independent prognostic biomarker of lethal disease and death after surgery. Quantitative F-IHC for PTEN is a viable diagnostic assay in this context.