Risk Localized Prostate Cancer Research Articles

Use of PSMA PET/CT to detect prostate cancer metastatic to a preexisting thyroid nodule

Prostate cancer (PCa) seldom metastasizes to the thyroid gland, and only a limited number of cases are documented in the literature. The application of a relatively recent and highly sensitive imaging technique, prostate-specific membrane antigen (PSMA) positron emission tomography—computed tomography (PET/CT), has enhanced the identification of metastatic disease. Nevertheless, as PSMA is expressed in various tissue types, the clinical importance of a PSMA-avid thyroid lesion remains largely uncertain. A minor, yet noteworthy, percentage of these lesions are ultimately determined to be malignant. Here we describe the case of a 70-year-old man with a past medical history of Lynch syndrome who presented to an outpatient oncologic clinic for management of very high risk localized PCa. He developed metastatic recurrence and his disease progressed through several lines of therapy, including immunotherapy and targeted treatments. He was found to have a new, intense PSMA uptake in an existing, previously benign thyroid nodule. Sonographic evaluation revealed changing morphology despite grossly stable size. Repeat biopsy confirmed the unusual finding of PCa metastasis to a known thyroid nodule. The shift in PSMA avidity played a pivotal role in discerning this metastatic deposit. There is a potential risk that such lesions may be inadequately acknowledged. The impact of the patient’s Lynch syndrome on this presentation remains uncertain.

Untreated hypogonadism and testosterone replacement therapy in hypogonadal men are associated with a decreased risk of subsequent prostate cancer: a population-based study.

We sought to understand the relationship between hypogonadism and testosterone replacement therapy (TRT) in hypogonadal men on the risk of developing localized and metastatic prostate cancer. We used the Merative MarketScan database of commercial claims encounters to identify men diagnosed with hypogonadism. These men were matched to eugonadal men who served as controls. Multivariate negative binomial regression analysis of prostate cancer diagnoses, hypogonadism, and TRT in hypogonadal men adjusting for various known confounding factors was used to understand the impact of hypogonadism and TRT on prostate cancer risk. We identified 3,222,904 men who met inclusion criteria, of which 50% were diagnosed with hypogonadism (1,611,452) and each were matched to a control (1,611,452). The incidence of prostate cancer was 2.16%, 1.55%, and 1.99% in eugonadal controls, hypogonadal men on TRT, and hypogonadal men without TRT, respectively (p < 0.001). Untreated hypogonadism was independently associated with a decreased risk of localized prostate cancer (IRR 0.46, 95% CI 0.43-0.50, p < 0.001) compared to eugonadal controls. Hypogonadal men on TRT also had a significantly decreased risk of localized prostate cancer (IRR 0.49, 95% CI 0.45-0.53, p < 0.001). Furthermore, hypogonadal men on TRT (IRR 0.21, 95% CI 0.19-0.24, p < 0.001) or without TRT (IRR 0.20, 95% CI 0.18-0.22, p < 0.001) both had significantly decreased risk of metastatic prostate cancer, respectively. Our population-based analysis suggests that untreated hypogonadism in men is associated with a 50% decreased incidence of localized prostate cancer and an 80% decreased incidence of metastatic prostate cancer. TRT in hypogonadal men was also associated with a decreased risk of subsequent prostate cancer. Further research is needed to better understand the relationship between hypogonadism and TRT in hypogonadal men on the riskof subsequent prostate cancer.

Real world US community urology adherence to prostate cancer guidelines.

449 Background: According to a 2010 Surveillance, Epidemiology, and End Results (SEER) Medicare analysis of prostate cancer (PCa) patients between 1992 and 2005, urologists accounted for more health services provided to PCa patients than any other specialty. Our study assessed the concordance of PCa care with two treatment-related Performance Indicators (PIs) derived from National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines) in a real-world setting of community urologists. Methods: This retrospective analysis used PPS Analytics (Specialty Networks) Patient Population Health Management Platform, capturing 90 community urology practices with approximately 539,000 PCa patients treated between 7/1/2019-6/30/2022. Two PIs were identified from NCCN Guidelines through consultation with expert urologists to measure the quality of PCa care. PI-1 was defined as the proportion mCSPC patients who initiated an NCCN Category 1 preferred regimen for mCSPC. Guideline changes on 01/01/2020 created a need for two patient stratifications in PI-1. Patients in PI-1.1 had a mCSPC diagnosis between 05/2002 - 12/2019. Patients in PI-1.2 had a mCSPC diagnosis between 01/2020 - 06/2021. PI-2 was defined as the proportion of newly diagnosed intermediate-to-high risk localized PCa (Gleason score ≥ 7 or PSA ≥ 10) who received concurrent ADT with external beam radiation therapy (EBRT) based on the NCCN Guidelines recommendation for concurrent ADT in newly diagnosed intermediate-to-high risk localized PCa (LPC) receiving EBRT. Multi-level multi-variable regression was used to assess factors associated with concordance for each PI. Results: See table. Conclusions: Although changes in NCCN guidelines after 1/2020 led to improved systemic treatment in mCSPC, most patients still did not receive care concordant with recent NCCN recommendations. Our findings highlight opportunities for improving the quality of PCa care in a real-world community urology setting, notably for treatment in mCSPC. Future research should investigate reasons for deviating from NCCN preferred systemic regimens in mCSPC and intervene as appropriate.[Table: see text]

Real-world clinical outcomes of patients with localized prostate cancer (LPC) treated with external beam radiation therapy (EBRT).

330 Background: Patients (pts) with localized prostate cancer (LPC) or locally advanced prostate cancer (PC) have several treatment options, including external beam radiation therapy (EBRT) and radical prostatectomy, which can be curative in some pts. However, limited real-world evidence exists on the long-term clinical outcomes of these pts, particularly those with high-risk LPC (HRLPC). This study examines real-world clinical outcomes for HRLPC and low/intermediate risk LPC (LIRLPC) pts treated with EBRT in the US. Methods: A retrospective study using Surveillance, Epidemiology, and End Results (SEER)-Medicare linked registry-claims data from 2012−2019 included LPC pts aged ≥65 treated with EBRT as initial definitive therapy. Baseline demographic and clinical characteristics were summarized for HRLPC and LIRLPC pts. Clinical outcomes of interest (overall survival, metastasis-free survival [MFS] and time to initiation of advanced PC treatment) were compared using Kaplan-Meier (KM) and Cox proportional hazards (PH) models. Results: Of 11,127 LPC pts treated with EBRT within 6 months of LPC diagnosis, ~40% (n=4,414) were HRLPC and ~60% (N=6,713) were LIRLPC. Patient characteristics for both groups appeared similar, with mean age at EBRT initiation &gt;70 years, 86% white, and mean follow-up time &gt;40 months. ADT was used with EBRT in 78% HRLPC and 34% LIRLPC. Median (IQR) duration of ADT therapy (via KM analysis) was 9.9 (5.8, 21.5) months for HRLPC and 7.2 (5.3, 9.8) months for LIRLPC. A higher proportion of HRLPC vs LIRLPC pts experienced metastasis, death, and progression to advanced PC therapies (medians were not reached). Unadjusted Cox PH survival analyses showed higher risk of mortality, metastasis, and advanced PC therapy use for HRLPC vs LIRLPC pts. Conclusions: This real-world study of clinical outcomes in pts with HRLPC and LIRLPC treated with EBRT suggested substantial additional disease burden in pts with HRLPC and highlights the need for additional strategies and treatments to improve clinical outcomes in pts with HRLPC. [Table: see text]

Cryotherapy As Treatment of Curative Intent for Localized Adenocarcinoma of The Prostate Gland with A Focus on Low-risk and Medium – (Intermediate-) Risk Localized Adenocarcinoma of The Prostate Gland: A Review and Update

Cryotherapy As Treatment of Curative Intent for Localized Adenocarcinoma of The Prostate Gland with A Focus on Low-risk and Medium – (Intermediate-) Risk Localized Adenocarcinoma of The Prostate Gland: A Review and Update

Impact of clinical staging based on DRE versus imaging (TRUS/MRI) in localized prostate cancer risk assessment.

227 Background: The Cancer of the Prostate Risk Assessment (CAPRA) score is a validated risk assessment tool for biochemical recurrence (BCR) risk after radical prostatectomy (RP) for localized prostate cancer. The score is calculated using five clinical variables: age, PSA at diagnosis, Gleason score pattern, percentage of positive biopsy cores, and clinical stage by digital rectal exam (DRE). Since its publication in 2005, transrectal ultrasonography (TRUS) and magnetic resonance imaging (MRI) have increasingly been used in clinical evaluation but have yet to be integrated into prostate cancer tumor staging rules or risk-stratification models. We incorporated both clinical- and imaging-derived stage into the CAPRA score to assess the association between the base and imaging-adjusted CAPRA model and the outcome of BCR. Methods: We performed a retrospective analysis of patients who underwent RP for prostate cancer staged ≤T3a on both DRE and imaging (TRUS/MRI) and diagnosed between 2000-2017 at our institution. DRE was treated as a binary variable (T1 vs ≥T2) as was imaging (≤T2 vs T3a). BCR was defined as 2 consecutive PSA ≥0.2 ng/ml starting 8 weeks post-surgery or receipt of salvage treatment. Two CAPRA scores were computed: one with DRE-derived and one with image-based T-stage. Life table estimates were used to evaluate likelihood of BCR-free survival after RP stratified by CAPRA scores. We performed Cox regression to examine the association between clinical CAPRA components and BCR risk and to determine whether stratifying clinical T1, T2, and T3a disease in CAPRA was independently associated with BCR risk on multivariate analysis. Results: Of 1972 patients studied, 103 (5%) had upstaging in CAPRA risk group with imaging-reported clinical stage. Life table estimates were comparable between DRE- and imaging-based CAPRA score with regard to likelihood of BCR-free survival. In separate unadjusted Cox regression models, DRE-based (HR 1.57; 95% CI 1.50-1.64) and imaging-based clinical CAPRA (HR 1.56; 95% CI 1.50-1.63) were both independently associated with risk of recurrence after RP and model fit did not differ significantly. On multivariable Cox regression adjusted for CAPRA component variables, clinical stage ≥T2 on DRE (HR 1.28; 95% CI 1.06-1.54) and T3a on imaging (HR 1.79; 95% CI 1.47-2.19) were independently associated with BCR risk. Conclusions: Both DRE- and imaging-based clinical CAPRA nomograms are associated with risk of BCR after RP for prostate cancer. On multivariable analysis, both modalities of clinical staging are independently associated with CAPRA score on the risk assessment nomogram. Each staging modality offers independent prognostic information, which supports the continued use of DRE-based clinical staging in prostate cancer risk stratification and demonstrates the potential benefit imaging-based clinical stage may add to these models and to tumor staging standards.

Pelvic lymph node dissection in high-risk prostate cancer.

ABSTRACTIntroduction:The therapeutic role of pelvic lymph node dissection (PLND) in prostate cancer (PCa) is unknown due to absence of randomized trials.Objective:to present a critical review on the therapeutic benefits of PLND in high risk localized PCa patients.Materials and Methods:A search of the literature on PLND was performed using PubMed, Cochrane, and Medline database. Articles obtained regarding diagnostic imaging and sentinel lymph node dissection, PLND extension, impact of PLND on survival, PLND in node positive “only” disease and PLND surgical risks were critically reviewed.Results:High-risk PCa commonly develops metastases. In these patients, the possibility of presenting lymph node disease is high. Thus, extended PLND during radical prostatectomy may be recommended in selected patients with localized high-risk PCa for both accurate staging and therapeutic intent. Although recent advances in detecting patients with lymph node involvement (LNI) with novel imaging and sentinel node dissection, extended PLND continues to be the most accurate method to stage lymph node disease, which may be related to the number of nodes removed. However, extended PLND increases surgical time, with potential impact on perioperative complications, hospital length of stay, rehospitalization and healthcare costs. Controversy persists on its therapeutic benefit, particularly in patients with high node burden.Conclusion:The impact of PLND on biochemical recurrence and PCa survival is unclear yet. Selection of patients may benefit from extended PLND but the challenge remains to identify them accurately. Only prospective randomized study would answer the precise role of PLND in high-risk pelvis confined PCa patients.

SP-0053 LDR prostate brachytherapy is safe and effective for all localized prostate cancer risk groups

SP-0053 LDR prostate brachytherapy is safe and effective for all localized prostate cancer risk groups

Preoperative predictors of biochemical recurrence in a phase II trial of neoadjuvant therapy in very high-risk prostate cancer.

74 Background: Understanding the lethal nature of high risk prostate cancer, there is a need for the development of multimodal therapies. Prior studies have confirmed a survival benefit with the addition of docetaxel to androgen deprivation therapy (ADT) in men with metastatic hormone-sensitive prostate cancer (HSPC). We conducted a Phase II trial enrolling men with very high risk localized, locally advanced or oligometastatic prostate cancer (PC) to examine resistance and response to neoadjuvant chemohormonal therapy. This analysis aims to identify the preoperative predictors of biochemical recurrence (BCR). Methods: UW17009 is an IRB-approved open-label, single-arm trial that recruited 26 men with newly diagnosed advanced PC. Patients received ADT and docetaxel for 3 months followed by prostatectomy. The primary endpoint was pathologic complete response rate. A secondary clinical objective was the rate of PSA recurrence 12 months after surgery. The pre-trial PSAs, age, cancer grade, stage, percent tumor involvement of the initial biopsy, metastatic disease on conventional and 18F-DCFPyL PSMA (DCFPyL) PET/CT and MRI imaging, completion of chemohormonal therapy and PSA nadirs following chemohormonal therapy were assessed in relationship to biochemical recurrence. One way ANOVA was used to evaluate differences among continuous values: age, PSA at diagnosis, percent tumor involvement, and PSA nadir after chemo ADT. Fisher’s exact tests were used to evaluate the differences among categorical variables: stage at diagnosis, positive bone scan, and positive PSMA PET. Results: 26 patients were enrolled and underwent neoadjuvant treatment, radical prostatectomy (RP) and lymph node dissection. The median age was 62 (IQR 58-66), mean PSA at diagnosis was 32.8 ng/dl and 88.4% had Gleason 9 cancer. At study initiation, 12/26 patients had metastatic disease detected by DCFPyL-based PSMA PET. Final pathology demonstrated 81%(21/26) had ≥ pT3 and 73%(19/26) patients had negative margins. Positive lymph nodes were found in 10/26(38.5%) patients on final pathology. At week 6 after surgery, 91%(24/26) had undetectable PSA. At a mean follow up of 12.1 months(5.2-21.4), the biochemical recurrence rate is 58%(15/26). Features associated with BCR include stage, % tumor involvement, and positive PSMA PET scan. All patients with positive margins and 9/10 patients with positive nodes at final pathology developed BCR at a mean follow up of 12 months. Conclusions: In this neoadjuvant cohort, stage T2c, elevated PSA, positive pre-operative PSMA PET/CT, and PSA nadir &gt; 1 following chemohormonal therapy predict biochemical recurrence. Clinically, and in the short term, neoadjuvant chemohormonal therapy prior to definitive surgery for very high risk localized and/or oligometastatic PC generates local tumor control with a high rate of negative surgical margins.

Timing of high-dose rate brachytherapy with external beam radiotherapy in intermediate and high-risk localized prostate cancer (THEPCA) patients and its effects on toxicity and quality of life: Results of a randomized feasibility trial.

236 Background: Advances in brachytherapy, external beam radiotherapy (EBRT) and image-guided radiotherapy have revolutionized radiotherapy delivery. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities remain a significant issue. Currently there is no European consensus on the timing of high-dose rate (HDR) brachytherapy in relation to EBRT. Schedules of HDR boost before or after EBRT vary significantly between institutions.The incidence of GI and GU toxicities was assessed in patients receiving HDR brachytherapy before and after EBRT. Methods: Men with Intermediate/high risk localized prostate cancer were randomized to Arm A (HDR brachytherapy before EBRT) or Arm B (HDR brachytherapy after EBRT). Both arms received a HDR boost of 15Gy and 46Gy in 23 fractions of EBRT. All patients received neoadjuvant and adjuvant hormone therapy for up to 2 years. Patients were followed quarterly up to a year. CTCAE scores for GU and GI toxicities were taken. IPSS, IEFL and FACT-P scores were collected. Fisher’s exact test was used to analyze the association between GU and GI toxicities. The T-test compared the mean differences in IPSS total scores at each follow-up. Analysis of variance evaluated the difference at follow up. Post-hoc testing and Bonferroni correction was applied. Results: 100 patients were randomized between 2015 and 2017. Data for 88 patients was available at cutoff. Mean age was 69 years (SD: 4.6). Age, Gleason score, TNM and clinical staging were similar in each arm. Mean IPSS Score was similar between both arms at baseline Arm A (6.52) &amp; Arm B (6.57). 12 months follow up showed mild worsening of symptoms in both arms, but no significant difference noticed between Arm A (8.02) &amp; Arm B (8.14) p=0.55. At 12 months, Grade 1 and 2 GU toxicities were more frequent in Arm A (22.88% &amp; 5.28%, p=0.669) compared to Arm B (19.36% and 2.64%, p=0.485). Grade 1 GI toxicity was more common in Arm B (23.76%) than Arm A (21.2%), p=0.396. Grade 2 GI toxicities were more common in Arm A 5.28% vs 3.52%, p=0.739. Baseline mean IIEF scores were 10.9 and 10.53 in Arm A and B respectively. At 12 months this was 6.6 in Arm A and 7.11 in Arm B, but not statistically significant. FACT-P scores were not different in either arm, with good QOL scores maintained throughout. Mean score at baseline (125.18) was observed to be similar at 12 months follow up at (126.10). The PTV, CTV &amp; OAR dose were compared and no significant differences were found. Conclusions: There were no significant differences in GI and GU related toxicities up to a year between patients receiving HDR brachytherapy before or after EBRT. There were no grade 3 or 4 toxicities. Treatment was well tolerated in both arms with good QOL scores. Longer follow up and a phase III multicenter RCT would be needed to validate findings. Clinical trial information: NCT02618161.

The stereotactic prostate radiotherapy (SPORT) trial: A randomized feasibility study comparing prostate SABR to prostate and pelvic nodal SABR.

248 Background: Stereotactic Ablative Radiotherapy (SABR) is increasingly used to treat low/intermediate risk localised prostate cancer (PCa). However, data on SABR +/- pelvic nodal irradiation (PNI) in high-risk disease is limited to single institution, single-arm studies. The Stereotactic Prostate Radiotherapy (SPORT) trial examined the feasibility of delivering a randomised trial of SABR ± PNI. The composite primary endpoint to determine feasibility comprised: recruitment rate, technical feasibility, acute toxicity (CTCAE v4.0) and quality of life (QoL)(EPIC). Secondary and exploratory endpoints including late toxicity (RTOG) and QoL and potential biomarkers of toxicity (plasma citrulline and DNA damage in circulating lymphocytes) are also presented. Methods: Men with localised PCa demonstrating one of T3a, Gleason score ≥4+3 or PSA&gt;20 were eligible. T3b and T4 disease were excluded. 30 participants were randomised 1:1 to prostate SABR (P-SABR) or prostate and pelvis SABR (PPN-SABR). The prostate and proximal 1-2cm seminal vesicles received 36.25 Gy in 5 fractions over 29 days (prostate CTV 40Gy). The PPN-SABR arm also received 25 Gy in 5 fractions to the pelvic nodes. All patients had fiducial markers and a rectal spacer gel in-situ. As initial toxicity rates were low, the final 10 men received an additional integrated boost to the dominant intraprostatic lesion of up to 50 Gy, irrespective of randomisation. Results: Feasibility was demonstrated. The target recruitment of 30 men was met (83% high risk). Treatment, including an integrated boost plus PNI, was achievable using strict normal tissue constraints. Acute toxicity and QoL were acceptable (Table: Grade≥2 GU 7%, 27% and GI 0%, 7%; minimal clinically important change (MCIC) in EPIC urinary 40%, 60% and bowel score 33%, 47% in P and PPN arms respectively). At median follow up of 30 months (range 18-42 months), late toxicity and QoL were acceptable (Grade≥2 GU 7%, 20% and GI 0%, 13%; MCIC in EPIC urinary 33%, 67% and bowel score 33%, 67% in P and PPN arms respectively). All toxicity was ≤ grade 2 with the exception of one late grade 3 GU toxicity occurring in the PPN arm. Serum citrulline, a marker of small bowel function, trended towards lower levels in the PPN arm, in keeping with a significantly higher dose delivered to the small bowel in this arm. DNA damage foci in circulating lymphocytes increased at 1 hour after radiation. Foci count and repair correlated to toxicity measures will be presented. Conclusions: A randomised clinical trial comparing P-SABR to PPN-SABR is feasible. There was a suggestion of increased toxicity with PPN-SABR, but this remained acceptable. This data will inform a UK multi-centre phase 2 study. Clinical trial information: NCT03253978 . [Table: see text]

Expanding indication of padeliporfin (WST11) vascular-targeted photodynamic therapy: Results of prostate cancer Latin-American multicenter study

ObjectivesTo explore the proportion of patients with higher risk localized prostate cancer (PCa) that would become safely biopsy negative 12 months after non-thermal focal therapy with padeliporfin vascular-targeted photodynamic therapy (VTP). MethodsMulticenter study in a scenario of prostate-specific antigen (PSA)≤20ng/ml and variable PCa target volumes Gleason pattern 3 or low-volume secondary Gleason pattern 4, all patients received VTP, consisting of intravenous 4mg/kg padeliporfin activated by light-diffusing fibers in the prostate. The prostate was biopsied at baseline, months 6 and 12, PSA, patient-reported functional outcomes and quality of life (QoL) questionnaires were recorded at baseline, months 3, 6, and 12 and adverse events (AE) throughout the study. ResultsIn the intention-to-treat population (n=81), the proportion of patients with negative biopsies at month 12 was 74% (60/81 patients; 95% CI: 63.1%, 83.2%). In the per-protocol population, the proportion was 79% (58/73 patients; 95% CI: 68.4%, 88.0%). Questionnaire results indicated a slight improvement in urinary function and limited deterioration in sexual function. No difference in QoL was observed over time. A total of 42/81 (52%) patients reported mild or moderate and 4 of 81 (4.9%) experienced serious AE, all resolved without sequelae. No phototoxicity, cardiovascular event, fistula or prolonged urinary incontinence, secondary cancer or death was reported. ConclusionsResults support the efficacy, safety, and QoL associated with padeliporfin focal treatment for low/intermediate risk localized PCa.

Traitement focal par HIFU versus prostatectomie radicale robot-assistée pour cancer de la prostate localisé : résultats carcinologiques et fonctionnels à 1 an

To analyse the functional and oncologic outcomes at one year of focal therapy with HIFU compared with total prostatectomy in patients with localised prostate cancer (PCa). Retrospective and monocentric study from 2008 to 2014 comparing 2 cohorts of patients with localised PCa (T1/T2 clinical stage, Gleason score≤3+4=7 and PSA<15ng/mL), one treated by focal therapy (HIFU-F group), one by robot-assisted total prostatectomy (RATP group). Primary outcome was a trifecta defined as: absence of urinary incontinence, erectile function with sexual relations without treatment, negative PSA with negative surgical margins (RATP group) or negative biopsy cores (HIFU-F group). The 53 patients included in the "HIFU-F" group and the 66 patients in the "RATP" group were similar in terms of preoperative PSA, D'Amico risk group, erectile function but were different in terms of age, prostatic volume, length of cancer, Gleason score. Complication rate was not different. In multivariate analyse with propensity score, "HIFU-F" group achieved a better trifecta score than "RATP" group (OR=8,3, p=0,005). In case of low or intermediate risk localised PCa, "HIFU-F" group had better functional outcomes than initial learning curse "RATP" group, at one year. A long-term evaluation by a common endpoint is necessary to judge the oncological equivalence of both techniques. 3.

Impact of individual and neighborhood factors on socioeconomic disparities in localized and advanced prostate cancer risk.

The reasons behind socio-economic disparities in prostate cancer incidence remain unclear. We tested the hypothesis that individual-level factors act jointly with neighborhood-level social and built environment factors to influence prostate cancer risk and that specific social and built environment factors contribute to socio-econmic differences in risk. We used multi-level data, combining individual-level data (including education and known prostate cancer risk factors) for prostate cancer cases (n = 775) and controls (n = 542) from the San Francisco Bay Area Prostate Cancer Study, a population-based case-control study, with contextual-level data on neighborhood socio-economic status (nSES) and specific social and built environment factors from the California Neighborhoods Data System. Multivariable logistic regression models were used to compute adjusted odds ratios separately for localized and advanced stage prostate cancer while controlling for neighborhood clustering. We found a more than twofold increased risk of both localized and advanced prostate cancer with increasing levels of nSES, and decreased risk of advanced prostate cancer with increasing levels of education. For localized disease, the nSES association was largely explained by known prostate cancer risk factors and specific neighborhood environment factors; population density, crowding, and residential mobility. For advanced disease, associations with education and nSES were not fully explained by any available individual- or neighborhood-level factors. These results demonstrate the importance of specific neighborhood social and built environment factors in understanding risk of localized prostate cancer. Further research is needed to understand the factors underpinning the associations between individual- and neighborhood-level SES and risk of advanced prostate cancer.

Association of Anthropometric Measures with Prostate Cancer among African American Men in the NCI-Maryland Prostate Cancer Case-Control Study.

Background: Obesity is a cancer risk factor. Although it does not increase the risk of localized prostate cancer, it raises the risk of the aggressive disease in men of European ancestry. Few studies investigated obesity as a prostate cancer risk factor in men of African ancestry. Findings from those studies were heterogeneous, but some reported an association of excess body fatness with aggressive disease.Methods: We examined the relationship of body mass index (BMI), waist circumference, and waist-hip ratio with prostate cancer in African American (AA) and European American (EA) men in the NCI-Maryland Prostate Cancer Case-Control Study consisting of 798 men with incident prostate cancer (402 AA and 496 EA) and 1,008 population-based controls (474 AA and 534 EA). BMI was self-reported. Waist circumference and waist-hip ratio were calculated from measurements at enrollment.Results: A high BMI either at enrollment or years prior to it was associated with a decreased risk of prostate cancer in AA men. In contrast, an elevated BMI tended to increase the disease risk in EA men. Waist circumference was inversely associated with prostate cancer in both AA and EA men, whereas a high waist-hip ratio did not associate with prostate cancer in AA men but tended to be associated with advanced/aggressive disease in EA men.Conclusions: Our findings reveal an obesity paradox among AA men in this study population, where a high BMI and waist circumference associated with a decreased disease risk.Impact: Our observations expand the knowledge of how obesity may affect prostate cancer risks in AAs. Cancer Epidemiol Biomarkers Prev; 27(8); 936-44. ©2018 AACR.

Exercise training as a novel primary treatment for localised prostate cancer: a multi-site randomised controlled phase II study

Alternative management strategies for localised prostate cancer are required to reduce morbidity and overtreatment. The aim of this study was to evaluate the feasibility, safety and acceptability of exercise training (ET) with behavioural support as a primary therapy for low/intermediate risk localised prostate cancer. Men with low/intermediate-risk prostate cancer were randomised to 12 months of ET or usual care with physical activity advice (UCwA) in a multi-site open label RCT. Feasibility included acceptability, recruitment, retention, adherence, adverse events and disease progression. Secondary outcomes included quality of life and cardiovascular health indices. Of the 50 men randomised to ET (n = 25) or UCwA (n = 25), 92% (n = 46) completed 12 month assessments. Three men progressed to invasive therapy (two in UCwA). In the ET group, men completed mean: 140 mins per week for 12 months (95% CI 129,152 mins) (94% of target dose) at 75% Hrmax. Men in the ET group demonstrated improved body mass (mean reduction: 2.0 kg; 95% CI −2.9,−1.1), reduced systolic (mean: 13 mmHg; 95%CI 7,19) and diastolic blood pressure (mean:8 mmHg; 95% CI 5,12) and improved quality of life (EQ.5D mean:13 points; 95% CI 7,18). There were no serious adverse events. ET in men with low/intermediate risk prostate cancer is feasible and acceptable with a low progression rate to radical treatment. Early signals on clinically relevant markers were found which warrant further investigation.

Dissecting the heterogeneity of localized prostate cancer risk groups through integration of percent of positive cores.

To develop a modified risk stratification scheme for localized prostate cancer incorporating percent of positive cores (PPC). SEER database was accessed for eligible patients. Assessment of the prognostic value of PPC was conducted in a multivariate Cox regression model. A modified risk stratification scheme was proposed. In a multivariate model, higher PPC was associated with worse cancer-specific survival (p < 0.0001). A modified risk-stratification scheme was proposed incorporating PPC. Concordance index was evaluated and the results were: D'Amico model: 0.782 (SE: 0.014; 95%CI: 0.755-0.810); modified model: 0.809 (SE: <0.001; 95%CI: 0.781-0.837). Integration of PPC into the risk stratification model for localized prostate cancer improves its performance.

Extensión de la indicación de terapia fotodinámica dirigida vascular con padeliporfina (WST11): resultados de un estudio multicéntrico latinoamericano del cáncer de próstata

ObjectivesTo explore the proportion of patients with higher risk localized prostate cancer (PCa) that would become safely biopsy negative 12 months after non-thermal focal therapy with padeliporfin vascular-targeted photodynamic therapy (VTP). MethodsMulticenter study in a scenario of prostate-specific antigen (PSA) ≤20ng/ml and variable PCa target volumes Gleason pattern 3 or low-volume secondary Gleason pattern 4, all patients received VTP, consisting of intravenous 4mg/kg padeliporfin activated by light-diffusing fibers in the prostate. The prostate was biopsied at baseline, months 6 and 12, PSA, patient-reported functional outcomes and quality of life (QoL) questionnaires were recorded at baseline, months 3, 6, and 12 and adverse events (AE) throughout the study. ResultsIn the intention-to-treat population (n=81), the proportion of patients with negative biopsies at month 12 was 74% (60/81 patients; 95% CI: 63.1%,83.2%). In the per-protocol population, the proportion was 79% (58/73 patients; 95% CI: 68.4%,88.0%). Questionnaire results indicated a slight improvement in urinary function and limited deterioration in sexual function. No difference in QoL was observed over time. A total of 42/81 (52%) patients reported mild or moderate and 4 of 81 (4.9%) experienced serious AE, all resolved without sequelae. No phototoxicity, cardiovascular event, fistula or prolonged urinary incontinence, secondary cancer or death was reported. ConclusionsResults support the efficacy, safety, and QoL associated with padeliporfin focal treatment for low/intermediate risk localized PCa.

Comparison of intrafascial and non-intrafascial radical prostatectomy for low risk localized prostate cancer

In this meta-analysis study, we compared the oncological and functional outcomes of intrafascial radical prostatectomy (IFRP) with non-intrafascial radical prostatectomy (NIFRP) in the treatment of patients with low risk localized prostate cancer (PCa). Relevant articles were identified by searching PubMed, EMBASE, Cochrane Library, Ovid, and the ISI Web of Knowledge databases. A total of 2096 patients were included from 7 eligible studies. Results of the pooled data showed that the oncological outcomes including gleason score, positive surgical margin and biochemical free survival rates were similar between the two groups. IFRP was superior to NIFRP with lower postoperative complication rates (RR 0.57, 95% CI 0.38, 0.85, p = 0.006), higher continence rates at 3 months post-operation (RR: 1.14; 95% CI, 1.04, 1.26; p = 0.006), and higher potency rates at 6 months (RR: 1.53; 95% CI, 1.07, 2.18; p = 0.02) and 12 months post-operation (RR: 1.38; 95% CI, 1.11, 1.73; p = 0.005). Additionally, there was a tendency towards higher potency rate in patients ≤65 years old compared with patients >65 years old after IFRP. Overall, these findings suggest that IFRP in young patients with low risk localized PCa had less postoperative complications, shortened time to return to continence and improved potency rate without compromising complete tumor control.

Abstract 1062: The combination of metformin and valproic acid induces synergistic apoptosis of prostate cancer cells via p53 activation and the intrinsic pathway

Abstract The anti-diabetic drug metformin (MET) and the anti-epileptic drug valproic acid (VPA), when used alone, have demonstrated anti-cancer effects in prostate cancer (PCa). We have demonstrated that the combination of MET and VPA (MET+VPA) can induce synergistic apoptosis in the human prostate cancer cell line LNCaP (p53+) but not in PC3 (p53-), and that the response is dependent on functional p53. Here, we aimed to (1) investigate the mechanism of synergistic apoptosis induced by MET+VPA in LNCaP and (2) propose patient subsets for clinical applications of MET+VPA based on the mechanism involved. LNCaP and PC3 cells were treated with vehicle, 2.5 mM MET, 2.5 mM VAL, or 2.5 mM MET+VAL and proteins extracted from cell fractions. Western blots were used to confirm cytoplasmic and mitochondrial fractions by measuring the presence of β-actin, pyruvate dehydrogenase subunit E1-α, and ATP synthase subunit-α protein, as well as the release of cytochrome c from mitochondria to the cytoplasm. The mechanism of apoptosis via p53 activation is proposed based on our findings and current understanding from literature. The release of cytochrome c from the mitochondria to the cytoplasm was significantly increased up to 12-fold (p&amp;lt;0.05) in LNCaP, but not in PC3, in response to MET+VPA compared to vehicle, MET alone, and VPA alone. This finding suggests that both MET and VPA are required to induce an intrinsic apoptosis response in LNCaP via p53. The mechanism proposed is that MET can inhibit the activity of mitochondrial complex 1 which alters the AMP/ATP ratio. This change can activate adenosine monophosphate protein kinase which phosphorylates p53 at Ser15 and leads to p53-dependent cell death. As a non-specific histone deacetylation inhibitor, VPA causes protein acetylation including p53 at lysine residues 373 and 382. By combining metformin and VPA, increased p53 protein activation can occur through phosphorylation of p53 at different sites driving p53-dependent cell apoptosis via the intrinsic pathway, as evidenced by release of cytochrome c into the cytoplasm. Our results suggest that MET+VPA provides a useful treatment for PCa at a clinically localized stage where p53 is present in most patients or advanced stage where p53 has not been mutated. Additionally, MET+VPA is potentially an alternative to androgen deprivation therapy, particularly in tumors with functional p53. A phase I neo-adjuvant clinical trial will start in early 2017 to evaluate the response of high risk localized PCa to MET+VPA (ANZCTR trial ID: ACTRN12616001021460). Citation Format: Linh N.K. Tran, Ganessan Kichenadasse, Katherine L. Morel, Pamela J. Sykes. The combination of metformin and valproic acid induces synergistic apoptosis of prostate cancer cells via p53 activation and the intrinsic pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1062. doi:10.1158/1538-7445.AM2017-1062