Initial Gleason Score Research Articles

The factors impacting on Gleason score upgrading in prostate cancer with initial low Gleason scores

BackgroundThis study aims to investigate the factors contributing to the discrepancy in between biopsy Gleason score (GS) and radical prostatectomy GS in patients diagnosed with prostate cancer. Methods341 patients who underwent radical prostatectomy from 2011/04 to 2020/12 were identified. 102 Patients with initial GS of six after biopsy were enrolled. Preoperative clinical variables and pathological variables were also obtained and assessed. The optimal cut-off points for significant continuous variables were identified by the area under the receiver operating characteristic curve. ResultsUpgrading was observed in 63 patients and non-upgrading in 39 patients. In the multiple variables assessed, smaller prostate volume (PV) (p value = 0.0007), prostate specific antigen density (PSAD) (p value = 0.0055), positive surgical margins (p value = 0.0062) and pathological perineural invasion (p value = 0.0038) were significant predictors of GS upgrading. To further explore preclinical variables, a cut-off value for PV (≤ 38 ml, p value = 0.0017) and PSAD (≥ 0.26 ng/ml2, p value = 0.0013) were identified to be associated with GS upgrading. ConclusionsSmaller PV and elevated PSAD are associated with increased risk of GS upgrading, whereas lead-time bias is not. A cut-off value of PV < 38 ml and PSAD > 0.26 ng/ml2 were further identified to be associated with pathological GS upgrading.

The utility of [18F]Fluciclovine PET/CT in Evaluating Nonmetastatic Castrate-Resistant Prostate Cancer Patients (nmCRPCp): diagnostic performance and impact on management.

To evaluate the role of [18F]Fluciclovine PET/CT scan in restaging nmCRPCp and its impact on management. This retrospective study included all patients with nonmetastatic castrate-resistant prostate cancer, who underwent [18F]Fluciclovine PET/CT scans for restaging who had concern for disease progression. Two radiologists independently reviewed the PET/CT studies, assigned an overall impression, and reported the site and number of radiotracer activities in consensus and impact on management was recorded. Available tissue diagnosis and/or six-month clinical and imaging follow-up were used as reference standards. Thirty-five patients were included in this study. At least one lesion was detected in 73% (26/35) of the scans. Management changed in 71% (25/35) of patients, (22 positives and three negative scans). 26.9% (7/26) of patients were found to have an oligometastatic disease. Based on the reference standards, the diagnostic performance of [18F]Fluciclovine PET/CT in detecting recurrence in nmCRCP has 86%, sensitivity, 83% specificity, 96.1% PPV, and 55.5% NPV. There was no relationship between the Gleason score and a positive PET/CT scan in our patient population. Detecting the source of recurrence is challenging in nmCRCP patients when conventional imaging fails. Given the high PPV, sensitivity, and specificity, [18F]Fluciclovine PET/CT can be used instead of conventional imaging as a first-line choice due to its superiority over bone scan and added value of detecting soft tissue metastasis regardless of the initial Gleason score. The study highlights the added value of [18F]Fluciclovine PET/CT in detecting soft tissue metastasis regardless of the initial Gleason score, which is not possible with conventional imaging such as bone scans.The study highlights the potential role of [18F]Fluciclovine PET/CT guiding management change for nonmetastatic castrate-resistant prostate cancer patients, particularly those with oligometastatic disease.

Time trends of overall survival and other outcomes in patients with mHSPC: An observational study of U.S. EHR data (TIMES).

e17051 Background: Patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC) are responsive to androgen deprivation therapy (ADT), but within 1–3 years most will develop metastatic castration-resistant prostate cancer (mCRPC). The CHAARTED trial showed a clear benefit of adding docetaxel (DTX) to ADT, prolonging median overall survival (OS) by 10.4 months (mo). ARASEC is a single-arm US study evaluating darolutamide + ADT in pts with mHSPC. Participants will be matched for comparison using patient-level data to the ADT alone arm of CHAARTED. The TIMES study evaluated a potential time bias in treatment patterns and clinical outcomes in pts with mHSPC before and after the OS analysis of CHAARTED was reported. Methods: This retrospective study used Flatiron Metastatic PC Core Registry data from January 1, 2013, to June 30, 2020, and the sample was divided into two cohorts: before and after June 30, 2016 (cohort 1: pre-CHAARTED; cohort 2: post-CHAARTED). Differences in OS and time to mCRPC were assessed using Cox proportional hazard models, controlling for baseline characteristics, including age, initial mHSPC treatment, Gleason score, and time from PC diagnosis to mHSPC. The test for equivalence used hazard ratio (HR) limits of 0.80 to 1.25 at a 2-sided 0.05 level. Results: Data from 9256 pts with mHSPC (4503 in cohort 1; 4753 in cohort 2) were analyzed; median age was 73 years for both cohorts. M1 status at initial diagnosis was 55% in cohort 1 and 60% in cohort 2. All other clinical characteristics and laboratory values were similar. Initial mHSPC treatment with DTX was 10.5% and 13.9%, whereas treatment with novel anti-hormonal agents (NAH) was 1.6% and 18.3% in cohorts 1 and 2, respectively. The percentage of pts who started with first-generation androgen receptor inhibitors decreased from 29.3% in cohort 1 to 19.6% in cohort 2, whereas the percentage of pts receiving ADT alone and/or supportive care remained stable (25.7% and 26.5%, respectively). In cohorts 1 and 2, treatment records during the mHSPC period could not be retrieved for 32.9% and 21.7% of pts, respectively. Median OS was 5.4 months longer for cohort 1 (43.7 mo) vs cohort 2 (38.3 mo). In multivariate analyses, cohort 2 had poorer survival, with an HR slightly outside the predefined limits for equivalence (HR 1.19; 95% CI 1.09, 1.29; P &lt; 0.0001). The HR for time to mCRPC fell within the predefined limits (HR 1.16; 95% CI 1.09, 1.23). Conclusions: Changes in treatment patterns were observed following CHAARTED. Although DTX and NAH have demonstrated prolonged survival, their use increased only from 12% to 32%, comparing the cohorts before and after 2016, which is not in line with guideline recommendations. Clinical outcomes, despite the influence of multiple factors, have changed minimally during the past 5 years, suggesting that the risk of historical time bias associated with using the CHAARTED ADT alone arm as a comparator for ARASEC is low.

Bone Uptake in Prostate Cancer Patients: Diagnostic Performances of PSMA-RADS v1.0, Clinical, Biological, and 68 Ga-PSMA-11 PET Features to Predict Metastasis After Biochemical Recurrence.

68 Gallium-labeled prostate-specific membrane antigen-11 (PSMA) PET/CT is the new reference to identify relapse during biochemical recurrence of prostate cancer (PCa). However, this method lacks specificity for bone foci. This study aimed to report the prevalence of PCa bone metastases and to assess the diagnostic performances of PSMA reporting and data systems (RADS), clinical, biological, and imaging features for identification. A multicentric retrospective cohort of consecutive patients with biochemical recurrence after local treatment was analyzed. Clinical and biological features at initial staging and during recurrence were retrieved from medical reports. The metastatic status of each bone uptake on PSMA PET/CT was determined according to histopathology, comparisons with concomitant and previous conventional imaging, prostate-specific antigen kinetic, and follow-up. Two nuclear medicine physicians assessed PSMA-RADS, anatomic location, radiological patterns, SUV max , and the presence of other molecular lesions. Univariate and multivariate analyses were conducted to identify independent predictors of PCa metastases. In the eligible population, 98/298 patients (32.9%) showed bone uptake on PSMA PET/CT. In patients with a final diagnosis, 28/81 lesions (34.6%) were metastases. PSMA-RADS-4 or 5 showed sensitivity of 79%, specificity of 94%, and accuracy of 89%. PSMA-RADS had a significantly higher area under the receiver operating characteristic curve than the initial reading in clinical practice (0.91 vs 0.83, P = 0.0074). Initial Gleason score ≥8, age ≤71 years at recurrence, and SUV max >6.21 were independent predictors of PCa metastases in multivariate logistic regression ( P = 0.0314, 0.0179, and 0.0003, respectively). Most bone uptakes at PSMA PET/CT were benign lesions. PSMA-RADS, patients and tumor characteristics, and SUV max could help identify PCa bone metastases.

Grade migration and important prognostic factors in a pathology specimen for radical radiotherapy in prostate cancer patients.

The study aimed to evaluate grade migration and prognosis depending on pathologic features in patients with prostate cancer treated with radical external beam radiotherapy. The study included 139 patients with an initial Gleason score of 7 (3+4 or 4+3) i.e., Grade Group 2-3 (GG2-GG3) treated between 2008 and 2013. The clinical outcome was assessed with respect to biochemical control (BC) and biochemical disease-free survival (bDFS). After re-evaluation, the majority of patients (96 patients - 69%) were up-graded from GG2-3. Finally, there were 4 patients (3%) with grade GG1, 12 patients (9%) - GG2, 27 patients (19%) - GG3, 51 patients (37%) - GG4 and 45 patients (32%) - GG5. In 42 patients (30%) a cribriform pattern was observed. Among the analyzed factors only the GGs were important for BC (p = 0.011) and the cribriform pattern was of borderline significance (p = 0.06). The 5-year biochemical control was 100% in GG1-3 and 84% in GG4-5. The 5-year biochemical control was 81% and 93%, if cribriform or no cribriform pattern was detected, respectively. In conclusion, re-evaluation and verification of pathology specimens in accordance with contemporary rules upgraded the Gleason score in the majority of patients. The aggressive behavior of prostate cancer starts to occur from GG 4. Cribriform pattern almost tripled the biochemical failure rate.

Initial Institutional Experience with 18F-Fluciclovine PET-CT in Biochemical Recurrence of Prostate Cancer.

18F-fluciclovine (fluciclovine) is an amino acid analog approved by the Food and Drug Administration for use as a radiotracer in positron emission tomography (PET) in men with biochemical recurrence of suspected prostate cancer. The purpose of this study was to investigate the initial institutional experience with 18F-fluciclovine in the evaluation of prostate cancer with biochemical recurrence. This study was a retrospective review of 135 patients who underwent 18F-fluciclovine PET-computed tomography (PET-CT) at a single institution from August 2018 through January 2020. Prognostic information, including prostate-specific level antigen (PSA) at the time of diagnosis, initial risk, initial Gleason score, and initial stage, was reviewed as well as the PSA level at the time of the scan. The images were reviewed by two radiologists with fellowship training in nuclear medicine and additional training to interpret the fluciclovine studies. A minority of studies were reviewed by a third fellowship-trained radiologist under the guidance of the two nuclear medicine-trained radiologists. In cases with abnormal radiopharmaceutical uptake in lymph nodes, the short-axis dimension of the lymph node or largest lymph node with abnormal uptake was noted. If CT or bone scan was performed within 4 months of the 18F-fluciclovine PET-CT, findings on the alternate imaging were compared with the results of the 18F-fluciclovine PET-CT. Our institutional positivity rate was 75.6%, with 64 (67.4%) patients with metastatic disease and 71 (52.6%) patients with local recurrence detected by fluciclovine. As expected, the rate of positive examinations increased with increasing PSA values measured at the time of imaging (P < 0.001). Of the 54 patients with nodal disease, 35 had nonpathologically enlarged lymph nodes measuring <1 cm in maximum short-axis dimension. In more than half of the patients in this study, with conventional imaging, fluciclovine either discovered otherwise undetectable metastatic disease or suggested the presence of local recurrence. Our single-institution experience with 18F-fluciclovine PET-CT has the largest number of patients to date in the literature and demonstrates the ability of fluciclovine to help guide clinical management in the detection of early recurrent disease.

Detection of Failure Patterns Using Advanced Imaging in Patients With Biochemical Recurrence Following Low Dose Rate Brachytherapy for Prostate Cancer

Low dose rate (LDR) brachytherapy alone or with external beam radiation (EBRT) results in excellent rates of biochemical control in patients (pts) with prostate cancer (PCa). Understanding failure patterns in pts with biochemical recurrence (BCR) may inform implant technique or pt selection. The primary objective of this study was to describe locations of recurrence on multiparametric MRI (mpMRI) and prostate specific membrane antigen (PSMA) imaging in pts with BCR after LDR brachytherapy.Pts with BCR after definitive LDR (± EBRT, ± androgen deprivation therapy (ADT)) referred for IRB approved imaging protocols were included. All pts underwent 3T mpMRI (T2 weighted, dynamic contrast-enhanced, and diffusion-weighted imaging) prospectively reviewed by prostate-dedicated radiologists. A subset of pts underwent PSMA-PET/CT imaging. Pathologic confirmation was obtained unless contraindicated. Prostate lesions were categorized as left (L)/right (R)/midline (ML); transitional zone (TZ)/peripheral zone (PZ); apical/mid/base; and anterior/posterior/central. Locations of recurrence (prostate, seminal vesicles (SV), lymph nodes (LN) and distant metastases (DM)) were recorded and reported descriptively.Between Jan 2011 and Feb 2021, 57 pts with BCR after LDR underwent prostate mpMRI. Treatment was LDR (n = 39) or EBRT + LDR (n = 18), ± ADT (n = 12). At time of LDR, initial Gleason score was ≤6 (n = 29), 7 (n = 19), 8-9 (n = 8), unknown (n = 1) and median PSA was 6 ng/mL (3.4-49). Of dosimetry available (n = 27), 2 had D90 < 90%. Median time from LDR to mpMRI was 6.7 yrs (0.8-18.3). At time of mpMRI, median pt age was 68 yrs (51-85), median PSA was 5.64 ng/mL (0.17-37.47). Lesions (n = 67) in the prostate/SV were detected in 45/57 pts on mpMRI, with a median lesion size of 1.2 cm (0.3-3.6). SV involvement was present in 20/45 patients with mpMRI detected lesions. Locations of mpMRI prostate lesions were L (n = 19) vs R (n = 16) vs ML (n = 15); TZ (n = 22) vs PZ (n = 14); apical (n = 17) vs mid (n = 25) vs base (n = 23); and anterior (n = 13) vs posterior (n = 0) vs central (n = 8). In pts with PSMA (n = 32), 31 had uptake in the prostate (n = 16, 14 detected on mpMRI) and SV (n = 12, 10 detected on mpMRI). One pt had uptake in the prostate+SV detected only on PSMA. Extraprostatic uptake on PSMA included LN (n = 15), DM (n = 5) and penile bulb (n = 1). Of 37 pts who had prostate/SV biopsy, tumor recurrence was confirmed in 31 (prostate (n = 25) and SV (n = 12)). Three of 6 pts with negative biopsy had no lesion on mpMRI. SV recurrence (imaging ± biopsy) occurred in 18/39 pts with LDR alone and in 5/18 with LDR + EBRT.In this cohort of pts with BCR following LDR, the predominant locations of local recurrence were in the anterior/central TZ and SV. PSMA corroborated the majority of mpMRI findings and often demonstrated LN and DM. These findings may inform LDR technique and impact patient selection or pre-treatment imaging evaluation; and should be confirmed in larger subsets and correlated with post-implant dosimetry.

Could an Academic Review of Pathology Lead to Changes in Patient Care in Men With Prostate Cancer?

Approximately 200,000 men per year are diagnosed with prostate cancer, a disease that causes over 30,000 deaths per year, making it the second leading cause of cancer mortality among men. There are multiple treatment options for patients with low, intermediate and high-risk disease. However, a successful treatment regimen is dependent on accurate pathologic evaluation of the Gleason Score (GS) in addition to imaging and physical exam findings. Here, we report our experience with changes in pathologic diagnosis seen in a multi-disciplinary community-based practice.This is a retrospective review of patients who had a pathologic diagnosis of prostate adenocarcinoma seen at our institution from Jan 2017 to March 2019. Patients underwent a re-review of their pathology at our institution with pathologists using established institutional protocols for pathologic review. All patients were seen in an academic multidisciplinary setting. Pathology was re-reviewed at our institution at or before the time of consult. Additionally, patient cases were discussed in a multi-disciplinary tumor board with Urology, Medical Oncology and Radiation Oncology. Medical records were reviewed and demographic data, initial and final pathologic diagnosis and any changes in treatment plans were recorded. Descriptive statistics were used in this analysis.A total of 300 patients (pts) were treated in either the definitive or adjuvant/salvage setting for their prostate cancer. 23 pts had an initial GS 6 disease, 70 pts had GS 3+4 disease, 68 had GS 4+3 disease, 58 had GS 4+4, 72 had GS4+5 or 5+4 and 9 patients had Gleason 5+5 disease. 270 (90%) men underwent radiation therapy treatment for definitive prostate cancer and 30 (10%) men underwent radiation therapy in the adjuvant and/or salvage setting. 101 (34%) men had a change in pathologic diagnosis after re-review with our institution's pathologists, specifically 44 (44%) had a decrease or downgrade in Gleason score and 57 (56%) had an increase in Gleason score. 199 (66%) pts had no change in pathology on re-review. Additionally, 5 men had a change in pathology in the post op group versus 96 men had a change in pathology in the intact group (P = 0.150). Interestingly, there were no changes in treatment plan in the post-op group versus 14 men had a change in treatment plan in the intact group. Similarly, there were 34 patients in the intact group who had changes in staging risk stratification after re-review and only 1 patient in the post-op group with changes in staging risk stratification.Overall, we found that 34% patients had a change in pathologic diagnosis following re-review at a multi-disciplinary institution. These initial results suggest the importance of a multi-disciplinary, academic approach to not only the treatment but also diagnosis and staging for men with prostate cancer.

Salvage Low Dose Rate Prostate Brachytherapy: Clinical Outcomes of a Phase II Trial for Local Recurrence after External Beam Radiotherapy (NRG/RTOG -0526)

Prior studies of low dose rate (LDR) prostate brachytherapy (BT) for salvage of local recurrence (LR) of prostate cancer (PCa) after external beam radiotherapy (EBRT) are limited by retrospective reporting. We previously reported adverse events (AEs) of a prospective Phase II trial (NCT00450411) and now report efficacy outcomes with a minimum potential follow up of 5 yrs. Eligible patients had low or intermediate risk PCa prior to EBRT and biopsy-proven LR > 30 mos after EBRT, with PSA < 10 ng/mL and no regional or distant disease. Prescribed minimum target dose was 140 Gy with I-125, or 120 Gy with Pd-103. The primary endpoint, late GI/GU AEs occurring 9-24 mos after BT (CTCAE V3.0 > Grade 3; attributed to BT) was 14%. All eligible patients were followed for a minimum of 5 yrs after salvage BT and analyzed for secondary clinical outcomes. Disease-free (DFS), disease-specific (DSS), and overall (OS)survivals were estimated using the Kaplan-Meier method and 95% confidence intervals computed using Cox proportional hazards models. Local tumor progression (LR), distant failure (DF), and biochemical failure (BF) were estimated using nonparametric estimation of cumulative incidence accounting for competing risk events. Time to LR, DF and BF were modeled by cause-specific Cox proportional hazards regression and adjusted for clinical and treatment factors. From May 2007 – January 2014, 20 centers registered 100 patients with 92 analyzable. Median follow up is 6.9 yrs (range: 0.3-11.2); median age 70 (IQR: 66-74). Initial Gleason score was 7 in 48% and PSA >10 ng/mL in 16%. Median prior EBRT dose was 74 Gy (IQR: 70-76). Androgen deprivation was combined with salvage BT in 16%. Median interval from prior EBRT was 85 mos (IQR: 60-119). 10-yr OS is 70% (95% CI: 58 -83). Nineteen patients died (5 PCa, 10 other, 4 unknown). 4 had LR (one biopsy-confirmed). 10-yr LF rate is 5% (95% CI:1-11). 14 patients had DF (10-yr rate 19% (95% CI:10-29)). The 10-yr freedom from BF rate is 54% (95% CI:43-66). DFS is 61% at 5 yrs (includes death from any cause) but falls to 33% at 10 yrs. None of the baseline characteristics, including % of prostate covered by 100% of the prescription dose and interval from EBRT to BT were significantly associated with OS, DFS, local, distant, or biochemical failure. This is the first prospective multicenter trial to report outcomes of salvage LDR BT for LR after EBRT. We previously reported late grade 3 GU/GI adverse events occurring in14%. We now report 5-yr freedom from biochemical failure at 68%, comparable to other salvage modalities. Although further local LF is rare (5%), there is a continued toll of PCa recurrence such that freedom from biochemical failure at 10 yrs is 54%.

Is There Any Role for 18F-Fluciclovine PET/CT in the Presence of Undetectable PSA in Prostate Cancer Patients After Definitive Treatment?

The aim of this study was to investigate the role of F-fluciclovine PET/CT in the evaluation of prostate cancer (PC) patients after definitive treatment in the presence of undetectable prostate-specific antigen (PSA). This retrospective study was conducted in PC patients who had undetectable PSA level and underwent fluciclovine PET/CT within a 2-week interval of PSA examination and without interval treatment or other cancer. Patient and tumor characteristics at initial diagnosis, treatment regimens, and findings on fluciclovine PET/CT were collected. Comparisons between groups of positive and negative fluciclovine PET/CT were done by using descriptive statistics. A total of 34 fluciclovine PET/CTs from 34 patients met the inclusion criteria. There were 4 positive (11.8%) and 30 negative fluciclovine PET/CTs (88.2%). All of the patients with positive results had an initial Gleason score of 7 or higher and locally advanced tumor (T3-T4). More common features at the time of diagnosis among positive study patients as compared with negative ones were atypical histologic variants (25% vs 0%) and very high-risk PC (50% vs 30%). Most of the patients with positive study received second-line hormonal therapy (HT) (50%), whereas patients with negative results received first-line HT (53.3%). Chemotherapy naivety was less common among positive patients (75% vs 96.7%). Sites of involvement on positive fluciclovine PET/CTs were pelvic lymph nodes (2/4, 50%), lung and mediastinal lymph node (1/4, 25%), and prostatectomy bed (1/4, 25%). In the presence of undetectable PSA in PC patients after definitive treatment, fluciclovine PET/CT would benefit most to patients with Gleason score of 7 or higher, high disease burden (T3-T4), and atypical histologic variants at the time of diagnosis, and the ones who have history of second-line HT and/or chemotherapy.

Association between low prostate-specific antigen levels and greater disease progression in high-grade locally-advanced prostate cancer

In advanced or high-grade prostate cancer (PCa), prostate-specific antigen (PSA) is usually elevated, however, some patients may present with low initial PSA (iPSA) levels. The objective of this study was to evaluate whether different iPSA levels were associated with dissimilar clinical outcomes among men with high-grade PCa and advanced disease after robot-assisted laparoscopic radical prostatectomy (RaLRP). This study enrolled 69 PCa patients with initial Gleason score ≥8 and pathologic T-stage ≥3a from April 2012 to December 2018. Patients were stratified into 3 groups based on iPSA levels at diagnosis: <5.0, 5.0-9.9, and ≥10.0. The patients' related parameters were compared among these groups. The median follow-up period was 33.1 months (IQR: 12.1-48.1). There was no difference in biochemical recurrence (BCR) between the 3 groups (Log-rank test, p=0.484). We found a higher risk of biochemical recurrence in patients with positive surgical margins (HR: 5.04, 95% CI: 1.64-15.50, p=0.005). In addition, patients with low iPSA levels (<5.0ng/mL) had poor radiographic progression-free survival (Log-rank test, p=0.001) and a higher risk of disease progression (HR: 12.2, 95% CI: 1.18-1260.99, p=0.036) compared with patients with higher iPSA levels (≥10ng/mL). In patients with high-grade locally-advanced PCa, a low iPSA level was associated with a higher risk of disease progression, but not with biochemical recurrence. In this unique population, serum PSA may not be a reliable marker to detect disease progression. Monitoring of these patients may warrant other biomarkers or imaging.

Pattern of prescribing after disease progression following upfront docetaxel in metastatic hormone-naïve prostate cancer within the UK: Results from a national study.

e19190 Background: Upfront docetaxel is now standard of care for men with newly diagnosed metastatic hormone naïve prostate cancer .After disease progression following upfront docetaxel, various treatment agents including further lines of chemo or novel hormonal agents are used but there have been no convincing evidence or consensus opinion about optimal sequencing. Methods: We have conducted a national study in the UK by approaching oncologists who treat prostate cancer with systemic therapies. The oncologists were requested to complete a web based survey about their treatment decisions . Aim were to gain an insight about current practice following docetaxel in the UK and to identify the various disease and patients related factors which could influence the decision-making process. Results: 114 oncologists were invited and 59 have responded, 80% clinical oncologist and 20% medical oncologists respectively. At the point of castrate-resistant disease progression, following docetaxel, abiraterone was most commonly used agents (63%), followed by Enzalutamide (29%), cabazitaxel (6%) and docetaxel re-challenge respectively. Time difference between finishing docetaxel and disease progression was considered the most important deciding factor to choose next agents. Other important factors as per responders were volume of the disease, patients current symptoms, co morbidities and site of metastases . Most oncologists felt initial PSA and Gleason scores were two least important deciding factors. Patients with low volume disease, 92 % oncologist preferred abiraterone or enzalutamide as opposed to chemotherapy. When disease progressed within 6 months of completion of docetaxel, only one fifth of responder would use further chemo in next line .After novel hormone agents, cabazitaxel was the most commonly prescribed agents. 81% of clinicians would consider re-challenging with Docetaxel at some point of treatment sequencing; of these the majority would only consider this after a minimal interval of 12-18 months following upfront treatment. Conclusions: Our study has demonstrated a wide variation of practice in the UK. It has reflected that the decision is complex and there is clear need for further evidence or guideline for sequencing.

Clinical and Histopathological Characteristics of Prostate Cancer Patients Taken to Palliative Transurethral Prostate Resection.

IntroductionIn prostate cancer (PCa) patients who have been treated with radiotherapy and/or androgen deprivation therapy (ADT), palliative transurethral resection of the prostate (TURP) is a management option in the presence of lower urinary tract symptoms (LUTS). The present work seeks to describe the clinical and histopathological characteristics of patients with PCa taken to palliative TURP.MethodsAn observational, descriptive and retrospective study of patients with PCa who underwent palliative TURP for the relief of obstructive urinary symptoms at an oncology reference center between January 2006 and June 2014 was performed. Among the included patients were those with localized PCa treated with radiotherapy and those with advanced PCa with or without metastasis who had previously received ADT.ResultsSixty-six patients with a diagnosis of PCa taken to palliative RTUP were identified. Fifty patients (78.4%) were received some type of ADT, seven patients (10.7%) received curative radiotherapy along with adjuvant ADT, five patients (7.8%) were previously treated with only radiotherapy, and two patients (3.1 %) had received no prior management and thus were taken to bilateral orchiectomy along with palliative TURP in a single surgical act. With regard to the pathology reports, tumor tissue was found in 50 patients (76%), and no tumor was observed in the remaining 16 patients (24%). In one case (1.5%), the Gleason score (GS) could not be determined due to the effects of orchiectomy. Under-staging in the grade group was evidenced in 23 patients (46.9%), over-staging in three patients (6.3%), and no difference in 23 patients (46.9%), when compared to the initial GS at biopsy. The mortality rate and the incidence of TURP syndrome were low (3.1% and 1.5%, respectively). A 46% reduction in the mean serum prostate-specific antigen (PSA) value was documented when the preoperative and postoperative values were compared.ConclusionA decrease in the serum PSA levels was observed after palliative TURP, and despite having received ADT, it was possible to determine tumor pathology in the resected tissue, being able to identify a greater grade group compared the GS at the time of diagnosis. The palliative TURP proved to be a safe procedure to relieve LUTS in patients with advanced PCa, with a low morbidity and mortality rate.

PD25-10 ESTIMATION OF THE RISK OF MISSING ADVERSE PATHOLOGICAL PROSTATE CANCER FEATURES AFTER SALVAGE RADICAL PROSTATECTOMY IN PATIENTS ELIGIBLE FOR FOCAL SALVAGE THERAPIES

INTRODUCTION AND OBJECTIVES:Focal salvage therapies (FST) for locally recurrence prostate cancer (PCa) after primary radiotherapy (RT) can reduce the risk of adverse events associated with salvage radical prostatectomy (sRP) while maintaining cancer control, in selected patients. However, the risk of missing adverse PCa features undergoing FST instead of sRP has never been investigated. We aimed to assess the rates and predictors of adverse PCa features in patients eligible for FST who ultimately underwent sRP.METHODS:We reviewed 120 patients with locally recurrent PCa after RT who underwent sRP and extended pelvic lymph node dissection (2000-2016). Metastatic disease was excluded by choline PET and bone scan. Pre RT PSA, clinical stage (cT), biopsy Gleason score (GS) prior to RT and prior to sRP, PSA nadir, PSA prior to surgery, and pathohistology of sRP specimens were analysed. Eligibility criteria for FST were based on EAU Guidelines: cT1-cT2 PCa, initial GS ≤7 and pre-salvage PSA <10 ng/mL. Adverse fe...

Experience with using fosfestrol for treating metastatic castrate-resistant prostate cancer in resource-limited setting

Abstract Background: Fosfestrol is a low-cost estrogen analog that is useful in the management of metastatic prostate cancer in resource-challenged settings. It acts by altering the pituitary axis, adrenal secretion, and 5-alpha reductase activity. Patients and Methods: The outcomes of metastatic castration-resistant prostate cancer patients treated with fosfestrol in our center between June 2012 and December 2015 were analyzed retrospectively. Fosfestrol was given orally at a dose of 120 mg thrice daily. Event was defined as the discontinuation of fosfestrol due to tumor progression or drug toxicity or death due to any cause. The event-free survival (EFS) and overall survival (OS) were calculated by the Kaplan–Meier method. Results: The analysis included 47 patients with a median age of 65 years. Initial Gleason score was available for 41 of 47 patients, of which 17% (7), 39% (16), and 44% (18) were low risk, intermediate risk, and high risk, respectively. The most common site of metastasis was bone (98%). Of 47 patients, 32 (68%) received fosfestrol as the second line of treatment after progression on complete androgen blockade, 14/47 (30%) received it as the third line, and 1/47 received it as the fourth line of treatment. The median prostate-specific antigen (PSA) value at the start of fosfestrol and the nadir PSA value were 43.7 ng/ml and 13.1 ng/ml, respectively. Ninety-one percent (n = 43) of patients had not been previously treated with chemotherapy (docetaxel). Response of PSA of &gt;50% was observed in 55% (n = 26) of patients. The median EFS and median OS after the start of fosfestrol were 6.8 and 14.7 months, respectively, with a median follow-up of 10.9 months. Only two patients developed Grade 3 toxicity, both of whom had diarrhea. Conclusions: In resource-challenged settings, oral fosfestrol is an effective, cheap, and safe option for the management of metastatic prostate cancer progressing after first-line complete androgen blockade.

A Prospective Phase 2 Trial of Transperineal Ultrasound-Guided Brachytherapy for Locally Recurrent Prostate Cancer After External Beam Radiation Therapy (NRG Oncology/RTOG-0526)

Only retrospective data are available for low-dose-rate (LDR) salvage prostate brachytherapy for local recurrence after external beam radiation therapy (EBRT). The primary objective of this prospective phase 2 trial (NCT00450411) was to evaluate late gastrointestinal and genitourinary adverse events (AEs) after salvage LDR brachytherapy. Eligible patients had low- or intermediate-risk prostate cancerbefore EBRT and biopsy-proven recurrence >30months after EBRT, with prostate-specific antigen levels <10ng/mL and no regional/distant disease. The primary endpoint was grade 3 or higher late treatment-related gastrointestinal or genitourinary AEs occurring 9 to 24months after brachytherapy. These AEs were projected to be ≤10%, with ≥20% considered unacceptable. All events were graded with National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Multivariate analyses investigated associations of pretreatment or treatment variables with AEs. One hundred patients from 20 centers were registered from May 2007 to January 2014. The 92 analyzable patients had a median follow-up of 54months (range, 4-97) and a median age of 70years (interquartile range [IQR], 65-74). The initial Gleason score was 7 in 48% of patients. The median dose of EBRT was 74Gy (IQR, 70-76) at a median interval of 85months previously (IQR, 60-119). Only 16% had androgen deprivation at study entry. Twelve patients (14%) had late grade 3 gastrointestinal/genitourinary AEs, with no treatment-related grade 4 or 5 AEs. No pretreatment variable predicted late AEs, including prior EBRT dose and elapsed interval. Higher V100 (percentage of prostate enclosed by prescription isodose) predicted both occurrence of late AEs (odds ratio, 1.24; 95% confidence interval, 1.02-1.52; P=.03) and earlier time to first occurrence (hazard ratio, 1.18; 95% CI, 1.03-1.34; P=.02). This prospective multicenter trial reports outcomes of salvage LDR brachytherapy for post-EBRT recurrence. The rate of late grade 3 AEs did not exceed the unacceptable threshold. The only factor predictive of late AEs was implant dosimetry reflected by V100. Efficacy outcomes will be reported at a minimum of 5-year follow-up.

Neuroendocrine prostate cancer

Neuroendocrine prostate cancer (NEPC) mostly occurs as atreatment-emergent adaptive response under the pressure of intensive androgen deprivation treatment (t-NEPC). Approximately 30-40% of patients with metastatic castration-resistant prostate cancer (mCRPC) also have neuroendocrine involvement. In contrast primary small cell prostate cancer is very rare (<1%). A t‑NEPC should be clinically suspected in patients who have particularly aggressive mCRPC but a disproportionately low prostate-specific antigen (PSA) level and elevated neuroendocrine tumor markers, such as chromograninA and neuron-specific enolase. The initial Gleason score was shown to be an independent factor correlated to the risk of development of t‑NEPC. Treatment is oriented to that of small cell lung cancer. In patients with negative PSA levels, chemotherapy with cisplatin and etoposide is the first line treatment, for which response rates in the range of 30-60% with amedian survival time of usually less than 1year can be achieved. In patients with much higher serum PSA levels, chemotherapy with carboplatin plus docetaxel should be considered.

Validation of the WHO 2016 new Gleason score of prostatic carcinoma.

Context:New Gleason Score of Prostate.Aims:The aim of this study is to assign the patients with carcinoma prostate into new prognostic grade groups (PGGs) based on revised Gleason score (GS) and follow-up according to the WHO 2016.Subjects and Methods:All the biopsies/resected specimens of carcinoma prostate from January 2014 to June 2016 were reviewed, and GS was done according to the WHO 2016. Accordingly, cribriform, fused, and glomeruloid glands were assigned GS 4. Thus, two groups were identified with GS 7 (3 + 4 and 4 + 3). The patients were grouped into PGGs 1–5. The number of patients with change in the prognostic group along with follow-up was calculated.Results:There were 143 patients with carcinoma prostate, with a median age of 65 years. The initial GS was revised, and there was a decrease in GS 3 + 4 from 13.9% to 9% and increase in 4 + 3 from 19.6% to 23.8%. There was upgradation of PGG in 11 (7.69%) biopsies; with PGG from 1 to 2 in one; 2to 3 in eight; and 3to 4 in two. Follow-up at 2 years in 22 showed the poor prognoses in the patients who were upgraded to the higher prognostic group.Conclusions:A change in PGG according to the WHO 2016 criteria was assigned in 7.69% biopsies of carcinoma prostate, and it correlated with prognosis.

Neuroendocrine prostate cancer

Neuroendocrine prostate cancer (NEPC) mostly occurs as atreatment-emergent adaptive response under the pressure of intensive androgen deprivation treatment (t-NEPC). Approximately 30-40% of patients with metastatic castration-resistant prostate cancer (mCRPC) also have neuroendocrine involvement. In contrast primary small cell prostate cancer is very rare (<1%). A t‑NEPC should be clinically suspected in patients who have particularly aggressive mCRPC but a disproportionately low prostate-specific antigen (PSA) level and elevated neuroendocrine tumor markers, such as chromograninA and neuron-specific enolase. The initial Gleason score was shown to be an independent factor correlated to the risk of development of t‑NEPC. Treatment is oriented to that of small cell lung cancer. In patients with negative PSA levels, chemotherapy with cisplatin and etoposide is the first line treatment, for which response rates in the range of 30-60% with amedian survival time of usually less than 1year can be achieved. In patients with much higher serum PSA levels, chemotherapy with carboplatin plus docetaxel should be considered.

Long-Term Outcomes Analysis of Low Dose Rate Brachytherapy (LDR-BT) in Clinically T3 High-Risk Prostate Carcinoma

Prior utilization and reporting of outcomes with Low Dose Rate Prostate Brachytherapy (LDR-BT) in patients with prostatic extracapsular extension (T3a) and/or seminal vesicle invasion (T3b) has been limited. Herein, we report the long term clinical outcomes data for patients with cT3a/b disease receiving LDR-BT based treatment approaches and hypothesize that these approaches will achieve acceptable long term biochemical control rates. 99 men (median age: 69.4 years) with cT3a (75%) or cT3b (25%) high-risk prostate adenocarcinoma received definitive LDR-BT (29%) or LDR-BT boost following external beam (EBRT) with I-125 or Pd-103 at a single institution between 1998 and 2007. Median PSA at diagnosis was 11.4 ng/ml with 51% and 49% of men having initial gleason scores of <7 and 8-10, respectively. All patients receiving definitive LDR-BT refused receipt of EBRT. 86% of patients received Androgen Deprivation Therapy. Sources were delivered via a pre-planned, template-based, pre-loaded needle technique. Biochemical relapse free survival (BRFS), Prostate Cancer Specific Mortality (PCSM), and Overall Survival (OS) were calculated using the Kaplan-Meier method with the Phoenix definition (nadir plus 2ng/ml) as definition of failure. Outcomes are reported as estimates (+/- standard error). Cox-Regression analysis was used to compare outcomes between T3a & T3b disease, initial Gleason Scores (6-10) as well as among stratification of initial PSA (iPSA: <10ng/ml, 10-20, >20), and Percent Core Positive rates (<25%, 25-50%, 50-75%, >75%). With a median follow up time of 6.9 years, 7 year BRFS was 65.2% (+/- 5.6%), 7 year PCSM was 9.9% (+/- 3.6%), and 7 year OS was 77.9% (+/- 4.7%) for all patients. No significant difference in BRFS, PCSM or OS rates was present between T3a or T3b disease, initial gleason score, iPSA stratification or percent core positive rates. Men with cT3 high-risk disease achieve excellent biochemical control and survival outcomes with use of LDR-BT based treatment techniques, suggesting that the presence of T3 disease should not be a contraindication to use of LDR-BT. No significant difference in outcomes is present based on initial tumor related characteristics at this follow up period.