Gleason Sum Score Research Articles

Can dynamic contrast-enhanced MR imaging based on radiomics improve the diagnostic efficiency of clinically significant prostate cancer?

Aims/Background Prostate cancer stands out as one of the most prevalent malignant tumours among males. The non-invasive identification of clinically significant prostate cancer via magnetic resonance imaging plays a critical role in circumventing unnecessary biopsies and determining suitable treatment strategies for patients. Our study aimed to evaluate the potential improvement in predictive accuracy for clinically significant prostate cancer by incorporating perfusion data obtained from dynamic contrast-enhanced magnetic resonance imaging acquisition protocols into multiparametric magnetic resonance imaging parameters. Methods Radiomics extracted from perfusion parameters (Ktrans, Kep, Ve) of dynamic contrast-enhanced magnetic resonance imaging were analysed in patients suspected of prostate cancer who underwent 3T multiparametric magnetic resonance imaging between January 2017 and June 2023 in this retrospective study. The pathological findings obtained from biopsy or therapy were categorised into groups based on the Gleason sum score as either clinically significant prostate cancer (Gleason sum score > 7) or non-clinically significant prostate cancer (Gleason sum score ≤ 6). Diagnostic models were constructed using logistic regression analysis, incorporating prostate imaging reporting and data system V2.1 scores and clinical data, with or without radiomics extracted from dynamic contrast-enhanced. The area under curve (AUC) values were compared using the DeLong test. Results Overall, 214 men (clinically significant prostate cancer [n=78] and non-clinically significant prostate cancer [n=136]) were included. The clinical-prostate imaging reporting and data system model demonstrated an AUC of 0.89 (95% confidence interval: 0.84-0.95) in the training cohort and 0.91 (95% confidence interval: 0.84-0.98) in the test cohort. For the clinical-prostate imaging reporting and data system-radscore model, the AUC values were 0.97 (95% confidence interval: 0.95-0.99) for Ktrans, 0.98 (95% confidence interval: 0.96-1.00) for Ve, and 0.96 (95% confidence interval: 0.93-0.98) for Kep in the training cohort, and 0.97 (95% confidence interval: 0.94-1.00) for Ktrans, 0.95 (95% confidence interval: 0.91-1.00) for Ve, and 0.97 (95% confidence interval: 0.94-1.00) for Kep in the test cohort. Radiomics based on perfusion parameters exhibited good diagnostic performance in predicting clinically significant prostate cancer. The clinical-prostate imaging reporting and data system-radscore model demonstrated superior diagnostic capability compared to perfusion-based radiomics or clinical-prostate imaging reporting and data system models alone. Conclusion The application of radiomics, which involves extracting perfusion parameters from dynamic contrast-enhanced imaging, has the potential to enhance diagnostic accuracy for clinically significant prostate cancer.

A Model for Predicting Clinically Significant Prostate Cancer Using Prostate MRI and Risk Factors

PurposeThe aim of this study was to develop and validate a predictive model for clinically significant prostate cancer (csPCa) using prostate MRI and patient risk factors. MethodsIn total, 960 men who underwent MRI from 2015 to 2019 and biopsy either 6 months before or 6 months after MRI were identified. Men diagnosed with csPCa were identified, and csPCa risk was modeled using known patient factors (age, race, and prostate-specific antigen [PSA] level) and prostate MRI findings (location, Prostate Imaging Reporting and Data System score, extraprostatic extension, dominant lesion size, and PSA density). csPCa was defined as Gleason score sum ≥ 7. Using a derivation cohort, a multivariable logistic regression model and a point-based scoring system were developed to predict csPCa. Discrimination and calibration were assessed in a separate independent validation cohort. ResultsAmong 960 MRI reports, 552 (57.5%) were from men diagnosed with csPCa. Using the derivation cohort (n = 632), variables that predicted csPCa were Prostate Imaging Reporting and Data System scores of 4 and 5, the presence of extraprostatic extension, and elevated PSA density. Evaluation using the validation cohort (n = 328) resulted in an area under the curve of 0.77, with adequate calibration (Hosmer-Lemeshow P = .58). At a risk threshold of >2 points, the model identified csPCa with sensitivity of 98.4% and negative predictive value of 78.6% but prevented only 4.3% potential biopsies (0-2 points; 14 of 328). At a higher threshold of >5 points, the model identified csPCa with sensitivity of 89.5% and negative predictive value of 70.1% and avoided 20.4% of biopsies (0-5 points; 67 of 328). ConclusionsThe point-based model reported here can potentially identify a vast majority of men at risk for csPCa, while avoiding biopsy in about 1 in 5 men with elevated PSA levels.

Contemporary validation of cT1a vs. cT1b substaging of incidental prostate cancer.

The cT1a vs. cT1b substratification was introduced in 1992 but never formally tested since. We tested the discriminative ability of cT1a vs. cT1b substaging on cancer-specific survival (CSS) in contemporary incidental prostate cancer (PCa) patients. Incidental (cT1a/cT1b) PCa patients were identified within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015). Kaplan-Meier estimates, as well as uni- and multivariable Cox regression models predicted CSS at five years. Subgroup analyses addressed CSS at five years according to active vs. no local treatment (NLT) as well as Gleason score sum (GS; 6 vs. 7 vs. ≥ 8). We identified a total of 5,155 incidental prostate cancer patients of which 3,035 (59%) were stage cT1a vs. 2,120 (41%) were stage cT1b. In all incidental PCa patients, CSS at five years was 95% (95% CI 0.94-0.96). In cT1a patients, CSS at five years was 98 vs. 90% in cT1b patients (p < 0.001). In multivariable Cox regression analyses, cT1b independently predicted 2.8-fold higher CSM than cT1a (HR 2.5, 95% CI 1.8-3.6, p < 0.001) for incidental PCa patients who underwent NLT. In subgroup analyses, cT1b represented an independent predictor of higher CSM in GS ≥ 8 (HR 3.0, 95% CI 1.4-6.2, p = 0.003), and GS 7 (HR 3.9, 95% CI 1.6-9.7 p = 0.002) patients who underwent NLT. For actively treated patients, cT1b was not independently associated with worse CSM. The historical subclassification of cT1a vs. cT1b in incidental PCa patients displayed a strong ability to discriminate CSS in contemporary GS 7 and GS ≥ 8 patients who underwent NLT. However, no statistically significant difference was recorded in actively treated patients. In consequence, the importance of the current substage stratification predominantly applies to GS ≥ 8 patients who undergo a non-active treatment approach.

La prostatectomía radical retropúbica abierta es todavía una técnica quirúrgica bien establecida para el tratamiento del cáncer de próstata

IntroductionThe surgical treatment options for prostate cancer have changed rapidly, given the expansion of robotics. However, open retropubic radical prostatectomy (ORP) will continue to be performed in areas with financial limitations or with limited access to robotics. The purpose of this study was to determine the long-term oncological outcomes, to categorize complication rates and to examine the early continence rates in patients treated with ORP. MethodsWe identified all patients who underwent ORP at our institution between 2000 and 2020. A standardized pad test was used to determine the early continence rates upon catheter removal, the late continence around a year after surgery was determined by the number of pads per day. The Clavien-Dindo classification was used to report the complication rates. The biochemical recurrence (BCR)-free survival and overall survival (OS) rates were defined using the Kaplan-Meier method and log-rank analysis. Multivariable Cox-regression models were used to test the effect of different factors on biochemical recurrence. ResultsWe analyzed 1095 patients. The median follow-up was 93.4months. An overall 10-year BCR-free survival and OS of 73% and 82% respectively was found. A complication rate for Clavien Dindo ≥3 was seen in 4.8% of patients. The early continence rate was 81.4% and the late continence 89.1%. Preoperative PSA level, Gleason score sum, pT stage, lymph node status, and surgical margin status were independent predictors of BCR (P<.001). Limitations include retrospective and single centre study design. ConclusionsORP is a surgical procedure that provides excellent oncological- and early continence-rates.

Open retropubic radical prostatectomy: Still a well-established surgical technique for prostate cancer management

IntroductionThe surgical treatment options for prostate cancer have changed rapidly, given the expansion of robotics. However, open retropubic radical prostatectomy (ORP) will continue to be performed in areas with financial limitations or with limited access to robotics. The purpose of this study was to determine the long-term oncological outcomes, to categorize complication rates and to examine the early continence rates in patients treated with ORP. MethodsWe identified all patients who underwent ORP at our institution between 2000 and 2020. A standardized pad test was used to determine the early continence rates upon catheter removal, the late continence around a year after surgery was determined by the number of pads per day. The Clavien-Dindo classification was used to report the complication rates. The biochemical recurrence (BCR)-free survival and overall survival (OS) rates were defined using the Kaplan–Meier method and log-rank analysis. Multivariable Cox-regression models were used to test the effect of different factors on biochemical recurrence. ResultsWe analyzed 1095 patients. The median follow-up was 93.4 months. An overall 10-year BCR-free survival and OS of 73% and 82% respectively was found. A complication rate for Clavien Dindo≥3 was seen in 4.8% of patients. The early continence rate was 81.4% and the late continence 89,1%. Preoperative PSA level, Gleason score sum, pT stage, lymph node status, and surgical margin status were independent predictors of BCR (p<0.001, 95% CI). Limitations include retrospective and single center study design. ConclusionsORP is a surgical procedure that provides excellent oncological- and early continence-rates.

Abstract 2210: The study of age and race genetic signatures of prostate cancer with formalin fixed paraffin embedded (FFPE) samples

Abstract Objectives: Diagnosis with prostate cancer (PCa) at younger age is a serious challenge in Military Health System. PCa onset at younger age is more likely to be aggressive in African American (AA) population. Also, application of formalin fixed paraffin embedded (FFPE) tissue in RNA based study was significantly hindered due to poor quality/quantity of RNA in archived pathology slides. This study is aimed to examine age/race associated gene signatures in military cohort with high representation of AA and younger population in FFPE samples for potential genetic mechanisms of health disparities and broaden tissue sample availability. Methods: A cohort of 41 Caucasian American (CA) and 20 AA non-familial PCa patients from the biospecimen bank of CPDR, WRNMMC were used. Specimens donated by radical prostatectomy patients who provided written consent and protocols approved by Institutional Review Boards. Total RNA was extracted from tumor and the adjacent normal epithelium of whole-mount FFPE tissue of matched specimens. Differential gene expression, in tumor versus normal tissues, between younger and older AA and CA patients were analyzed by NanoString using a customized CodeSet of 151 probes. The panel designed to detect 135 target transcripts, compiled from 34 genes implicated/associated with PCa progression, 27 PCa specific gene fusions, 25 cancer-associated genes, and 5 genes encoding ETS-family of transcription factors. The 27 over-expressed genes and 17 under-expressed genes in PCa were included as comparison to matched, benign epithelium. Additionally, 5 prostate stroma or epithelium specific genes were selected as control and 11 housekeeping genes were included for biological normalization. Results: The differentially expressed genes related to tumor-normal differences between AA older (66-73 years) and younger (42-58 years) as well as CA older and younger PCa patients with moderate Gleason score (3+3 and 3+4) sum were identified. After controlling for false discovery rates, panel of nine genes (ANXA2, C-MYC, VEGFR1, ERG, NPY, PSMA/FOLH1, TWIST1, MAOA, MYCN) uniquely associated with age/race were identified. Tumor vs normal ratios of ANXA2 and C-MYC expression in prostate tumors of older and younger patients were significantly enhanced. We found a clear association of VEGFR1 gene expression with CA young and c-MYC gene with AA young PCa. Conclusions: Using age/race as endpoint, we identified ANXA2, c-MYC and VEGFR1 as age and race associated PCa gene. Our findings highlight distinct racial and age-related differences and addresses the clinical utility of available genetic tests across old and young AA and CA men, which needs to be further validated in lager cohort. Further, our study also highlighted the utilization of FFPE tissue for NanoString assay and subsequent genetic signature analyses. Citation Format: Shashwat Sharad, Darryl Nousome, Gregory T. Chesnut, Hua Li. The study of age and race genetic signatures of prostate cancer with formalin fixed paraffin embedded (FFPE) samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2210.

Defining more precisely the effects of docetaxel plus ADT for men with mHSPC: Meta-analysis of individual participant data from randomized trials.

5070 Background: Adding docetaxel to androgen deprivation therapy(ADT) improves survival in metastatic, hormone-sensitive prostate cancer (mHSPC), but uncertainty remains about who benefits most. To investigate this thoroughly and reliably, the STOPCAP M1 collaborationconducted a meta-analysis of individual participant data (IPD) from relevant trials. Methods: Methods were included in a registered protocol ( CRD42019140591 ). Updated IPD from the GETUG-15, CHAARTED and STAMPEDE trials were harmonised and checked. The main outcomes were overall survival (OS), progression-free survival (PFS) and failure-free survival (FFS). Overall pooled effects were estimated using intention-to-treat, 2-stage, fixed-effect meta-analysis, adjusted for age, PSA, Gleason sum score, performance status, and timing of metastatic disease (missing covariate values imputed), with 1-stage and random-effects sensitivity analyses. We assessed subgroup effects using 2-stage, fixed-effect meta-analysis of within-trial interactions, adjusted for the same covariates. We based these on PFS to maximise power, and OS whenever interactions were found. To explore multiple subgroup interactions, and to derive subgroup-specific absolute treatment effects, we used 1-stage, flexible parametric modelling and standardisation. Results: We obtained IPD for all 2261 men randomised, with median FU of 6 years (all patients). There were clear relative benefits of docetaxel on OS (HR = 0.79, 95% CI 0.70 to 0.88, p&lt;0.0001), PFS (HR = 0.70, 95% CI 0.63 to 0.77, p&lt;0.0001) and FFS (HR = 0.64, 95% CI 0.58 to 0.71, p&lt;0.0001). With evidence of non-proportional hazards, we also estimated 5-year absolute differences: OS 10% (95% CI 6 to 15%), PFS 9% (95% CI 5 to 13%) and FFS 9% (95% CI 6 to 12%). The relative effect of docetaxel on PFS differed by volume of metastases (interaction p=0.027; high volume HR = 0.60, 95% CI 0.52 to 0.68; low volume HR = 0.78, 95% CI 0.64 to 0.94), and timing of metastatic disease (interaction p=0.077; synchronous HR = 0.67, 95% CI 0.60 to 0.75; metachronous HR = 0.89, 95% CI 0.67 to 1.18). OS results were similar. When metastatic disease volume and timing were combined, docetaxel appeared to improve PFS and OS for all men, except those with low volume, metachronous disease (Table). Conclusions: This IPD meta-analysis provides the most detailed assessment of the effects of docetaxel for mHSPC, and suggests that men with low volume, metachronous disease should be managed differently to those with other types of metastatic disease. [Table: see text]

Effect of Prostate MRI Interpretation Experience on PPV Using PI-RADS Version 2: A 6-Year Assessment Among Eight Fellowship-Trained Radiologists.

BACKGROUND. Understanding the effect of specific experience in prostate MRI interpretation on diagnostic performance would help inform the minimum interpretation volume to establish proficiency. OBJECTIVE. The purpose of this article is to assess for an association between increasing experience in prostate MRI interpretation and change in radiologist-level PPVs for PI-RADS version 2 (v2) categories 3, 4, and 5. METHODS. This retrospective study included prostate MRI examinations performed between July 1, 2015, and August 13, 2021, that were assigned a PI-RADS v2 category of 3, 4, or 5 and with an MRI-ultrasound fusion biopsy available as the reference standard. All examinations were among the first 100-200 prostate MRI examinations interpreted using PI-RADS v2 by fellowship-trained abdominal radiologists. Radiologists received feedback through a quality assurance program. Radiologists' experience levels were classified using progressive subsets of 50 interpreted examinations. Change with increasing experience in distribution of individual radiologists' whole-gland PPVs for Gleason sum score 7 or greater prostate cancer, stratified by PI-RADS category, was assessed by hierarchic linear mixed models. RESULTS. The study included 1300 prostate MRI examinations in 1037 patients (mean age, 66 ± 7 [SD] years), interpreted by eight radiologists (median, 13 years of postfellow-ship experience; range, 5-22 years). Aggregate PPVs were 20% (68/340) for PI-RADS category 3, 49% (318/652) for category 4, and 71% (220/308) for category 5. Interquartile ranges (IQRs) of PPVs overlapped for category 4 (51%; IQR, 42-60%) and category 5 (70%; IQR, 54-75%) for radiologists' first 50 examinations. IQRs of PPVs did not overlap between categories of greater experience; for example, at the 101-150 examination level, PPV for category 3 was 24% (IQR, 20-29%), category 4 was 55% (IQR, 54-63%), and category 5 was 81% (IQR, 77-82%). Hierarchic modeling showed no change in radiologists' absolute PPV with increasing experience (category 3, p = .27; category 4, p = .71; category 5, p = .38). CONCLUSION. Absolute PPVs at specific PI-RADS categories did not change during radiologists' first 200 included examinations. However, resolution of initial overlap in IQRs indicates improved precision of PPVs after the first 50 examinations. CLINICAL IMPACT. If implementing a minimum training threshold for fellowship-trained abdominal radiologists, 50 prostate MRI examinations may be sufficient in the context of a quality assurance program with feedback.

Defining factors predictive of persistent climacturia after radical prostatectomy

ABSTRACT Introduction Climacturia (Cl) is defined as the involuntary leakage of urine around the time of orgasm. Cl is a common clinical condition after radical prostatectomy (RP). Cl is a barrier to sexual satisfaction. Rates as high as 60% have been reported with little data on the chronology of recovery. Objective This study aimed to evaluate the natural history of CI after RP. Methods Men who underwent RP and completed a proprietary sexual incontinence questionnaire at 12 and 24 months (±3 months) constituted the study sample. Pre or postop ADT or radiation therapy were exclusions. We assessed demographics, comorbidities, baseline testosterone (T), pre-RP prostate specific antigen (PSA), Gleason group, nerve sparing status (NSS), and the presence of stress urinary incontinence (SUI) post-RP. Primary end-point was Cl rate at 12 and 24 months post-RP. Predictors of Cl were analyzed using a series of logistic regression models. Factors entered into the model included age, diabetes, smoking history, baseline T, baseline PSA, Gleason score sum, and NSS score. Results Data on 152 men were analyzed. Mean age 61±8 years. 45% had hypertension, 60% hyperlipidemia, 10% had diabetes, 18% obstructive sleep apnea, 8% were current smoker, and 27% former smokers. Baseline T and PSA were 421±176 ng/dL and 7±6 ng/mL. The median Gleason score was 7, 82% of patients had bilateral NSS, 13% unilateral. Median NSS score was 3 (IQR 2, 4). Cl prevalence at 12 and 24 months post-surgery were 38% and 39%. No patient characteristics were associated with CI at either 12 or 24 months post-RP. Conclusion Cl is highly prevalent at 12 months post RP and when present at this juncture appears to be unlikely to recover. Disclosure Work supported by industry: no.

Defining Factors Predictive of Persistent Climacturia After Radical Prostatectomy

ABSTRACT Introduction Climacturia (Cl) is defined as the involuntary leakage of urine around the time of orgasm. Cl is a common clinical condition after radical prostatectomy (RP). Cl is a barrier to sexual satisfaction. Rates as high as 60% have been reported with little data on the chronology of recovery. Objective This study aimed to evaluate the natural history of CI after RP. Methods Men who underwent RP and completed a proprietary sexual incontinence questionnaire at 12 and 24 months (±3 months) constituted the study sample. Pre or postop ADT or radiation therapy were exclusions. We assessed demographics, comorbidities, baseline testosterone (T), pre-RP prostate specific antigen (PSA), Gleason group, nerve sparing status (NSS), and the presence of stress urinary incontinence (SUI) post-RP. Primary end-point was Cl rate at 12 and 24 months post-RP. Predictors of Cl were analyzed using a series of logistic regression models. Factors entered into the model included age, diabetes, smoking history, baseline T, baseline PSA, Gleason score sum, and NSS score. Results Data on 152 men were analyzed. Mean age 61±8 years. 45% had hypertension, 60% hyperlipidemia, 10% had diabetes, 18% obstructive sleep apnea, 8% were current smoker, and 27% former smokers. Baseline T and PSA were 421±176 ng/dL and 7±6 ng/mL. The median Gleason score was 7, 82% of patients had bilateral NSS, 13% unilateral. Median NSS score was 3 (IQR 2, 4). Cl prevalence at 12 and 24 months post-surgery were 38% and 39%. No patient characteristics were associated with CI at either 12 or 24 months post-RP. Conclusions Cl is highly prevalent at 12 months post RP and when present at this juncture appears to be unlikely to recover. Disclosure No

Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol

Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol

Presenting Pattern and Treatment Modalities of Prostate Cancer in Nicrh

Objective: The aim was to describe the clinicopathological presentation of prostate cancer and the treatment modality in patients seen in Uro-oncology department of National Institute of Cancer Research &amp; Hospital (NICRH), Bangladesh. Methods: Data were collected prospectively from all patients with diagnosed prostate cancer and managed in Uro-oncology department of NICRH from January 2016 to December 2017. Patient’s age, clinical presentation, prostate specific antigen(PSA) level, mode of diagnosis, Gleason sum score, stage of the disease at presentation and modality of treatment were recorded and analyzed. Results: There were 407 cases of histologically proven prostate cancer. Mean patient age was 69 years. About 87% presented as diagnosed prostate cancer. Twenty one(5%) patient presented with features of metastasis with unknown primary , we confirmed after prostate biopsy. About 77% of patients had a serum PSA above 20 ng/ml. Gleason sum score was 8 or more in 46% of patients. Metastases were found at the time of presentation in 85% of patients. Ten (2.5%) patients underwent radical radiotherapy, while two patients had radical prostatectomy. Most (68%) of the 347 patients who required androgen deprivation therapy had surgical orchiectomy. Conclusion: Bangladesh appear to be having a low incidence of prostate cancer, but a larger proportion of advanced and high grade cancers in comparison to the UK and USA. Although genetic differences may exist, a dietary or an environmental factor is more likely to be the cause for these changes. The protective effect of this factor appears to wane as South Asians emigrate and live in UK and USA. Bangladesh Journal of Urology, Vol. 21, No. 2, July 2018 p 56-61

High spatiotemporal resolution dynamic contrast-enhanced MRI improves the image-based discrimination of histopathology risk groups of peripheral zone prostate cancer: a supervised machine learning approach.

To assess if adding perfusion information from dynamic contrast-enhanced (DCE MRI) acquisition schemes with high spatiotemporal resolution to T2w/DWI sequences as input features for a gradient boosting machine (GBM) machine learning (ML) classifier could better classify prostate cancer (PCa) risk groups than T2w/DWI sequences alone. One hundred ninety patients (68 ± 9years) were retrospectively evaluated at 3T MRI for clinical suspicion of PCa. Included were 201 peripheral zone (PZ) PCa lesions. Histopathological confirmation on fusion biopsy was matched with normal prostate parenchyma contralaterally. Biopsy results were grouped into benign tissue and low-, intermediate-, and high-risk groups (Gleason sum score 6, 7, and > 7, respectively). DCE MRI was performed using golden-angle radial sparse MRI. Perfusion maps (Ktrans, Kep, Ve), apparent diffusion coefficient (ADC), and absolute T2w signal intensity were determined and used as input features for building two ML models: GBM with/without perfusion maps. Areas under the receiver operating characteristic curve (AUC) values for correlated models were compared. For the classification of benign vs. malignant and intermediate- vs. high-grade PCa, perfusion information added relevant information (AUC values 1 vs. 0.953 and 0.909 vs. 0.700, p < 0.001 and p = 0.038), while no statistically significant effect was found for low- vs. intermediate- and high-grade PCa. Perfusion information from DCE MRI acquisition schemes with high spatiotemporal resolution to ML classifiers enables a superior risk stratification between benign and malignant and intermediate- and high-risk PCa in the PZ compared with classifiers based on T2w/DWI information alone. • In the recent guidelines, the role of DCE MRI has changed from a mandatory to recommended sequence. • DCE MRI acquisition schemes with high spatiotemporal resolution (e.g., GRASP) have been shown to improve the diagnostic performance compared with conventional DCE MRI sequences. • Using perfusion information acquired with GRASP in combination with ML classifiers significantly improved the prediction of benign vs. malignant and intermediate- vs. high-grade peripheral zone prostate cancer compared with non-contrast sequences.

LBA48_PR - Adjuvant or salvage radiotherapy for the treatment of localised prostate cancer? A prospectively planned aggregate data meta-analysis

LBA48_PR - Adjuvant or salvage radiotherapy for the treatment of localised prostate cancer? A prospectively planned aggregate data meta-analysis

Clinical features of bone metastasis with extraosseous soft-tissue mass in prostate cancer patients

Objective: This study aimed to compare the differences in the clinical features of prostate cancer (PC) bone metastases (PCBMs) with and without extraosseous soft-tissue masses (ESTMs). Methods: Among 720 consecutive patients with histopathologically or clinically diagnosed PC, PCBMs were identified in 48 (7%) patients at initial diagnosis before receiving treatment. CT images of PCBMs were assessed and classified into two groups: PCBMs with and without ESTMs. Clinical features of PCBMs with and without ESTMs were compared. Results: We found ESTMs in 15 (31%) patients diagnosed with PCBMs, and 33 (69%) patients diagnosed with PCBMs did not have ESTMs. The initial prostate-specific antigen (PSA) levels (median, 1031 vs 247 ng ml−1; p &lt; 0.05) and PSA reduction rates (median, 99.97 vs 99.40 %; p &lt; 0.05) were significantly greater in PCBMs with ESTMs than in PCBMs without ESTMs. No significant differences were observed in terms of age, Gleason sum score, PSA nadir, time from the initiation of therapy to PSA nadir, PSA doubling time, PSA progression-free survival, or overall survival between patients having PCBMs with and without ESTMs. Conclusion: Both initial PSA levels and PSA reduction rates were higher in PCBMs with ESTMs than in PCBMs without ESTMs; however, no significant differences were observed in other clinical features. Advances in knowledge: ESTMs in patients with PCBMs were not a poor prognostic factor.

High-dose intensity-modulated radiation therapy as primary treatment of prostate cancer: genitourinary/gastrointestinal toxicity and outcomes, a single-institution experience.

Prostatectomy, radiotherapy and watchful waiting are the main therapeutic options available for local stage of prostate cancer (PCa). We report our experience on 394 patients affected by prostate cancer primarily treated with high-dose, image-guided, IMRT, focusing on gastrointestinal, genitourinary toxicities and biochemical control. From July 2003 to August 2014, 394 patients were treated with radical high-dose radiotherapy (HDRT) for prostate cancer; the mean total radiation dose was 79Gy in standard fractions. Hormonal therapy (HT) was administered to 7.6% of low-risk patients, to 20.3% of intermediate-risk patients and to 72% of high-risk patients. Patients were evaluated for biochemical failure, local recurrence (LR) and metastases. Ninety-seven patients (26.65%) developed acute GU toxicity at the medium dose of 25.4Gy, grade 1 (G1) or grade 2 (G2) in 94 cases. Only 16 patients (4.06%) reported chronic GU toxicity (G1 or G2), and one case developed G3 cystitis. No G3 GI acute and late toxicity were detected. Fifty-six (14.2%) patients experienced LR, 26 (6.6%) developed metastases and 70 patients (17.8%) were deceased. Gleason sum score > 7 was predictive for worse overall survival (GS = 7 was borderline) and for metastasis. No factors resulted predictive for local relapse. HT pre-RT had been demonstrated as a negative predictor for OS and DFS-DM. Data confirm the safety of HDRT for PCa. Treatment was efficient with low toxicity profile. Moreover, continued technologic advancements, as image-guided radiotherapy, could lead to further reduction in toxicity, thus increasing the therapeutic index.

Differential immunohistochemical expression of AMACR and ERG in prostatic lesions

Introduction Alpha-methylacyl-CoA (AMACR) is an enzyme of the mitochondria and perixosomes. It was found that it showed great overexpression in prostatic adenocarcinoma, even with minimal foci. TMPRSS2/ERG fusion is one of the common genetic anomalies affecting PCa. A great correlation between positive immunohistochemical (IHC) expression for ERG and the state of fusion has been found, but the diagnostic and prognostic importance of ERG IHC remains undetected. This study aimed to evaluate the differential diagnostic and prognostic significance of both AMACR and ERG in PCa with correlation to the clinicopathological variables.Materials and methods TThe authors reviewed 70 prostatic lesions. Prostatic adenocarcinoma (50 cases), prostatic intraepithelial neoplasia (PIN) (15 with high-grade PIN, five with low-grade PIN), and benign prostatic hyperplasia (10 cases) that were used as a control. Immunohistochemical staining for AMACR and ERG was done. Follow-up of the cases for 18 months was also done.Results A statistically significant difference in the expression of ERG among the examined cases was found. It was negative in control benign prostatic hyperplasia and low-grade PIN cases), positive in 20% of high-grade PIN, and 74% of prostatic adenocarcinoma cases (P<0.01). No statistically significant correlation was found between ERG expression and tumor volume, Gleason sum score, stage, surgical margin, presence of lymphovascular invasion, perinural invasion, distant metastasis, and survival (P>0.05). Regarding AMACR expression, a statistically significant difference in the expression of AMACR among the examined cases was found (negative in benign prostatic hyperplasia, and low PIN cases) to be positive in 33.3% of high-grade PIN and in 62% of prostatic adenocarcinoma cases (P<0.01). A statistically significant correlation was found between AMACR expression and tumor volume, Gleason sum score, surgical margin, presence of lymphovascular invasion, and survival (P<0.05).Conclusion The study provides an additional evidence that IHC expression of AMACR has a role in prostatic carcinoma development. IHC expression of AMACR was absent in benign prostatic lesions. AMACR is an essential tumor marker for the diagnosis and prognosis of prostatic lesions. IHC expression of ERG may have a role in the diagnosis and biological stratification of prostate cancer.

Development and Validation of a Novel Prognostic Model for Predicting Overall Survival in Treatment-naïve Castration-sensitive Metastatic Prostate Cancer

BackgroundThere has been growth in the treatment options for castration-sensitive metastatic prostate cancer (mPCa), but without clear guidance for risk stratification. ObjectiveTo identify clinical parameters associated with overall survival (OS) and establish a prognostic model for use with treatment-naïve castration-sensitive mPCa. Design, setting, and participantsA retrospective review of 304 patients treated at Kyoto University Hospital was performed. A prognostic model was created using clinical parameters associated with OS. The model was externally validated in an independent cohort of 520 patients. Outcome measurements and statistical analysisMultivariable analysis was performed to identify the clinical parameters associated with OS. Risk scores were calculated using Cox proportional hazards analysis for each combination of risk factors, and patients were grouped into categories based on those scores. Results and limitationsOver 80% of the cohort had a Gleason sum score ≥8. The median OS was 53mo among patients with CHAARTED high-volume PCa (n=172) and 131mo among those with low-volume PCa (n=100). Independent factors associated with OS were extent of disease score ≥2 or the presence of liver metastasis; lactate dehydrogenase >250U/L; and a primary Gleason score of 5. The median OS for the high-, intermediate-, and low-risk groups according to the new model were 28mo, 59mo, and not reached, respectively; the corresponding values in the validation cohort were 41mo, 63mo, and not reached. Harrell's C-index was 0.649. ConclusionsOur simple and reproducible prognostic model for treatment-naïve castration-sensitive mPCa could aid in risk stratification and treatment selection. Patient summaryWe identified clinical parameters associated with prognosis in castration-sensitive metastatic prostate cancer and established a reproducible prognostic model that could be used to guide treatment decisions.

Effects of Progressive Resistance Training on Post-Surgery Incontinence in Men with Prostate Cancer.

We evaluated the efficacy of progressive resistance training of the pelvic floor muscle for post-prostatectomy incontinence. In this prospective study, 59 patients who underwent radical prostatectomy were evaluated preoperatively. Continence was sequentially assessed within 2 weeks postoperatively, and an exercise regimen was initiated at 6- and 12-weeks. The primary outcome was continent status and the secondary outcome was changes in muscle strength and endurance after the exercise intervention. Continence was defined as no urine loss in a 1h pad test. A total of 59 patients participated in this study. Six patients dropped out of the study because of non-compliance and orthopedic problems. Of the remaining 53 patients, 31 (58.5%) achieved pad-free continence at 12 weeks postoperatively. The patients were divided into two groups based on their continence status, and no statistically significant difference was observed in age, body mass index, prostate volume, prostate-specific antigen, pathological Gleason score sum, and pathological T stage. Meanwhile, preoperative maximal urethral closure pressure and change in hip extensor muscle strength and endurance during the 12-week exercise program were significantly higher in the continent group. In multivariate analysis, change in hip extensor muscle strength was the only significant parameter predicting achievement of continence status (Odds ratio, 1.039; p = 0.045). The changes in hip extensor muscle strength in the current exercise program was an independent predictor of continence status after radical prostatectomy. A large-scale prospective study on the relationship between extensor muscle strength and urinary incontinence should be explored in future.

Active Surveillance for Prostate Cancer in a Real-life Cohort: Comparing Outcomes for PRIAS-eligible and PRIAS-ineligible Patients

BackgroundIn daily practice, a wider range of patients with prostate cancer (PCa) are selected for active surveillance (AS) compared to those in AS trials, including higher-risk patients. However, less is known about the outcomes for off-protocol selected PCa patients who opt for AS. ObjectiveTo compare AS outcomes for higher-risk patients and very low-risk patients in a large cohort of patients diagnosed with PCa. Design, setting, and participantsPatients diagnosed with PCa between 2008 and 2015 with clinical stage ≥T1c and managed with AS at six large teaching hospitals. InterventionAS included regular prostate-specific antigen (PSA) testing (every 3–6 mo) and a confirmatory biopsy 1 yr after diagnosis and every 3 yr thereafter. Outcomes measurements and statistical analysisUsing the inclusion criteria of the PRIAS study, outcomes for PRIAS-eligible patients (ie, cT1c–T2, Gleason sum score ≤6, ≤2 positive biopsy cores, PSA ≤10 ng/ml, and PSA density <0.2 ng/ml/ml) were compared to outcomes for PRIAS-ineligible patients. Unfavourable outcomes following deferred surgery, biochemical recurrence, and risk of metastasis were calculated using univariate and multivariate Cox regression analyses. Time to tumour progression was established using survival analysis. Results and limitationsOf the 1000 patients included and managed with AS, almost half of the patients (49%) had higher-risk disease characteristics than the PRIAS inclusion criteria. PRIAS-ineligible patients discontinued AS because of tumour progression significantly earlier than PRIAS-eligible patients (hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.44–2.11); they also had a higher risk of positive surgical margins (odds ratio [OR] 2.15, 95% CI 1.11–4.17) and unfavourable pathological findings (OR 3.20, 95% CI 1.61–6.35) following deferred radical prostatectomy. PSA density ≥0.2 ng/ml/ml was the most important individual predictor and, in addition to a higher risk of tumour progression and unfavourable surgical outcomes, was also associated with a significantly higher risk of biochemical progression following deferred radical prostatectomy (OR 3.26, 95% CI 1.23–8.64). In the overall population, PSA density ≥0.2 ng/ml/ml was also associated with a higher risk of metastasis (HR 2.71, 95% CI 1.23–5.96). ConclusionsIn this cohort, approximately half of the patients did not meet the inclusion criteria of the PRIAS study. These patients had a two- to threefold higher risk of disease progression and unfavourable outcomes following deferred prostatectomy. PSA density is an important individual predictor of unfavourable outcomes and should be taken into account when selecting patients for AS. Patient summaryA large proportion of patients with prostate cancer on active surveillance are not in the lowest risk group. These patients have a higher risk of experiencing tumour progression to a stage requiring curative intervention. They also have worse disease prognosis compared to patients on active surveillance in the lowest risk group.