Low-risk Prostate Cancer Patients Research Articles

ESTRO-ACROP recommendations for evidence-based use of androgen deprivation therapy in combination with external-beam radiotherapy in prostate cancer

Background and purposeThere is no consensus concerning the appropriate use of androgen deprivation therapy (ADT) during primary and postoperative external-beam radiotherapy (EBRT) in the management of prostate cancer (PCa). Thus, the European Society for Radiotherapy and Oncology (ESTRO) Advisory Committee for Radiation Oncology Practice (ACROP) guidelines seeks to present current recommendations for the clinical use of ADT in the various indications of EBRT. Material and methodsA literature search was conducted in MEDLINE PubMed that evaluated EBRT and ADT in prostate cancer. The search focused on randomized, Phase II and III trials published in English from January 2000 to May 2022. In case topics were addressed in the absence of Phase II or III trials, recommendations were labelled accordingly based on the limited body of evidence. Localized PCa was classified according to D’Amico et al. classification in low-, intermediate and high risk PCa. The ACROP clinical committee identified 13 European experts who discussed and analyzed the body of evidence concerning the use of ADT with EBRT for prostate cancer. ResultsKey issues were identified and are discussed: It was concluded that no additional ADT is recommended for low-risk prostate cancer patients, whereas for intermediate- and high-risk patients four to six months and two to three years of ADT are recommended. Likewise, patients with locally advanced prostate cancer are recommended to receive ADT for two to three years and when ≥ 2 high-risk factors (cT3-4, ISUP grade ≥ 4 or PSA ≥ 40 ng/ml) or cN1 is present ADT for three years plus additional Abiraterone for two years is recommended. For postoperative patients no ADT is recommended for adjuvant EBRT in pN0 patients whereas for pN1 patients adjuvant EBRT with long-term ADT is performed for at least 24 to 36 months. In the setting of salvage EBRT ADT is performed in biochemically persistent PCa patients with no evidence of metastatic disease. Long-term ADT (24 months) is recommended in pN0 patients with high risk of further progression (PSA ≥ 0.7 ng/ml and ISUP grade group ≥ 4) and a life expectancy of over ten years, whereas short-term ADT (6 months) is recommended in pN0 patients with lower risk profile (PSA < 0.7 ng/ml and ISUP grade group 4). Patients considered for ultra-hypofractionated EBRT as well as patients with image based local recurrence within the prostatic fossa or lymph node recurrence should participate in appropriate clinical trials evaluating the role of additional ADT. ConclusionThese ESTRO-ACROP recommendations are evidence-based and relevant to the use of ADT in combination with EBRT in PCa for the most common clinical settings.

Adverse Pathology after Radical Prostatectomy of Patients Eligible for Active Surveillance-A Summary 7 Years after Introducing mpMRI-Guided Biopsy in a Real-World Setting.

Over the last decade, active surveillance (AS) of low-risk prostate cancer has been increasing. The mpMRI fusion-guided biopsy of the prostate (FBx) is considered to be the gold standard in preoperative risk stratification. However, the role of FBx remains unclear in terms of risk stratification of low-risk prostate cancer outside high-volume centers. The aim of this study was to evaluate adverse pathology after radical prostatectomy (RP) in a real-world setting, focusing on patients diagnosed with Gleason score (GS) 6 prostate cancer (PCa) and eligible for AS by FBx. Between March 2015 and March 2022, 1297 patients underwent FBx at the Department of Urology, Ludwig-Maximilians-University of Munich, Germany. MpMRI for FBx was performed by 111 different radiology centers. FBx was performed by 14 urologists from our department with different levels of experience. In total, 997/1297 (77%) patients were diagnosed with prostate cancer; 492/997 (49%) of these patients decided to undergo RP in our clinic and were retrospectively included. Univariate and multivariable logistic regression analyses were performed to evaluate clinical and histopathological parameters associated with adverse pathology comparing FBx and RP specimens. To compare FBx and systematic randomized biopsies performed in our clinic before introducing FBx (SBx, n = 2309), we performed a propensity score matching on a 1:1 ratio, adjusting for age, number of positive biopsy cores, and initial PSA (iPSA). A total of 492 patients undergoing FBx or SBx was matched. In total, 55% of patients diagnosed with GS 6 by FBx were upgraded to clinically significant PCa (defined as GS ≥ 7a) after RP, compared to 52% of patients diagnosed by SBx (p = 0.76). A time delay between FBx and RP was identified as the only correlate associated with upgrading. A total of 5.9% of all FBx patients and 6.1% of all SBx patients would have been eligible for AS (p > 0.99) but decided to undergo RP. The positive predictive value of AS eligibility (diagnosis of low-risk PCa after biopsy and after RP) was 17% for FBx and 6.7% for SBx (p = 0.39). In this study, we show, in a real-world setting, that introducing FBx did not lead to significant change in ratio of adverse pathology for low-risk PCa patients after RP compared to SBx.

Economic value of knowing BRCA status: BRCA testing for prostate cancer prevention and optimal treatment

ABSTRACT Background We aimed to estimate the incremental lifetime effects, costs, and net-monetary-benefit (NMB) of knowing BRCA information by testing of patients with low-risk localized prostate cancer (PCa) in the US and guiding subsequent screening and treatment, and the cumulative savings or losses of yearly cohort testing over 16 years. We compared two strategies: (1)‘with BRCA information’ and (2)‘without BRCA information.’ We also estimated the expected value of perfect information. Methods The incremental NMB (INMB) quantified the monetized benefit per person of knowing BRCA status. The net-monetized-value of knowing BRCA information was estimated by multiplying the INMB with the eligible population. Results The INMBs of knowing BRCA information were $43,357 (payer) and $43,487 (society). in payer and societal perspectives, respectively. Escalated to the eligible patients in 2020, knowing BRCA status resulted in net monetized lifetime value of $1.7 billion (payer and society) for the 2020 cohort; and yielded accumulated net-monetized-value of $28.0 billion (payer) and $28.1 billion (society) over 16 yearly cohorts of eligible PCa patients. Conclusions The economic value of knowing BRCA status for all low-risk localized PCa patients in the US provides short-term and long-term evidence for BRCA testing to screen early and optimize treatment.

Long-Term Biochemical Control of a Prospective Cohort of Prostate Cancer Patients Treated With Interstitial Brachytherapy Versus Radical Prostatectomy

AimsTo report long-term oncological outcomes of men treated prospectively as part of the American College of Surgeons Oncology Group phase III Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial (SPIRIT) at our institution. Materials and methodsIn 2003–2004, patients eligible for SPRIT attended a multidisciplinary educational session, following which they could choose radical prostatectomy, low dose rate brachytherapy (LDR-BT) or randomisation to SPIRIT. Biochemical failure was determined by the accepted definitions of a prostate-specific antigen (PSA) level ≥0.2 ng/ml after radical prostatectomy and the Phoenix definition of PSA ≥2 ng/ml above the nadir after LDR-BT. A sensitivity analysis, using a PSA >0.5 ng/ml to define biochemical failure after LDR-BT and a threshold PSA ≥0.2 ng/ml, was carried out to test the robustness of the results. To account for the competing risk of death, Gray's test was used to test the equality of the cumulative incidence function of biochemical failure between treatment groups. The Kaplan–Meier method was used to estimate overall survival and prostate cancer-specific survival. A P-value ≤0.05 was considered statistically significant. ResultsOf 156 patients, 100 received LDR-BT (15 after randomisation) and 56 underwent radical prostatectomy (15 after randomisation). The median follow-up was 12.6 and 14.7 years for LDR-BT and radical prostatectomy, respectively. The median age was 60 years; the median pre-treatment PSA was 5.5 (interquartile range 4.3–7.1). No significant differences in patient characteristics were found between groups. Two patients received adjuvant radiotherapy after radical prostatectomy. The cumulative incidence function of biochemical failure was 0%, 1.1% and 2.4% at 5, 10 and 15 years, respectively, in the LDR-BT arm versus 8.5%, 15.8% and 15.8% in the radical prostatectomy arm (P < 0.001). These results were consistent when varying the definition of biochemical failure defined as PSA ≥0.5 ng/ml (P = 0.01). At 15 years, overall survival was higher in patients treated with radical prostatectomy compared with those treated with LDR-BT; however, no statistical difference was found in prostate cancer-specific survival. ConclusionIn low-risk prostate cancer patients, LDR-BT offers excellent long-term oncological outcomes comparable with radical prostatectomy, in addition to the previously reported advantage for LDR-BT in urinary and sexual quality of life domains and patient satisfaction.

Prognostic Impact and Clinical Implications of Unfavorable Upgrading in Low-Risk Prostate Cancer after Robot-Assisted Radical Prostatectomy: Results of a Single Tertiary Referral Center.

to evaluate predictors and the prognostic impact of favorable vs. unfavorable tumor upgrading among low-risk prostate cancer (LR PCa) patients treated with robot-assisted radical prostatectomy (RARP). From January 2013 to October 2020, LR PCa patients treated with RARP at our institution were identified. Unfavorable tumor upgrading was defined as the presence of an International Society of Urological Pathology (ISUP) grade group at final pathology &gt; 2. Disease relapse was coded as biochemical recurrence and/or local recurrence and/or presence of distant metastases. Regression analyses tested the association between clinical and pathological features and the risk of unfavorable tumor upgrading and disease relapse. Of the 237 total LR PCa patients, 60 (25.3%) harbored unfavorable tumor upgrading. Disease relapse occurred in 20 (8.4%) patients. Unfavorable upgrading represented an independent predictor of disease relapse, even after adjustment for other clinical and pathological variables. Conversely, favorable tumor upgrading did not show any statistically significant association with PCa relapse. Unfavorable tumor upgrading was associated with tumors being larger (OR: 1.03; p = 0.031), tumors extending beyond the gland (OR: 8.54, p &lt; 0.001), age (OR: 1.07, p = 0.009), and PSA density (PSAD) ≥ 0.15 ng/mL/cc (OR: 1.07, p = 0.009). LR PCa patients with unfavorable upgrading at final pathology were more likely to be older, to have PSAD ≥ 0.15 ng/mL/cc, and to experience disease relapse. Unfavorable tumor upgrading is an issue to consider when counseling these patients to avoid delayed treatments, which may impair cancer-specific survival.

Prostate volume is an independent predictive factor in selecting low-risk prostate patients for active surveillance

PurposeThe outcome of the present study is to determine variables available at the time of diagnosis able to predict disease reclassification in prostate cancer (PCa) patients on active surveillance (AS).Materials and methodsFrom January 2014 to December 2018, 114 consecutive low-risk PCa patients were enrolled in AS protocol according to inclusion criteria: PSA ≤ 10 ng/ml, Gleason score (GS) ≤ 6 or International Society of Urological Pathology (ISUP) Gleason grade group (GG) 1, maximum cancer core length (MCCI) &amp;lt; 50%, and ≤ 2 positive cores on biopsy. Patients were followed with confirmatory and yearly prostate biopsy, semi-annually with prostate-specific antigen (PSA), and digital rectal examination (DRE). Disease reclassification was defined as upgrading biopsy: GS ≥ 3 + 4 = 7 or ISUP GG ≥ 2, more than two positive cores, MCCI &amp;gt; 50%, or changes in serum PSA &amp;gt; 10 ng/ml. Uni- and multivariate Cox proportional hazards regression models, receiver performance curves (ROC), and Kaplan-Meier analysis were performed to characterize AS criteria and identify variables that predict disease reclassification. Finally, decision curve analysis (DCA) was performed to evaluate the net benefit of using PV in addition to standard variables to predict disease reclassification.ResultsPCa was diagnosed by systematic transrectal ultrasound-guided prostate biopsy (TRUS-Bx). The mean (range) follow-up was 32.7 (12-126) months. Disease reclassification occurred in 46 patients (40%). On univariate statistical analysis prostate specific antigen (PSA) (p = 0.05), prostate volume (PV) (p = 0.022), PSA density (PSAD) (p &amp;lt; 0.001) and number of positive cores (p = 0.021) were significant factors for disease reclassification. On the multivariate analysis, PSAD (p &amp;lt; 0.001) and PV (p = 0.003) were the only statistically significant independent variables to predict disease reclassification. A PSAD cut-off of 0.16 ng/ml² and a PV cut-off of 44 ml gave a maximal area under the curve, 0.69 and 0.63, respectively. Kaplan-Meier analysis showed that the median survival free from disease reclassification during AS was almost doubled in patients with PSAD &amp;lt; 0.16 ng/ml2 or PV &amp;gt; 44 ml. DCA showed a positive net benefit and clinical usefulness of the model, including PV, to predict disease reclassification between threshold probabilities of 20-50%.ConclusionsPV and PSAD significantly predicted failure from AS in our patients. Patients with a baseline PV of fewer than 44 ml would be more likely to have disease reclassification and unsuitable for acceptable AS protocols. Therefore, we believe that PV may help to select PCa patients for AS, especially in populations where the use of mpMRI is limited.

Pattern of Radiotherapy Treatment in Low-Risk, Intermediate-Risk, and High-Risk Prostate Cancer Patients: Analysis of National Cancer Database.

In this study, the utilization rates and survival outcomes of different radiotherapy techniques are compared in prostate cancer (PCa) patients stratified by risk group. We analyzed an extensive data set of N0, M0, non-surgical PCa patients diagnosed between 2004 and 2015 from the National Cancer Database (NCDB). Patients were grouped into six categories based on RT modality: an intensity-modulated radiation therapy (IMRT) group with brachytherapy (BT) boost, IMRT with/without IMRT boost, proton therapy, stereotactic body radiation therapy (SBRT), low-dose-rate brachytherapy (BT LDR), and high-dose-rate brachytherapy (BT HDR). Patients were also stratified by the National Comprehensive Cancer Network (NCCN) guidelines: low-risk (clinical stage T1-T2a, Gleason Score (GS) ≤ 6, and Prostate-Specific Antigen (PSA) &lt; 10), intermediate-risk (clinical stage T2b or T2c, GS of 7, or PSA of 10-20), and high-risk (clinical stage T3-T4, or GS of 8-10, or PSA &gt; 20). Overall survival (OS) probability was determined using a Kaplan-Meier estimator. Univariate and multivariate analyses were performed by risk group for the six treatment modalities. The most utilized treatment modality for all PCa patients was IMRT (53.1%). Over the years, a steady increase in SBRT utilization was observed, whereas BT HDR usage declined. IMRT-treated patient groups exhibited relatively lower survival probability in all risk categories. A slightly better survival probability was observed for the proton therapy group. Hormonal therapy was used for a large number of patients in all risk groups. This study revealed that IMRT was the most common treatment modality for PCa patients. Brachytherapy, SBRT, and IMRT+BT exhibited similar survival rates, whereas proton showed slightly better overall survival across the three risk groups. However, analysis of the demographics indicates that these differences are at least in part due to selection bias.

Expanding Active Surveillance Criteria for Low- and Intermediate-risk Prostate Cancer: Can We Accurately Predict the Risk of Misclassification for Patients Diagnosed by Multiparametric Magnetic Resonance Imaging–targeted Biopsy?

Models predicting the risk of adverse pathology (ie, International Society of Urological Pathology [ISUP] grade group ≥3, pT3, and/or pN1) among patients operated by radical prostatectomy (RP) have been proposed to expand active surveillance (AS) inclusion criteria. We aimed to test these models in a set of 1062 low-risk and favorable intermediate-risk prostate cancer (PCa) patients diagnosed by multiparametric magnetic resonance imaging (MRI) and MRI-targeted biopsy. We hypothesized that the inclusion of radiological features into a novel model would improve patient selection. Performance was assessed using discrimination, calibration, and decision curve analysis (DCA). Available models were characterized by poor discrimination (areas under the receiver operating characteristic curve [AUCs] of 59% and 60%), underestimation of predicted risk on calibration plots, and a small amount of net benefit against a probability threshold of 40–50% at the DCA. The development of a novel model slightly improved discrimination (AUC of 63% vs 59%, p = 0.001, and 63% vs 60%, p = 0.07) and net benefit against threshold probabilities of ≥30%. This first multicenter study demonstrated the poor performance of models predicting adverse pathology and that implementation of MRI and MRI-targeted biopsy in this setting was not associated with a clear improvement in patient selection. Patients harboring low-risk or favorable intermediate-risk PCa and candidates for RP cannot be referred accurately to an AS program without a non-negligible risk of misclassification. Patient summaryWe tested prediction models that could expand the selection of prostate cancer patients for active surveillance. Models were inaccurate and associated with a high risk of misclassification despite the implementation of multiparametric magnetic resonance imaging and targeted biopsies.

PE28 - Robot-assisted radical prostatectomy oncological and functional outcomes in low-risk prostate cancer patients eligible for active surveillance

PE28 - Robot-assisted radical prostatectomy oncological and functional outcomes in low-risk prostate cancer patients eligible for active surveillance

Verbalization of Patient-Centered Approach (Based on Medical Consultations with Cancer Patients)

The article is devoted to the study of doctor-patient verbal interaction, carried out in line with the patient-centered approach. The relevance of the study is determined by the need to identify the linguistic means used to organize the doctor-patient verbal interaction and to develop in the patient conscious desire to be involved in the treatment process. It is noted that giving the patient greater autonomy in the decision-making process regarding medical treatment methods, the doctor is expected to have the communication skills to structure the text of the conversation and to provide the information in a perception-friendly sequence. The object of the study is medical consultations with cancer patients. The purpose of the study is to identify structural components of the dialogues that include linguistic means aimed to verbalize the patient-centered approach. Authentic Russian-language medical consultations with low-risk prostate cancer patients served as the empirical material. The article presents a comparative analysis of approaches to structuring medical consultations based on Russian, English and German languages; identified structural components aimed to inform the patient in accordance with the patient-centered approach, and the examples of their verbal design. The paper draws conclusions about the semantic and linguistic content of the structural components that help to attract the patient to conscious participation in communication and treatment.

Adverse Pathological Findings at Radical Prostatectomy following Active Surveillance: Results from the Movember GAP3 Cohort.

Simple SummaryActive surveillance (AS) is a standard option for low-risk prostate cancer patients wishing to preserve their quality of life by avoiding or delaying radical treatment side effects. We investigated the consequences of postponing radical prostatectomy (RP) according to stringent or more expansive criteria at inclusion in active surveillance. Features at radical prostatectomy of men withdrawn from AS showed that most of them still have favorable pathology. Frequency of unfavorable pathology was associated with wider entry criteria, PSA density (PSAD) and age, and time spent in active surveillance. Nonetheless, they are restricted to local tumor extension and positive surgical margins, but do not include tumor grade or lymph node involvement. The prognostic implications of these findings remain uncertain, and a longer follow-up is needed.Background: Little is known about the consequences of delaying radical prostatectomy (RP) after Active Surveillance (AS) according to stringent or wider entry criteria. We investigated the association between inclusion criteria and rates, and timing of adverse pathological findings (APFs) among patients in GAP3 cohorts. Methods: APFs (GG ≥ 3, pT ≥ 3, pN > 0 and positive surgical margins [R1]) were accounted for in very low-risk (VLR: grade group [GG] 1, cT1, positive cores < 3, PSA < 10 ng/mL, PSA density [PSAD] < 0.15 ng/mL/cm3) and low-risk (LR: GG1, cT1-2, PSA ≤ 10 ng/mL) patients undergoing subsequent RP. The Kaplan–Meier method and log–rank test analyzed APF-free survival. Stratified mixed effects models analyzed association. Results: Out of 21,169 patients on AS, 1742 (VLR: 721; LR: 1021) underwent delayed RP. Most (60.8%) did not have APFs. APFs occurred more frequently (44.6% vs. 31.7%; OR 1.54, p < 0.001) and earlier (median time: 40.3 vs. 62.6 months; p < 0.001) in LR patients, and consisted of pT ≥ 3 (OR 1.47, p = 0.013) or R1 (OR 1.80, p < 0.001), but not of GG ≥ 3 or node involvement. Age (OR 1.05, p < 0.001), PSAD (OR 23.21, p = 0.003), and number of positive cores (OR 1.16, p = 0.004) were independently associated with APFs. Conclusions: AS stands as a safe option for low-risk patients, and most do not have APFs at surgery. Wider entry criteria are associated with pT3 and R1. The prognostic implications remain uncertain.

The clinical relative biological effectiveness and prostate-specific antigen kinetics of carbon-ion radiotherapy in low-risk prostate cancer.

To evaluate the clinical relative biological effectiveness (RBE) of carbon-ion radiotherapy (C-ion RT) for prostate cancer. The records of 262 patients with low-risk prostate cancer (median age, 65 [47-80] years) treated with C-ion RT at QST Hospital, National Institutes for Quantum Science and Technology in Japan during 2000-2018 were reviewed retrospectively. Four different protocol outcomes and prostate-specific antigen (PSA) responses were evaluated. The median follow-up was 8.4 years. The Kaplan-Meier method was used to estimate the biochemical or clinical failure-free rate (BCFFR). Clinical RBE was calculated using the tumor control probability model. The 5-, 7-, and 10-year BCFFRs were 91.7%, 83.8%, and 73.2%, respectively. The 10-year BCFFRs of patients who received C-ion RT at 66 Gy (RBE) in 20 fractions, 63 Gy (RBE) in 20 fractions, and 57.6Gy (RBE) in 16 fractions were 81.4%, 70.9%, and 68.9%, respectively. The PSA level and density during follow-up were better in the patients treated with the lower fraction size. A higher PSA nadir and shorter time to PSA nadir were risk factors for biochemical or clinical failure by multivariate Cox regression. The tumor control probability analysis showed that the estimated clinical RBE values to achieve an 80% BCFFR at 10 years for 20, 16, and 12 fractions were 2.19 (2.18-2.24), 2.16 (2.14-2.23), and 2.12 (2.09-2.21), respectively. Using clinical data from low-risk prostate cancer patients, we showed the clinical RBE of C-ion RT decreased with increasing dose per fraction.

Adverse upgrading and/or upstaging in contemporary low-risk prostate cancer patients

BackgroundUpgrading and/or upstaging in low-risk prostate cancer (PCa) patients may represent an indication for active treatment instead of active surveillance (AS). We addressed contemporary upgrading and/or upstaging rates in a large population based-cohort of low-risk PCa patients.Materials and methodsWhitin the SEER database (2010–2015), NCCN low-risk PCa patients were identified across management modalities: radical prostatectomy (RP), radiotherapy (RT) and non-local treatment (NLT). In RP patients, upgrading and/or upstaging rates were assessed in logistic regression models.ResultsOverall, of 27,901 low-risk PCa patients, 38% underwent RP vs 28% RT vs 34% NLT. RP patients were the youngest and harbored the highest percentage of positive cores and a higher rate of cT2a than NLT. At RP, 46.2% were upgraded to GGG ≥ 2, 6.0% to GGG ≥ 3 and 10.5% harbored nonorgan-confined stage (NOC, pT3-4 or pN1). Of NOC patients, 1.6% harbored GGG ≥ 3, 6.3% harbored GGG2 and 2.6% harbored GGG1. Of pT2 patients, 4.4% harbored GGG ≥ 3, 33.9% harbored GGG2 and 51.3% harbored GGG1. Age, PSA, percentage of positive cores and number of positive cores independently predicted the presence of NOC and/or GGG ≥ 3, but with low accuracy (63.9%).ConclusionsIn low-risk PCa, critical changes between tumor grade and stage at biopsy vs RP may be expected in very few patients: NOC with GGG ≥ 3 in 1.6% and NOC with GGG2 in 6.3%. Other patients with upgrading and/or upstaging combinations will invariably harbor either pT2 or GGG1 that far less critically affect PCa prognosis.

Abstract 1961: Discovery and validation of prostate cancer biomarkers of biochemical recurrence in low-risk prostate cancer patients

Abstract Introduction: Prostate cancer (CaP) is predominantly indolent disease with a small fraction of patients undergoing metastatic progression. Therefore, it is critical to identify prognostic markers for the early detection of an aggressive subtype. We hypothesized that tissue specimens from early-stage, low risk CaP may harbor predictive prognostic signatures for disease progression after radical prostatectomy. Previously, we had systematically evaluated and optimized the NanoString platform for CaP gene expression analysis in formalin fixed paraffin embedded (FFPE) whole mounted prostate specimens. The goal of the study is to validate the CPDR findings on the differential mRNA expression of candidate markers from patients with BCR (biochemical recurrence) and non-BCR in an independent cohort. Methods: This is a retrospective case cohort study based on 78 tumor-normal paired (N=156) archived whole mounted FFPE prostate samples received from biobank at UTHSCSA. We performed an optimized NanoString analysis of 203-CaP probe set to evaluate the association of markers with BCR outcome in a racially diverse patient population comprising of 21.6% AA and 78.38% CA men. The cohort comprised of 28 patients with BCR, and 50 patients with no BCR (based on a minimum of 5 years of follow-up). ERG gene expression was validated by immunohistochemistry (IHC) assay using CPDR ERG-MAb (9FY). Normalized nCounter gene expression data was analyzed using the NanoString nSolver (v 4.0) platform. Fisher exact and Wilcoxon-Mann-Whitney tests were used for categorical and continuous variables respectively. Results: We found 96.1% (73/76) concordance between ERG IHC and NanoString datasets, which provides strong QC and validation for NanoString data. ERG positive tumors had strong expression of both TMPRSS2-ERG fusion and several other ERG splice forms. Additionally, the prostate epithelial cell markers PSA, MSMB and PAP had the highest signals in all samples reflecting the prostate epithelial origin of the specimens. Differential gene expression analysis showed that a total of 37 genes were found to be significantly (P adj &amp;lt;0.05) different across tumors and normal. Established CaP genes like AMACR, PCA3, OR51E2, ERG, HOXC6, DLX1, CACNA1D and PSGR were most highly over-expressed in tumors compared to matched normal while GSTP1, CAV1, PAP and MSMB were significantly downregulated in tumors compared to adjacent normal prostate epithelia. Race stratified analysis in this randomly selected patient cohort showed that AA men were found to be significantly younger (median age: 56 years AA vs. 63 years CA; p 0.01) and had higher frequency of BCR events (p 0.004) than CA men. Data analysis for disease outcome across AA and CA men is ongoing. Conclusions: We confirmed that NanoString approach is useful for evaluation of prognostic biomarker candidates in prostate cancer using FFPE specimens. Citation Format: Indu Kohaar, Kaitlyn Bejar, Denise Young, Yingjie Song, Jiji Jiang, Jacob Kagan, Sudhir Srivastava, Javier Hernandez, Gregory Chesnut, Isabell A. Sesterhenn, Robin J. Leach, Gyorgy Petrovics. Discovery and validation of prostate cancer biomarkers of biochemical recurrence in low-risk prostate cancer patients [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 1961.

PD17-06 ACTIVE SURVEILLANCE DISCONTINUATION AMONG LOW-RISK PROSTATE CANCER PATIENTS: RESULTS FROM A LARGE NATIONAL DATABASE

You have accessJournal of UrologyCME1 May 2022PD17-06 ACTIVE SURVEILLANCE DISCONTINUATION AMONG LOW-RISK PROSTATE CANCER PATIENTS: RESULTS FROM A LARGE NATIONAL DATABASE Rashid Sayyid, Laurence Klotz, John Benton, Martha Terris, Christopher Wallis, and Zachary Klaassen Rashid SayyidRashid Sayyid More articles by this author , Laurence KlotzLaurence Klotz More articles by this author , John BentonJohn Benton More articles by this author , Martha TerrisMartha Terris More articles by this author , Christopher WallisChristopher Wallis More articles by this author , and Zachary KlaassenZachary Klaassen More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002555.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: A substantial proportion of prostate cancer (PCa) patients on active surveillance (AS) undergo definitive treatment within ten years of diagnosis. Patient factors influencing decision to opt for definitive therapy, and, specifically, choice of radical prostatectomy (RP) versus radiation therapy (XRT) remain unclear. METHODS: The Surveillance, Epidemiology, and End Results (SEER) Prostate with Watchful Waiting database was used to identify patients diagnosed with NCCN low-risk PCa between 2010 and 2015, managed with AS for at least one year following diagnosis. We sought to determine sociodemographic and oncologic predictors both of undergoing definitive intervention regardless of modality and of RP versus XRT, using multivariable logistic regression analysis. RESULTS: The study cohort included 32,874 men. 21,255 (64.7%) patients underwent delayed treatment, with 3,751 (17.6%) and 17,463 (82.4%) opting for RP and XRT, respectively. Median patient age was 64.0 years, 5,353 (16.3%) were African-American, and median PSA was 5.3 ng/ml. In addition to higher clinical stage, PSA at diagnosis and percent core involvement, multiple sociodemographic factors were associated with increased odds of receiving intervention on multivariable analysis: older age at diagnosis (odds ratio [OR] 1.33, p=0.007), diagnosis in the Southeast (OR 1.26, p <0.001) or Midwest (OR 1.22, p=0.021), and higher socioeconomic status (SES) (OR 1.67, p<0.001). Men who were uninsured (OR 0.34, p <0.001), had Medicaid (OR 0.82, p=0.024), or were not married (OR 0.85, p <0.001) were less likely to undergo definitive treatment.Sociodemographic factors predicting decreased odds of choosing RP (i.e. higher odds of receiving XRT) amongst patients opting for delayed treatment included: older age at diagnosis (OR 0.038,p<0.001), African American race (OR 0.71, p=0.018), unmarried status (OR 0.53, p<0.001), and higher SES (highest vs. lowest OR 0.65, p=0.001). CONCLUSIONS: The majority of low-risk PCa patients initially managed with AS underwent delayed treatment, with decision for discontinuation of AS and choice of RP versus XRT, in those who opt for definitive intervention, significantly associated with multiple sociodemographic and oncologic variables. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e338 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rashid Sayyid More articles by this author Laurence Klotz More articles by this author John Benton More articles by this author Martha Terris More articles by this author Christopher Wallis More articles by this author Zachary Klaassen More articles by this author Expand All Advertisement PDF DownloadLoading ...

Substantial Gleason reclassification in Black men with national comprehensive cancer network low-risk prostate cancer - A propensity score analysis.

Emerging evidence suggests that a subset of Black men with National Comprehensive Cancer Network (NCCN) low-risk prostate cancer (PCa) may harbor high volume and genomically aggressive disease. However, limited, and ambiguous research exist to evaluate the risk of extreme Gleason reclassification in Black men with low-risk PCa. This retrospective cohort study included 45,674 low-risk PCa patients who underwent prostatectomy and were not on active surveillance, from National Cancer Database (NCDB). A propensity score matched-pair design was employed, and the final cohort was limited to 1:1 matched 12,340 patients. Gleason score reclassification was used as primary endpoint. As such, any migration to pathologic Gleason score ≥7(3 + 4) was identified as overall, whereas migration to ≥7(4 + 3) was defined as extreme reclassification. A conditional Poisson regression model was used to estimate the risk of reclassification. Whereas spline model was used to estimate the impact of increasing time to treatment as a non-linear function on Gleason reclassification between race group. Upon matching there were no differences in the baseline characteristics between race groups. In a matched cohort, higher proportion of low-risk Black men (6.6%) reported extreme reclassification to pathologic Gleason score than White men (5.0%), p < 0.001. In a conditional Poisson regression model adjusted for time to treatment, the risk of overall (RR = 1.09, 95% CI, 1.05-1.13, p < 0.001) and extreme (RR = 1.30, 95% CI, 1.12-1.50, p = 0.004) reclassification was significantly higher in Black men as compared to their White counterpart. In spline model, the probability of Gleason reclassification in Black men was elevated with increasing time to treatment, especially after 180 days (53% vs. 43% between Black and White men). Risk of Gleason score reclassification is disparately elevated in Black men with low-risk PCa. Furthermore, time to treatment can non-linearly impact Gleason reclassification in Black men.

May Outcomes of Robotic Radical Prostatectomy Performed After an Initial Surveillance Strategy Differ from Those from Immediate Surgery? A Propensity Score-Matched Analysis on 362 Patients Undergoing Surgery at a Referral Center.

Introduction: Active surveillance (AS) is a treatment strategy for low-risk prostate cancer (PCa) patients, with extended indication to some intermediate-risk PCa. However, active treatment is necessary in case of disease progression and robotic radical prostatectomy (RALP) is one of the treatment modalities. The aim of the study is to compare outcomes of a delayed RALP after an initial heterogeneous surveillance strategy with those of immediate RALP in a single referral center. Methods: Data from patients who underwent RALP after initial assumed "active surveillance" (referred from different institutions and backgrounds) were compared to those of patients who underwent an immediate RALP after propensity score (PS) matching. The PS analysis was performed matching ISUP score at the time of entering surveillance with ISUP at RALP for the control group; other matching covariates at the time of surgery were considered (including age, prostate-specific antigen, body mass index, prostate size, cT, pre-op Sexual Health Inventory for Men, etc.). Perioperative, functional, and oncological outcomes were compared between groups. Results: Three hundred sixty-two RALP patients were included (181 after surveillance and 181 immediate RALP). Patients after surveillance had a worse pT and ISUP score (p < 0.001); LVI and EPE were higher in the surveilled group (13% vs. 5%, p = 0.001; 38% vs. 22%, p = 0.001), without significant difference in positive surgical margin. At a median follow-up of 24 months, the risk of biochemical recurrence (BCR) was significantly higher for delayed RALP (hazard ratio: 4.0; 95% confidence interval: 1.4-12; p = 0.013), whereas potency and continence rate did not differ significantly. Conclusions: At a referral center receiving patients from diverse backgrounds, outcomes of RALP after heterogeneous surveillance strategies are variable and less predictable, maybe attributable to different protocols and surgical planning. The higher BCR rate in a high-risk surveilled cohort may suggest an increased burden of cancer-related care for RALP patients after surveillance.

The Impact of Visible Tumor (PI-RADS ≥ 3) on Upgrading and Adverse Pathology at Radical Prostatectomy in Low Risk Prostate Cancer Patients: A Biopsy Core Based Analysis.

The objective of this study was to investigate the impact of the characteristics of a single visible tumor (Prostate Imaging-Reporting and Data System [PI-RADS]≥3) on upgrading and adverse pathology at radical prostatectomy (RP) in biopsy naïve low risk prostate cancer (PCa) patients. We retrospectively reviewed 64 biopsy naïve patients from 3 different referral centers between 2018 and 2020 with a PSA<10, cT1c disease, a single PI-RADS≥ 3 index lesion in multiparametric-MRI (mp-MRI), all bearing a GG 1 tumor sampled software fusion biopsy, who underwent RP. Preoperative clinical variables including the localization, number and tumor burden of positive cores for each PI-RADS category were related to upgrading and adverse pathology (GG>2 and/or pT3 and/or lymph node positive disease) at RP. Overall 37 patients (57.8%) were upgraded with a significant difference of upgrading in PI-RADS3 (30.0%) versus PI-RADS 4 (67.6%) (P=.007) and PI-RADS 4-5 (70.5%) lesions (P=.002). Thirty-three of 37 GG1 tumors were upgraded to GG2, while 6 of these 33 (18.2%) had adverse pathology as well. Overall 9 patients (14.1%) had adverse pathology at RP all harboring PI-RADS4-5 lesions. The number of positive cores differed significantly between the upgraded and nonupgraded patients. Adverse pathology group had significantly higher tumor volume at RP. PI-RADS4-5 lesions are the independent predictors of upgrading and adverse pathology in low risk PCa with visible tumors. Upgrading and adverse pathology were closely related to the number of positive combined cores reflecting the role of tumor volume. This should be kept in mind in shared decision making of an individual patient with low risk disease and a visible tumor.

Low serum total testosterone level as a predictor of upgrading in low-risk prostate cancer patients after radical prostatectomy: A systematic review and meta-analysis.

PurposeTo investigated the association between serum total testosterone and Gleason score upgrading of low-risk prostate cancer after radical prostatectomy (RP).Materials and MethodsMedline, Web of Science, Embase, and Cochrane Library databases were searched to identify eligible studies published before October 2021. Multivariate adjusted odds ratios (ORs) and associated 95% confidence intervals (CIs) were calculated using random or fixed effects models.ResultsFive studies comprising 1,203 low-risk prostate cancer patients were included. The results showed that low serum total testosterone (<300 ng/dL) is associated with a high rate of Gleason score upgrading after RP (OR, 2.3; 95% CI, 1.38–3.83; p<0.001; I2, 92.2%). Notably, sensitivity and meta-regression analyses further strengthen the reliability of our results.ConclusionsOur results support the idea that low serum total testosterone is associated with a high rate of Gleason score upgrading in prostate cancer patients after RP. It is beneficial for urologist to ensure close monitoring of prostate-specific antigen levels and imaging examination when choosing non-RP treatment for low-risk prostate cancer patients.

Utilization of IMRT and Brachytherapy for Low-Risk and Intermediate-Risk Prostate Cancer Patients: Analysis of the RealWorld Scenario

Purpose: Two main techniques in radiation therapy (RT) for the treatment of low-risk and intermediate-risk prostate cancer (PCa) are intensity-modulated radiation therapy (IMRT) and brachytherapy (BT). In this study, the pattern of utilization of IMRT, low dose-rate (LDR) BT, and high dose-rate (HDR) BT has been evaluated using a large hospital based registry database. Methods: We analyzed a very large data set of N0, M0, non-surgical, stage T1-T2c prostate cancer patients diagnosed between 2004 and 2015 from the National Cancer Database (NCDB). Based on the RT techniques used, we considered three groups of patients: (1) IMRT (n=61,159; 48.4%) who received an initial as well as a boost treatment with the IMRT, (2) BT LDR (n=43,293; 34.3%), and (3) BT HDR (n=21,938; 17.3%). A total dose of 70-81Gy for IMRT was considered. For brachytherapy, LDR and HDR or unspecified brachytherapy was considered as monotherapy. Patients were stratified according to the National Comprehensive Cancer Network (NCCN) guidelines into: low-risk [clinical stage T1-T2a, Gleason Score (GS) of ≤ 6 (Grade Group 1), and Prostate-specific antigen (PSA) of &lt; 10 ng/mL] and intermediate-risk [clinical stage T2b-T2c, GS of 7 (Grade Groups 2 and 3), and PSA of 10-20 ng/mL]. OS probability was determined using the Kaplan-Meier estimator. Propensityscore matched (PSM) analysis was performed for each risk group (low and intermediate) for the three research treatment modalities (IMRT, BT LDR, and BT HDR). IBM SPSS software was used for statistical analysis; p-value &lt;0.05 was considered statistically significant. Results: There has been a relative increase in IMRT usage for the treatment of both low-risk (29% to 53%) and intermediaterisk (53% to 77%) PCa patients from 2004 to 2015. Observed comparable median OS in low-risk and intermediate-risk patients in these three modalities IMRT (74.8/63.4 mo.), LDR (77.7/65.7 mo.) and HDR (83.5/72.1 mo.). Conclusion: The pattern of utilization of RT modality seems inclined toward increased use of IMRT over brachytherapy (59% vs. 41%) for both the low-risk and intermediate-risk PCa patients. Over the years, use of IMRT increased more in low-risk patient group than in intermediate-risk group.