Primary Gleason Score Research Articles

Prognostic model for second progression-free survival and overall survival in patients with high-risk metastatic hormone-sensitive prostate cancer treated with abiraterone acetate and androgen deprivation therapy.

To develop and validate a prognostic risk model for high-risk metastatic hormone-sensitive prostate cancer (mHSPC) patients treated with upfront abiraterone acetate (ABI). This retrospective multicenter study involved 233 high-risk mHSPC patients who received upfront ABI, developed by three academic centers. The model was externally validated with an independent cohort of 282 patients. To identify independent prognostic factors for second progression-free survival (PFS2) and develop the best-fitted model, Cox proportional hazards regression, followed by the Akaike information criterion, was used. Patients were categorized into three groups based on their risk scores. PFS2 and overall survival (OS) were evaluated according to the risk groups in the discovery and validation cohorts. The median age was 72 (range 51-89) years, with a median follow-up duration of 27 months. Independent factors linked to PFS2 included an Eastern Cooperative Oncology Group performance status ≥2, a primary Gleason score of 5, an extent of disease score of ≥3 or liver metastasis, and lactate dehydrogenase >220 U/L. Median PFS2 for favorable-, intermediate-, and poor-risk groups were not reached, 43 months, and 16 months, respectively. The median OS was 29 months in the poor-risk group, whereas it was not reached in the favorable- and intermediate-risk groups. The 2-year OS rates in the favorable-, intermediate- and poor-risk groups were 94.5%, 80.1%, and 60.3%, respectively. The validation cohort confirmed the risk model's relationship with PFS2 and OS. The median PFS2 and OS in the high-risk group were 21 months and 32 months, respectively. Our prognostic model, including five clinical factors, is useful for patient care and treatment selection in high-risk mHSPC patients treated with ADT plus ABI. The developed model could provide more accurate information, guide treatment decisions, or classify patients in future clinical trials.

Treatment modalities and survival outcomes in prostate cancer parenchymal brain metastasis.

Prostate cancer (PCa) parenchymal brain metastases are uncommon and troubling observations in the course of the disease. Our study aims to evaluate the prevalence of brain metastases among PCa patients while reporting various therapeutic modalities, clinical features, and oncological outcomes. We retrospectively identified 34 patients with parenchymal brain metastasis out of 4575 patients using a prospectively maintained database that contains clinicopathologic characteristics of PCa patients between January 2012 and December 2021. Based on the three treatment modalities used, the patients were divided into three groups: stereotactic radiosurgery (SRS), whole brain radiotherapy (WBRT), and systemic therapy alone. The Kaplan-Meier curve was used to calculate overall survival [OS] probability and the Cox proportional hazards regression model was used to compare between groups. At the time of brain metastasis diagnosis, the median age was 66 years, the median (interquartile range [IQR]) prostate-specific antigen (PSA) was 2.2 (0.1-26.6) ng/ml and the median (IQR) months from initial PCa diagnosis to brain metastasis development was 70.8 (27.6-100.9). The median (IQR) primary Gleason score was 8 (7-9) and over a median (IQR) follow-up time of 2.2 (1.2-16.5) months, 76.5% (n = 26) of the patients died. Thirteen (38.2%) patients had solitary lesion, whereas 21 (61.8%) had ≥2 lesions. The lesions were supratentorial in 19 (55.9%) patients, infratentorial in six (17.6%), and both sides in nine (26.5%). Among all 34 patients, 10 (29.4%) were treated with SRS, seven (20.6%) with WBRT, and 17 (50%) with systemic therapy alone. OS varied greatly between the three treatment modalities (log-rank test, p = 0.049). Those who were treated with SRS and WBRT had better OS compared with patients who were treated with systemic therapy alone (hazard ratio: 0.37, 95% confidence interval: 0.16-0.86, p = 0.022). In our single-institutional study, we confirmed that PCa brain metastasis is associated with poor survival outcomes and more advanced metastatic disease. Furthermore, we found that SRS and WBRT for brain metastasis in patients with recurrent PCa appear to be associated with improved OS as compared with systemic therapy alone and are likely secondary to selection bias.

Machine Learning and Explainable Artificial Intelligence to Predict Occult Pelvic Nodal Metastases in Prostate Cancer.

Determination of risk of occult pelvic lymph node involvement (LNI) in patients with cN0 prostate cancer is critical for determination of optimal treatment options. Though several nomograms exist, machine learning (ML) approaches might enable physicians to better assess individual risk by incorporating multiple clinical risk factors. Herein, we developed a ML model to predict occult LNI, and explained its composition using an explainable artificial intelligence (XAI) framework. Patients with cN0 prostate adenocarcinoma diagnosed from 2018-2020 were identified in the National Cancer Database. The query was limited to patients with known clinical staging and biopsy results who did not receive neoadjuvant therapy prior to pelvic nodal examination. Occult LNI was defined as pN1 disease based on surgical evaluation, with a minimum of 10 nodes examined. Five ML models were trained to predict LNI. Variables incorporated into the model were age, core biopsy results, Gleason scores, preoperative prostate specific antigen (PSA), and clinical T-stage. Model performance, measured using area under the receiver operator characteristic curve (AUC) on a holdout testing dataset, was compared to multivariable logistic regression. The best-performing model was explained using SHapley Additive exPlanation (SHAP) values. To permit more clinically-meaningful statistical interpretation, using a novel approach SHAP values were converted into odds ratios (OR), confidence intervals (CI), and p-values. A total of 23,131 patients met inclusion criteria; 2,676 (11.6%) had occult LNI. The Extreme Gradient Boosting model outperformed all other models with an AUC of 0.82 (95% CI: 0.78-0.86) compared to 0.80 (95% CI: 0.76-0.84) for logistic regression. Increasing PSA (OR: 1.031; p<0.001), number of positive biopsy cores (OR: 1.055; p<0.001), and percent positive biopsy cores (OR: 1.01; p<0.001) were all associated with increased risk of LNI. Based on observation of SHAP dependence plots, risk of LNI plateaued at PSA>20 ng/dL and >11 positive cores, while no plateau was observed for percent positive biopsy cores. Relative to T1c disease, patients with T3b were at highest risk of LNI (OR: 1.461; p = 0.003). Gleason score of 9 was associated with significant risk of LNI (Ref: Gleason 6; OR: 1.891; p<0.001). This was primarily driven by the primary Gleason score; primary Gleason 5 disease was associated with significant risk of LNI (Ref: Gleason 3; OR: 1.915; p<0.001) while a secondary Gleason score of 5 was the only grade with significant increased risk of LNI (Ref: Gleason 3; OR: 1.185; p = 0.004). Age and number of cores examined were not significant predictors of LNI. Our ML achieved improved performance relative to logistic regression at predicting occult LNI. XAI provided insight into the inner-working of the ML model. ML can be used to identify patients at risk for occult LNI and therefore inform clinical decision-making.

Development and validation of novel nomogram to identify the candidates for extended pelvic lymph node dissection for prostate cancer patients in the robotic era.

To determine candidates for extended pelvic lymph node dissection using a novel nomogram to assess the risk of lymph node invasion in Japanese prostate cancer patients in the robotic era. A total of 538 patients who underwent robot-assisted radical prostatectomy with extended pelvic lymph node dissection in three hospitals were retrospectively analyzed. Medical records were reviewed uniformly and the following data collected: prostate-specific antigen, age, clinical T stage, primary and secondary Gleason score at prostate biopsy, and percentage of positive core numbers. Finally, data from 434 patients were used for developing the nomogram and data from 104 patients were used for external validation. Lymph node invasion was detected in 47 (11%) and 16 (15%) patients in the development and validation set, respectively. Based on multivariate analysis, prostate-specific antigen, clinical T stage ≥3, primary Gleason score, grade group 5, and percentage of positive cores were selected as variables to incorporate into the nomogram. The area under the curve values were 0.781 for the internal and 0.908 for the external validation, respectively. The present nomogram can help urologists identify candidates for extended pelvic lymph node dissection concomitant with robot-assisted radical prostatectomy among patients with prostate cancer.

MP29-20 FACTORS ASSOCIATED WITH POOR SURVIVAL OUTCOMES IN PROSTATE CANCER (PCA) PATIENTS WITH RADIOGRAPHIC DISEASE PROGRESSION IN THE SETTING OF LOW PSA

You have accessJournal of UrologyCME1 Apr 2023MP29-20 FACTORS ASSOCIATED WITH POOR SURVIVAL OUTCOMES IN PROSTATE CANCER (PCA) PATIENTS WITH RADIOGRAPHIC DISEASE PROGRESSION IN THE SETTING OF LOW PSA Mohamed Ahmed, Jack Andrews, Ahmed Mahmoud, Matthew Lee, Elizabeth Bearrick, Daniel Childs, A. Tuba Kendi, Matthew Tollefson, Stephen Boorjian, R. Jeff Karnes, and Eugene Kwon Mohamed AhmedMohamed Ahmed More articles by this author , Jack AndrewsJack Andrews More articles by this author , Ahmed MahmoudAhmed Mahmoud More articles by this author , Matthew LeeMatthew Lee More articles by this author , Elizabeth BearrickElizabeth Bearrick More articles by this author , Daniel ChildsDaniel Childs More articles by this author , A. Tuba KendiA. Tuba Kendi More articles by this author , Matthew TollefsonMatthew Tollefson More articles by this author , Stephen BoorjianStephen Boorjian More articles by this author , R. Jeff KarnesR. Jeff Karnes More articles by this author , and Eugene KwonEugene Kwon More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003257.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Recent studies, including a post-hoc analysis of the ARCHES trial, highlight radiographic disease progression (rDP) occurring without concordant rise in prostate specific antigen (PSA). In a previous study by our group, we reported that almost 40% of patients on 2nd generation hormone therapy experience rDP with non-rising PSA and have poor survival outcomes. The current analysis more specifically focuses on the subgroup of patients with rDP occurring at low PSA (<0.5 ng/dL) and describes factors associated with poorer survival outcomes in this patient population. METHODS: In a single institution study, we reviewed the prospectively maintained Mayo Clinic C-11 Choline PET registry for patients treated between 2011 and 2021, who experienced rDP at low PSA (value < 0.5 ng/mL). Disease progression on C-11 choline PET was confirmed by either tissue biopsy or subsequent response to therapy. We investigated factors associated with poor cancer-specific survival outcomes in univariable and multivariable cox regression analyses. RESULTS: In total, 220 (16%) patients experiencing rDP at low PSA were identified. Median (IQR) age at rDP was 67.91 (61.10 – 73.87) yrs., median (IQR) primary Gleason score was 9 (7-9), and median (IQR) PSA was 0.17 (0 – 0.32) ng/ml. 75% of the patients (n=166) had CRPC disease status at time of rDP. Prior systemic treatments included 2nd generation HT in 18% (n= 40) and chemotherapy in 31% (n=70). Sites of rDP were divided into 7% local (n=16), 42% lymph nodes (n=91), 43% bone (n=95), and 8% visceral metastases (n=18). Over a median follow-up duration of 55 months, 46% of patients (n=100) reported death. Factors associated with poor survival outcomes are demonstrated in table-1 and include age at rDP, CRPC status, and disease location (P-value <0.05). CONCLUSIONS: We found that radiographic disease progression commonly occurs at low PSA (<0.5 ng/mL). CRPC-disease status and the development of visceral metastases are associated with particularly poor survival outcomes. To identify early progression, monitoring with imaging may be warranted, even in the patients with low PSA. Source of Funding: none © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e390 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mohamed Ahmed More articles by this author Jack Andrews More articles by this author Ahmed Mahmoud More articles by this author Matthew Lee More articles by this author Elizabeth Bearrick More articles by this author Daniel Childs More articles by this author A. Tuba Kendi More articles by this author Matthew Tollefson More articles by this author Stephen Boorjian More articles by this author R. Jeff Karnes More articles by this author Eugene Kwon More articles by this author Expand All Advertisement PDF downloadLoading ...

Factors associated with poor survival outcomes in patients with prostate cancer (PCa) with radiographic disease progression in the setting of low PSA.

60 Background: Recent studies, including a post-hoc analysis of the ARCHES trial, highlight radiographic disease progression (rDP) occurring without concordant rise in prostate specific antigen (PSA). In a previous study by our group, we reported that almost 40% of patients on 2nd generation hormone therapy experience rDP with non-rising PSA and have poor survival outcomes. The current analysis more specifically focuses on the subgroup of patients with rDP occurring at low PSA (&lt;0.5 ng/dL) and describes factors associated with poorer survival outcomes in this patient population. Methods: In a single institution study, we reviewed the prospectively maintained Mayo Clinic C-11 Choline PET registry for patients treated between 2011 and 2021, who experienced rDP at low PSA (value &lt; 0.5 ng/mL). Disease progression on C-11 choline PET was confirmed by either tissue biopsy or subsequent response to therapy. We investigated factors associated with poor cancer-specific survival outcomes in univariable and multivariable cox regression analyses. Results: In total, 220 (16%) patients experiencing rDP at low PSA were identified. Median (IQR) age at rDP was 67.91 (61.10 – 73.87) yrs., median (IQR) primary Gleason score was 9 (7-9), and median (IQR) PSA was 0.17 (0 – 0.32) ng/ml. 75% of the patients (n=166) had CRPC disease status at time of rDP. Prior systemic treatments included 2nd generation HT in 18% (n= 40) and chemotherapy in 31% (n=70). Sites of rDP were divided into 7% local (n=16), 42% lymph nodes (n=91), 43% bone (n=95), and 8% visceral metastases (n=18). Over a median follow-up duration of 55 months, 46% of patients (n=100) reported death. Factors associated with poor survival outcomes are demonstrated in the table and include age at rDP, CRPC status, and disease location (P-value &lt;0.05). Conclusions: We found that radiographic disease progression commonly occurs at low PSA (&lt;0.5 ng/mL). CRPC-disease status and the development of visceral metastases are associated with particularly poor survival outcomes. To identify early progression, monitoring with imaging may be warranted, even in the patients with low PSA. [Table: see text]

Prognostic value of C-11 choline PET/CT scan in patients with metastatic castration resistant prostate cancer (m-CRPC) undergoing treatment with radium-223.

59 Background: Radium-223 (Ra-223) has been approved for the treatment of metastatic castration resistant prostate cancer (mCRPC) with predominantly osseous metastases. PSA flare phenomenon with Ra-223 limits the use of PSA as a prognostic tool to predict treatment response. Currently, there is a lack of diagnostic tools to predict treatment response to Ra-223. Therefore, we sought to investigate the role of mid-treatment C-11 choline PET/CT scan in predicting overall response to Ra-223. Methods: In a single institute retrospective study, we identified 32 patients who were treated with a full course of 4-6 cycles of Ra-223 and were evaluated with both PSA and C-11 choline PET scan before treatment, at mid-treatment, and after a complete course of Ra-223 between 2013 – 2018. Ra-223 was used as salvage therapy for their predominant bone disease after failing chemotherapy and 2nd generation hormone therapy. Blind repeat radiographic evaluation of patients’ scans was performed by a radiologist specialized in nuclear radiology. Favorable response was defined by achieving partial response or stable disease on imaging, while unfavorable response was defined by showing progressive disease on imaging. Results: Mean age (±SD) at starting Radium223 was 67.6 (±7.1) years, median (IQR) primary Gleason score was 9 (8-9), and median (IQR) pretreatment PSA was 13.5 (5.4-39.6) ng/ml. 78% of the patients (n=25) completed 6 cycles of Ra-223, 15% of the patients (n=5) completed 5 cycles, and 6% (n=2) received only 4 cycles. At mid-treatment scanning, 25% of the patients (n=8) showed favorable response (Group A), while 75% of the patients (n=24) showed unfavorable response (B). After a complete course of treatment, 62.5% of patients (n=5) in Group (A) continued to show favorable response, while only 8.3% of patients (n=2) in Group (B) showed favorable response (p-value= 0.0023). Conclusions: Mid-treatment evaluation with C-11 choline PET/CT scan can predict overall response to Radium 223. Patients with progressive disease at mid-treatment evaluation are very likely not going to respond to further treatment. Further studies and clinical trials are warranted.

Effect of early PSA decline after starting second-generation hormone therapy in the post-docetaxel setting on cancer-specific survival in metastatic castrate-resistant prostate cancer.

189 Background: The objective of this study is to evaluate the prognostic value of early PSA decline following initiation of second-generation hormone therapy (2nd HT), namely abiraterone acetate or enzalutamide, in the post-chemotherapy setting in patients with metastatic castrate-resistant prostate cancer (mCRPC). Methods: We retrospectively identified 75 m-CRPC patients treated with 2nd HT following docetaxel failure (defined as PSA rise and radiographic progression). Patients were categorized into two groups based on first PSA within 3 months after initiation of therapy: PSA reduction ≥ 50% (Group A) and PSA reduction &lt; 50% (Group B). The primary endpoint was cancer-specific mortality and the secondary endpoint was radiographic progression free survival. Results: There were 75 patients (52 in group A, 23 in group B) in the analytic cohort. Baseline clinical and demographic characteristics, including median age, primary Gleason score risk group, median pre-treatment PSA, disease burden, site of metastases, and pre-treatment ECOG score were not statistically different between the two groups. PSA reduction ≥50% was significantly associated with decreased risk of radiographic disease progression (HR 0.41, 95%CI 0.21-0.80, p = 0.0113) as well as decreased risk of cancer-specific mortality (HR 0.29, 95%CI 0.09-0.87, p = 0.0325). Conclusions: PSA reduction ≥50% within 3 months of starting 2nd HT for patients with mCRPC who have failed first-line docetaxel is associated with significantly improved 3-year cancer-specific mortality and progression free survival. Our data supports the use of PSA as an early prognosticating marker for patient outcomes on this second line therapy. [Table: see text]

MP45-12 PTEN LOSS AND DIFFUSIVE KI67 PREDICT BIOCHEMICAL RECURRENCE OF LOCALIZED PROSTATE CANCER AFTER RADICAL PROSTATECTOMY: A VALIDATION COHORT STUDY

You have accessJournal of UrologyCME1 May 2022MP45-12 PTEN LOSS AND DIFFUSIVE KI67 PREDICT BIOCHEMICAL RECURRENCE OF LOCALIZED PROSTATE CANCER AFTER RADICAL PROSTATECTOMY: A VALIDATION COHORT STUDY Che Hsueh Yang, Yi Sheng Lin, Wei Chun Weng, Chin Heng Lu, Chung Hsiao Chin, Tang Yi Tsao, Chao Yu Hsu, Min Che Tung, and Yen Chuan Ou Che Hsueh YangChe Hsueh Yang More articles by this author , Yi Sheng LinYi Sheng Lin More articles by this author , Wei Chun WengWei Chun Weng More articles by this author , Chin Heng LuChin Heng Lu More articles by this author , Chung Hsiao ChinChung Hsiao Chin More articles by this author , Tang Yi TsaoTang Yi Tsao More articles by this author , Chao Yu HsuChao Yu Hsu More articles by this author , Min Che TungMin Che Tung More articles by this author , and Yen Chuan OuYen Chuan Ou More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002611.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Although Ki67 and PTEN emerge as promising markers of localized prostate cancer (PC) after radical prostatectomy (RP), they are still not recommended for routine risk assessments in guidelines. This study aims to validate their prognostic values in time-to- biochemical recurrence (BCR) of localized PC after RP. METHODS: Between 2015 and 2017, men of localized PC after robot-assisted RP were retrospectively reviewed. Their specimens were re-stained with immunohistochemical (IHC) markers of Ki67 and PTEN and were interpreted according to suggestions of International Society of Urological Pathology. Diffusive Ki67 was defined as 30% positivity (diffusive: Ki67+, non-diffusive: Ki67-) and PTEN was categorized into intact (PTEN +), heterogenous loss(PTEN-) and homogenous loss (PTEN 2-). Independent variables of Ki67 and PTEN were examined through univariable and multivariable Cox regression, and dependent variable was time-to-BCR. Other meaningful independent variables in univariable Cox regression would be incorporated into multivariable Cox regression analysis with Ki67 and PTEN. Kaplan Meier (KM) curve was applied to visualize and compare survival outcomes. RESULTS: A total of 215 men were reviewed with a mean surveillance of 66.85±6.62 months. Meaningful variables analyzed with Ki67 and PTEN in multivariable Cox regression were preoperative PSA, primary Gleason score, T stage, N stage, perineural invasion, angiolymphatic invasion,tumor percentage and positive surgical margins. In multivariable Cox regression of time-to-BCR, PTEN- (HR:1.95 (1.10-3.43)), PTEN 2- (HR:3.08 (1.78-5.35)) and Ki67+(HR:2.38 (1.47-3.83)) were significant factors. In KM curve, except for the comparison of Ki67-/PTEN 2- and Ki67+/PTEN+ (p=0.476), all subgroups comparisons were statistically significant (p<0.05). CONCLUSIONS: PTEN 2-, PTEN - and Ki67+ are all related to BCR of localized PC after RP. Judging from KM curve, Ki67+ and PTEN 2- are in higher risks developing BCR than PTEN -, and PTEN 2- is equivalent to Ki67+ in predicting BCR after RP. Source of Funding: Nothing to disclose © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e767 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Che Hsueh Yang More articles by this author Yi Sheng Lin More articles by this author Wei Chun Weng More articles by this author Chin Heng Lu More articles by this author Chung Hsiao Chin More articles by this author Tang Yi Tsao More articles by this author Chao Yu Hsu More articles by this author Min Che Tung More articles by this author Yen Chuan Ou More articles by this author Expand All Advertisement PDF DownloadLoading ...

18F-rhPSMA-7 PET for the Detection of Biochemical Recurrence of Prostate Cancer After Curative-Intent Radiation Therapy: A Bicentric Retrospective Study.

This bicentric, retrospective analysis investigated the efficacy of PET/CT with a novel theranostic prostate-specific membrane antigen (PSMA)--targeting ligand, 18F-rhPSMA-7, in patients with biochemical recurrence (BCR) of prostate cancer after curative-intent primary radiotherapy. Methods: Datasets from patients with BCR of prostate cancer after external-beam radiation therapy or brachytherapy who underwent 18F-rhPSMA-7 PET/CT at either Technical University Munich or Ludwig-Maximilians-University Munich were retrospectively reviewed by experienced nuclear medicine physicians and radiologists at both centers. The median injected activity was 299 MBq (range, 204-420 MBq), and the median uptake time was 77 min (range, 46-120 min). All lesions suggestive of recurrent prostate cancer were noted. Detection rates were correlated with patients' prostate-specific antigen (PSA) level, primary Gleason score, and prior use of androgen-deprivation therapy (ADT). Results: Ninety-seven patients were included (65 at Technical University Munich and 32 at Ludwig-Maximilians-University Munich). The median prescan PSA was 4.19 ng/mL (range, 0.1-159 ng/mL). The primary Gleason score was ≤6 in 19 patients, 7 in 25, ≥8 in 33, and unknown in 20. Thirty patients received ADT in the 6 mo preceding PET/CT. 18F-rhPSMA-7 identified lesions in 91 of 97 (94%) patients. Detection rates stratified by PSA were 88% (22/25), 97% (30/31), 90% (19/21), and 100% (20/20) for a PSA of <2, 2-<5, 5-<10, and ≥10 ng/mL, respectively. Detection rates in the subgroup of patients not meeting the Phoenix criteria for BCR were 80% (4/5), 90% (9/10), 100% (4/4), and 83% (5/6) for a PSA of <0.5, 0.5-<1, 1-<1.5, and 1.5-2 ng/mL, respectively. There were no significant differences in detection rates between patients with and without prior ADT (100% vs. 91%, P = 0.173) or patients with a Gleason score of ≤7 and a Gleason score of ≥8 (98% vs. 91%, P = 0.316).18F-rhPSMA-7 revealed local recurrence in 80% (78/97); pelvic lymph node metastases in 38% (37/97); retroperitoneal and supradiaphragmatic lymph node metastases in 9% (9/97) and 4% (4/97), respectively; bone metastases in 27% (26/97); and visceral metastases in 3% (3/97). In the subgroup of patients with a PSA of <2 ng/mL above nadir, local recurrence occurred in 76% (19/25) and pelvic lymph node metastases in 36% (9/25). Conclusion:18F-rhPSMA-7 PET/CT demonstrates high detection rates in prostate cancer patients with BCR after primary radiation therapy, even at low PSA values. Its diagnostic efficacy is comparable to published data for other PSMA ligands.

Evaluation of 18F-PSMA-1007 PET/CT in prostate cancer patients with biochemical recurrence after radical prostatectomy

PurposeProstate-specific membrane antigen (PSMA) ligands targeting has shown promising results in staging of prostate cancer (PCa). The aim of present study was to evaluate the value of 18F-PSMA-1007 PET/CT in PCa patients with biochemical recurrence. Methods71 patients with PCa after radical prostatectomy (RP) were included in the present study. Median prostate-specific antigen (PSA) level was 1.27 ng/mL (range 0.01–67.40 ng/mL, n = 69). All patients underwent whole-body PET/CT imaging after injection of 333±38 MBq 18F-PSMA-1007. The distribution of PSMA-positive lesions was assessed. The influence of PSA level, androgen deprivation therapy and primary Gleason score on PSMA-positive finding and uptake of 18F-PSMA-1007 were evaluated. Results56 (79%) patients showed at least one pathological finding on 18F-PSMA-1007 PET/CT. The rates of positive scans were 50%, 80%, 100%, 100% among patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and >2.0 ng/mL, respectively. The median Gleason score was 8 (range 7–10), and higher Gleason score (≤7 vs. ≥8) leads to higher detection rates (58.3% (14/24) vs. 88.9% (32/36), P = 0.006). The median SUVmax of positive findings in patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and >2.0 ng/mL were 4.51, 4.27, 11.50 and 14.08, respectively. The median SUVmax in patients with PSA level >2.0 ng/mL was significantly higher than that in patients with PSA ≤2.0 ng/mL (14.08 vs. 6.13, P<0.001). Conclusion18F-PSMA-1007 PET/CT demonstrated a high detection rate for patients with a raised PSA level after radical prostatectomy even in patients with extremely low PSA level (eg. PSA level ≤0.5 ng/mL), which was essential for further clinical management for PCa patients.

Impact of prostate biopsy secondary pathology review on radiotherapy management.

The Gleason scoring system is the most widely used method to assess prostate adenocarcinoma pathology however interobserver variability is significant. Gleason score, PSA level, and clinical stage comprise the NCCN risk stratification that guides treatment decision making. Given the importance of an accurate Gleason score and wide interobserver variability, referral centers routinely review outside pathology at the time of consultation. We sought to address the impact a secondary pathology review had on radiation therapy treatment recommendations in men with prostate cancer at our institution. We retrospectively collected patient data on 342 patients seen at our institution from January 2012 to December 2018. Clinicopathologic data were used to subdivide patients into risk groups and available treatment options per NCCN criteria. Cases reviewed by our genitourinary pathologist (GUP) were compared with reports from outside pathologists. Inter-rater reliability between pathologists was assessed with weighted Cohen's kappa statistic and agreement of treatment options was determined by McNemar's exact tests. GUP scored more cores positive in 16.47% of cases on secondary review. Primary Gleason score was changed in 12.28% of patients and secondary score in 26.02% of cases. Total Gleason score was different in 29.24% of cases, 19.01% were downgraded and 10.23% upgraded. The weighted kappa statistic was 0.759 (95% confidence interval [CI]: 0.711, 0.807). 18.77% of patients were assigned to a different NCCN risk group following secondary review. The weighted kappa statistic comparing NCCN risk stratification was 0.802 (95% CI: 0.754, 0.850). Secondary review influenced radiation therapy recommendations pertaining to brachytherapy boost and androgen deprivation therapy in men with high risk disease (χ2 = 5.33, p = 0.0386; χ2 = 8.05, p = 0.0072, respectively). Kappa statistic was found to be highest when GUP assessed high-risk disease versus all other categories (κ = 0.823, 95% CI: 0.750, 0.895). We found nearly one in five men (18.7%) was assigned a different NCCN risk group and thus offered potentially different treatment options after a secondary pathology review at our institution. Given the inherent nature of prostate cancer and lung disease-specific survival associated with modern therapies, our study demonstrates the importance of a secondary pathology review and its potential impact on radiation therapy recommendations.

Exploration on Gleason score variation trend of patients with prostate carcinoma from 1996 to 2019: a retrospective single center study.

Gleason score (GS) is one of the stronger prognostic factors and is integral to the management of prostate carcinoma. Subsequent modifications, recommended by the International Society of Urological Pathology in 2005 and 2014, enabled accurate prediction of prognosis. The present study investigated GS variation trend of patients with prostate carcinoma from 1996 to 2019 and offered an overview of GS changes with age, specimen type, histopathological type and serum prostate specific antigen (PSA). One thousand three hundred and seventy-six patients, admitted to Peking University People's Hospital in 1996 to 2019, were divided into 1996 to 2006, 2007 to 2015 and 2016 to 2019 groups. Data, including demographic characteristics, GS, primary and secondary grade and percentage of primary and secondary grade of each group, were collected and analyzed. The population distribution and average of GS was evaluated, after segmented and stratified by age, type of specimen, histopathological type and PSA. The average of age and PSA of each cohort had no obvious change. The average of total GS fluctuated among three cohorts with statistically significant differences. The distribution of age and PSA did not differ among cohorts. The distribution of total and primary GS shifted, with more patients detected as total GS higher than 6 (86.1%), and more primary grade higher than 3 (56.7%) in 2016-2019. After segmented and stratified by age, specimen type, histological type and PSA, the population percentage of GS over 6 was significantly higher in 2016-2019 than 1996-2006 and 2007-2015 in patients aged younger than 80 years (age <60, 89.6%, age 60-69, 82.0%, age 70-79, 87.7%). Patients, aged below 80 years in 2016-2019, were detected with higher total GS. In the present study, GS in patients with prostate carcinoma showed a upward trend. Primary grade, age, serum PSA and specimen type were the main reasons for GS changing while secondary grade, tissue types and diagnostic criteria influenced less.

Surgical Delay and Pathological Outcomes for Clinically Localized High-Risk Prostate Cancer

There is a lack of data evaluating the association of surgical delay time (SDT) with outcomes in patients with localized, high-risk prostate cancer. To investigate the association of SDT of radical prostatectomy and final pathological and survival outcomes. This cohort study used data from the US National Cancer Database (NCDB) and identified all patients with clinically localized (cT1-2cN0cM0) high-risk prostate adenocarcinoma diagnosed between 2006 and 2016 who underwent radical prostatectomy. Data analyses were performed from April 1 to April 12, 2020. SDT was defined as the number of days between the initial cancer diagnosis and radical prostatectomy. SDT was categorized into 5 groups: 31 to 60, 61 to 90, 91 to 120, 121 to 150, and 151 to 180 days. The primary outcomes were predetermined as adverse pathological outcomes after radical prostatectomy, including pT3-T4 disease, pN-positive disease, and positive surgical margin. The adverse pathological score (APS) was defined as an accumulated score of the 3 outcomes (0-3). An APS of 2 or higher was considered a separate outcome to capture cases with more aggressive pathological features. The secondary outcome was overall survival. Of the 32 184 patients included in the study, the median (interquartile range) age was 64 (59-68) years, and 25 548 (79.4%) were non-Hispanic White. Compared with an SDT of 31 to 60 days, longer SDTs were not associated with higher risks of having any adverse pathological outcomes (odds ratio [OR], 0.95; 95% CI, 0.80-1.12; P = .53), pT3-T4 disease (OR, 0.99; 95% CI, 0.83-1.17; P = .87), pN-positive disease (OR, 0.79; 95% CI, 0.59-1.06; P = .12), positive surgical margin (OR, 0.88; 95% CI, 0.74-1.05; P = .17), or APS greater than or equal to 2 (OR, 0.90; 95% CI, 0.74-1.05; P = .17). Longer SDT was also not associated with worse overall survival (for SDT of 151-180 days, hazard ratio, 1.12; 95% CI, 0.79-1.59, P = .53). Subgroup analyses performed for patients with very high-risk disease (primary Gleason score 5) and sensitivity analyses with SDT considered as a continuous variable yielded similar results. In this cohort study of patients who underwent radical prostatectomy within 180 days of diagnosis for high-risk prostate cancer, radical prostatectomy for high-risk prostate cancer could be safely delayed up to 6 months after diagnosis.

Role of metastases-directed therapy (MDT) in the management of solitary metastatic prostate cancer.

143 Background: Systemic treatment in the management of metastatic prostate cancer is inevitable. However, there is a growing interest in metastases-directed therapy (MDT). We sought to investigate the efficacy of MDT in treating patients with solitary metastatic prostate cancer and hence, delaying initiation of systemic treatment (i.e., Androgen deprivation therapy or chemotherapy). Methods: We retrospectively identified 61 patients treated with targeted therapy in the form of surgery (n = 30), stereotactic body radiation therapy (SBRT) (n = 25), or cryotherapy (n = 7) for their solitary metastases prostate cancer. Complete response was defined by achieving a PSA value of ≤0.2 ng/ml plus resolution of the solitary metastatic lesion on C-11 choline PET choline scan, while incomplete response was defined by a residual PSA of &gt; 0.2 ng/ml and/or radiographic evidence of disease following metastases-targeted therapy. Results: Mean (±SD) age was 68.4 (±7.8) yrs., median (IQR) primary Gleason Score was 7 (7-9) and median (IQR) pre-MDT PSA was 2 (1.3-3.8) ng/ml. Median (IQR) time from primary treatment of the prostate to MDT was 5.1 (2.7-10.1) years. None of the patients were on hormone therapy at the time of presentation with solitary metastases prostate cancer. 30 patients had bone metastases, 29 patients had lymph node metastases, 1 patient had soft tissue metastasis (pelvic metastatic mass), and another patient had visceral metastasis (to the lung). 42% of the patients (n = 26) achieved complete response to targeted therapy. Median time to initiation of 2nd line systemic treatment following MDT was 17.8 months for the complete responders versus 9.3 months for incomplete responders. 11% of the patients (n = 7) did not require 2nd line therapy after their MDT for a mean (±SD) time of 56.9 (±22.5) months. Conclusions: The use of targeted therapy in the management of patients with solitary metastatic disease or low-volume metastatic disease can provide comparable outcomes to those of systemic treatment. Further studies are warranted.

Non-rising PSA disease progression on C-11 choline PET/CT imaging in patients receiving second generation hormone therapies (2nd-HT).

144 Background: Despite having well-recognized limitations, urologists often rely on serial PSA testing as a marker for treatment response or disease progression. To determine if PSA was indeed a reliable marker for treatment response or disease progression, we compared PSA levels against C-11 choline PET/CT in the evaluation of patients with advanced prostate cancer treated with second generation hormonal therapy (2nd-HT). Methods: We retrospectively identified 239 patients who were undergoing treatment with 2nd-HT (enzalutamide or abiraterone) for advanced prostate cancer. While on treatment, patients underwent serial PSA testing and C-11 choline PET/ CTs every 3 – 6 months. Paradoxical response was defined as increasing blood pool-corrected SUVmax of known choline-avid lesions and/or identification of new choline-avid lesions, despite stable or down-trending PSA. Results: Median (IQR) age was 70.4(64.3 – 75.7) years and median (IQR) primary Gleason Score was 8 (7 – 9). In our study, 19% of patients (n = 46/239) who were receiving 2nd-HT exhibited paradoxical response. Median (IQR) PSA and corrected SUVmax at baseline evaluation were 1.3 ng/mL (0.3 – 12.8 ng/mL) and 3.5 (1.8 – 5.8), respectively. Median (IQR) PSA and corrected SUVmax at the time of paradoxical response were 0.4 ng/mL (0.1 – 5.4 ng/mL) and 4.5 (2.8 – 6.8), respectively. The median duration of 2nd-HT treatment prior to detection of paradoxical response was 4.8 months (2.9 – 10.1 months). No significant difference was noted between patients receiving enzalutamide versus abiraterone (p = 0.35). Independent predictors of paradoxical response were prior primary systemic treatment (i.e. hormonal/chemo-hormonal therapy versus local therapy) and patient’s age at time of 2nd-HT initiation on univariate and multivariate analysis. Conclusions: Our retrospective review demonstrated prostate cancer disease progression discordant with PSA down-trending in 19% of patients receiving 2nd-HT. We conclude that in this subset of patients with advanced prostate cancer, PSA may not be a reliable marker of treatment response of disease progression, and routine radiographic evaluation in these patients is warranted.

18F-rhPSMA-7 PET for the Detection of Biochemical Recurrence of Prostate Cancer After Radical Prostatectomy.

18F-labeled prostate-specific membrane antigen (PSMA) PET tracers are increasingly used in preference to 68Ga-PSMA-11 for restaging biochemical recurrence (BCR) of prostate cancer. They are associated with longer half-lives, larger-scale production, and lower positron range than their 68Ga-labeled counterparts. Here, we describe the efficacy of an 18F-labeled radiohybrid PSMA, rhPSMA-7, a novel theranostic PSMA-targeting agent for imaging BCR of prostate cancer. Methods: Datasets from 261 consecutive patients with noncastrate BCR after radical prostatectomy who underwent 18F-rhPSMA-7 PET/CT at our institution between June 2017 and March 2018 were reviewed retrospectively. All lesions suspected of being recurrent prostate cancer were recorded. The detection rate for sites of presumed recurrence was correlated with patients' prostate-specific antigen (PSA) level, primary Gleason score, and prior therapy (androgen deprivation therapy and external-beam radiation therapy). Results: The 261 patients had a median PSA level of 0.96 ng/mL (range, 0.01-400 ng/mL). The median injected activity of 18F-rhPSMA-7 was 336 MBq, with a median uptake time of 76 min. In total, 211 patients (81%) showed pathologic findings on 18F-rhPSMA-7 PET/CT. The detection rates were 71% (42/59), 86% (44/51), 86% (42/49), and 95% (76/80) at PSA levels of 0.2 to <0.5 ng/mL, 0.5 to <1 ng/mL, 1 to <2 ng/mL, and ≥2 ng/mL, respectively. In 32% patients (7/22) with a PSA of less than 0.2 ng/mL, suggestive lesions were present. 18F-rhPSMA-7 PET/CT revealed local recurrence in 43% of patients (113). Lymph node metastases were present in the pelvis in 42% of patients (110), in the retroperitoneum in 17% (45), and in a supradiaphragmatic location in 8.0% (21). Bone and visceral metastases were detected in 21% (54) and 3.8% (10), respectively. Detection efficacy was not influenced by prior external-beam radiation therapy (79.1% vs. 82.1%, P = 0.55), androgen deprivation therapy within the 6 mo preceding imaging (80.6% vs. 80.9%, P = 0.54), or primary Gleason score (77.9% for ≤7 vs. 82.6% for ≥8, P = 0.38). Conclusion:18F-rhPSMA-7 PET/CT offers high detection rates in early BCR after radical prostatectomy, especially among patients with low PSA values.

MRI targeted biopsy dramatically increases detection of clinically significant prostate cancer while reducing the risk of indolent cancer detection.

108 Background: MRI fusion prostate biopsy has been shown to improve detection of clinically significant prostate cancer, however the degree of this benefit is poorly characterized in large clinical trials. Methods: 1750 MRI targeted plus sextant biopsies were performed in 1742 male patients from 2007 to 2017. Patient demographics, PSA, prostate volume, primary and secondary Gleason scores, Johns Hopkins Grade Groups, number of MRI targeted lesions, number of cores obtained, and biopsy yield were recorded. Results: The patient population consisted of men averaging 62.9-year-old (36-86) with a mean PSA 9.6ng/mL, and prostate volume of 59.2 ml. A total of 804 cancers were detected on sextant biopsy and 839 were detected on MRI targeted biopsy. Relative to targeted biopsy, sextant biopsy detected only significantly more Gleason 6 disease (14% vs 21.5%, p &lt; 0.0001) than targeted biopsy. Targeted biopsy detected more Gleason 7 (21% vs 16.6%, p = 0.0009) and Gleason 8-10 (13.4% vs 9.4%). Additionally, Gleason 7 sub-stratification demonstrated substantially more Gleason 4+3 detection in targeted group vs sextant biopsy (4% vs 0.5%, p &lt; 0.0001). When stratified by Grade Group targeted biopsy detected 76% more Grade Group 3-5 cancers (p &lt; 0.0001) and 17.7% less Gleason Group 1-2 cancers (p &lt; 0.0001). Only 1.7% of Grade Group 3-5 cancers were detected on sextant biopsy alone, where as 15.7% of Grade Group 3-5 cancers were detected on targeted biopsy alone. Conclusions: MRI targeted biopsy significantly increases the likelihood of detecting clinically significant cancer and decreases the risk of indolent cancer detection. These finding strongly support the use of MRI targeted biopsy when possible.

Prostate cancer (PCa) incidence and severity in 821 hypogonadal men with and without testosterone therapy (TTh) in a controlled, observational registry implying more than 7,000 patient-years.

304 Background: Guidelines by AUA and EAU state that there is no evidence for an increased PCa risk for testosterone (T) treatment in hypogonadal men. Methods: In a registry study initiated in 2004 in a urology practice, 428 hypogonadal men (T≤350 ng/dL) received T undecanoate 1000 mg every 3 months following an initial 6-month interval for up to 13 years (T-group). 393 hypogonadal men (age range 51-74) opted against TTh (CTRL). Suspicion of or active PCa was excluded by transrectal ultrasound, digital rectal examination and PSA before treatment/observation initiation. Examinations were repeated between one and four times per year. Biopsies were performed when indicated according to EAU Guidelines. Results: In the T-group, 12 (2.8%) , in CTRL, 42 men (10.9%) were diagnosed with PCa. The mean baseline age of PCa patients was 64.9 years in the T-group and 64 in CTRL.In the T-group, the average time span between day of first injection and positive biopsy was 14.2 months (range: 5-18). No patient was diagnosed with PCa beyond 18 months of TTh. In CTRL, PCa was diagnosed at any time during the observation time. In the T-group, radical prostatectomy (RP) was performed in all men. All but 3 patients had Gleason score (GS) ≤6, and all but 1 had a primary GS of 3. Tumor grade was G2 in all 12 (100%), tumor stage T2a in 7 (58%), T2b in 3 (25%), and T2c in 2 (17%) patients. All but 2 patients are back on TTh after an average time of 25 months. In CTRL, RP was performed in all but 6 patients who received radiation therapy (RT). GS was ≤6 in 2 patients, 7 men had a GS of 7, 21 a GS of 8, and 12 a GS of 9. 4 men had a primary Gleason score of 3, 29 had 4, and 9 had 5. Tumor grade was G2 in 9 (21%) and G3 in 33 (79%) patients, tumor stage T2a in 2 (5%), T2c in 1 (2%), T3b in 15 (36%) and T3c in 24 (57%) patients. In CTRL, biochemical recurrence occurred in 11 (26%) patients. These patients received androgen deprivation therapy (ADT). 12 (34%) patients died of whom 7 were on ADT. In the T-group, no biochemical recurrences or deaths occurred during the observation time. Conclusions: Less PCa occurred and severity was lower in testosterone-treated hypogonadal patients compared to untreated hypogonadal controls.

Performance characteristics of prostate-specific antigen density and biopsy primary Gleason score to predict biochemical failure in patients with intermediate prostate cancer who underwent radical prostatectomy.

BackgroundPrognosis for intermediate-risk prostate cancer (PCa) remains variable; therefore, we aimed to investigate high-risk factors for biochemical recurrence (BCR), and intermediate-risk PCa using radical prostatectomy to identify patients having equivalent BCR-free survival rates when compared to high-risk PCa.Patients and methodsA total of 441 medical records were analyzed, including those of 169 intermediate-risk and 272 high-risk PCa patients. Risk factors for time to BCR were tested and analyzed using Kaplan–Meier survival analysis, log-rank tests, and Cox proportion hazards models.ResultsIn the intermediate-risk group, prostate-specific antigen density (PSAD) and primary Gleason pattern were significant preoperative risk factors for BCR. Moreover, BCR-free survival of patients in the intermediate-risk group with a higher PSAD (>0.5 ng/mL/cm3) was comparable with that of patients in the high-risk group (P=0.735). When combining primary Gleason pattern 4 and 3 with PSAD cut-offs 0.3–0.7 ng/mL/cm3, we found that BCR-free survival of patients in the intermediate-risk group with a primary Gleason pattern 4 and PSAD >0.3 ng/mL/cm3 was comparable with that of patients in the high-risk group (P=0.463).ConclusionPSAD and primary Gleason pattern are potential risk factors associated with biochemical failure in intermediate-risk PCa patients after radical prostatectomy. Regarding significant differences in prognosis according to PSAD as well as primary Gleason pattern on biopsy, a subset of the intermediate-risk patients could be identified with outcomes that were equivalent to that of high-risk patients.