bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ability of STAR-CAP staging system to prognosticate risk of subsequent therapies after initial treatment of M0 prostate cancer.
Authors: Sung Daeun , Tward Jonathan David 
Published: March 2023

310 Background: Given lower mortality rates and life expectancy loss in prostate cancer, treatment regimens must consider long-term outcomes with quality of life. Aggressiveness of treatment impacts severity of side effects and depends on the highly heterogeneous staging of the disease at onset. Staging and risk-classification systems have been developed, including STAR-CAP staging system which informs prognosis and could help with treatment intensification decisions. Compared with existing models such as the AJCC, STAR-CAP had superior performance and prognostic power for disease mortality prediction. However the risk of requiring subsequent therapies (ie salvage radiation therapy or androgen deprivation therapies after initial treatment) has not been described in STAR-CAP cohorts. Quantifying risk of subsequent therapies after initial therapies is clinically useful to help patients decide between various management strategies and whether monotherapies or multi-modality therapies may be sufficient. Methods: Patients who could be stratified by STAR-CAP system and underwent surgery or radiation therapy were identified from an institutional observational registry. Patients treated before 2010 were gathered retrospectively (n=835) and prospectively thereafter (n=2588). The primary endpoint was progression to additional therapy after primary treatment (radiation, surgery, or systemic therapy). Risk of progression accounting for STAR-CAP group was estimated using the Fine and Gray Competing risk model, with death as the competing risk. P<0.05 was considered statistically significant. Results: 3424 men diagnosed with prostate cancer underwent curative-intent treatment with surgery or radiation therapy (RT) between 1995 – 2022. The median age at diagnosis was 64.9 years (IQR 59.4 to 70.0); median follow-up time was 5.4 years. Patients with STAR-CAP 1A-1C had a statistically similar risk of requiring additional therapies, whereas those with 2A to 3B disease had a significantly and incrementally higher risk of requiring additional therapies (by group, hazard ratios and 95% CI: 2A, 1.8 (1.2 to 2.5); 2B, 2.9 (2.1 to 4.2); 2C, 3.4 (2.4 to 4.9); 3A, 5.7 (3.9 to 8.3); 3B, 7.0 (4.4 to 11.1), all p<0.001). The 5-year risks of requiring additional therapy after surgery for a Stage 1A, 2A, and 3A patient is 9.7%, 16.2%, and 38%, respectively. The 5-year risks of requiring additional therapy after radiation with or without ADT for a Stage 1A, 2A, and 3A patient are 7.3%, 10.4% and 27.9%, respectively. Conclusions: The STAR-CAP grouping system can prognosticate risk of requiring additional therapies after primary treatment of localized prostate cancer. The lower risk of subsequent therapy seen in RT patients is likely due to use of ADT with RT. Using STAR-CAP to prognosticate risk of subsequent therapies after primary treatment can help guide treatment intensification decisions upfront.
Prediction of significant prostate cancer in equivocal MRI lesions: A high-volume international multicenter study.
Authors: Sigle August , Borkowetz Angelika , von Hardenberg Jost , Drerup Martin , Kornienko Kira , Gratzke Christian , Mahjoub Samy 
Published: March 2023

311 Background: The decision of performing prostate biopsy in men with equivocal findings in prostate magnetic resonance imaging (MRI) is challenging as they have a low but still relevant risk of harboring significant prostate cancer (sPC). Objective: To identify clinical predictors of sPC in men with equivocal findings in prostate MRI. Secondly, we aimed to analyze the hypothetical effect of incorporating prostate-specific antigen density (PSAD) into biopsy decision. Methods: We analysed a retrospective multinational cohort from 10 academic centers comprising 1476 men who underwent combined prostate biopsy (MRI-targeted plus systematic) between 02/2012 – 04/2021 due to an equivocal lesion found in prostate MRI (Prostate Imaging Reporting and Data System 3). Primary outcome was the detection of sPC (ISUP ≥ 2) in combined biopsy. Regression analysis was performed to identify predictors for this outcome. Descriptive statistics were applied to evaluate the hypothetical effect of involving PSAD into biopsy decision. Results: 273/1476 (18.5%) men were diagnosed with sPC by combined biopsy. MRI-targeted biopsy diagnosed less sPC as compared to combined strategy: 183/1476 (12.4%) vs. 273/1476 (18.5%), p<0.01. Regression analysis confirmed age (OR 1.10 [95% CI: 1.05 – 1.15]; p < 0.001), prior negative biopsy (OR 0.46 [0.24 – 0.89]; p = 0.022) and PSAD (p<0.001) as independent predictors for sPC. Applying a PSAD cut-off of 0.15 for biopsy decision, 817/1398 (58.4%) of the biopsy procedures would have been avoided at the cost of missing sPC in 91 (6.5%) men. Limitations were the retrospective design, heterogeneity of the study cohort due to the long inclusion period and a missing central revision of MRI. Conclusions: Age, previous biopsy status and PSAD were found independent predictors of sPC in men with equivocal prostate MRI. Implementation of PSAD into biopsy decision can avoid a large proportion of unnecessary biopsies. Clinical parameters such as PSAD need validation in a prospective setting.
Detection of true positive M1 lesions by 18F-rhPSMA-7.3 PET in newly diagnosed prostate cancer: Results from the phase 3 prospective LIGHTHOUSE study.
Authors: Koontz Bridget F. ,   LIGHTHOUSE Study Group
Published: March 2023

315 Background: Radiohybrid (rh) 18F-rhPSMA-7.3 is a novel high affinity prostate specific membrane antigen (PSMA)-targeting positron emission tomography (PET) radiopharmaceutical. The LIGHTHOUSE study (NCT04186819) evaluated the diagnostic performance of 18F-rhPSMA-7.3 in newly diagnosed prostate cancer. Here we report the 18F-rhPSMA-7.3 verified detection rate (VDR), defined as the proportion of patients with M1 lesions identified by blinded image evaluation (BIE) and subsequently confirmed true positive (TP) by biopsy or confirmatory imaging. Methods: Men with treatment-naïve, unfavorable intermediate to very high-risk prostate cancer who were scheduled to undergo radical prostatectomy underwent PET 50-70 min after IV administration of 296 MBq 18F-rhPSMA-7.3. Onsite readers interpreted the images before submission for BIE by 3 central readers.Ifthe onsite read indicated M1 disease, verification (by biopsy, surgery or additional imaging) of PET-positive M1 lesions was attempted prior to treatment. 18F-rhPSMA-7.3 M1 VDR was evaluated amongall study patients without major protocol deviations. Results: Of the 335 men analyzed (median [range] PSA, 8.89 [1.15-120] ng/mL), 58 (17%) had M1 lesions by majority read. In total, 34 (10%) had verified M1 lesions with individual readers’ M1 VDR ranging from 10-15%. By region, verified M1 lesions were most common in bone, ranging from 6.0-11% across readers (majority read, 6.6%). Similar data were shown among a subgroup who had negative baseline conventional imaging. In these patients, the VDR ranged from 8.9-13% across readers (majority read, 8.6%). Again, bone showed the highest regional VDR, ranging from 4.8-9.2% (majority read, 5.1%). Conclusions: Further to its clinically meaningful sensitivity and specificity for pelvic lymph node metastases (reported separately), here we show 18F-rhPSMA-7.3 PET to be a useful staging tool, as distant metastatic lesions were verified in 10-15% of newly diagnosed patients with unfavorable intermediate to very high-risk prostate cancer. Determining the presence of M1 disease prior to surgery may help guide treatment planning by identifying patients for whom surgery is the optimal approach, or those for whom alternatives such as radiation therapy and/or androgen deprivation may be more suitable. Clinical trial information: NCT04186819 . [Table: see text]
Positron emission tomography of patients with confirmed prostate cancer using 64Cu-SAR-bisPSMA.
Authors: Emmett Louise , Wong Veronica , Lenzo Nat , Lengyelova Eva , Biggin Colin 
Published: March 2023

318 Background: Prostate cancer (PC) is the second most frequent malignancy in men worldwide. 68Ga-PSMA-11 is one of the most widely used radiotracers for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with PC and is part of standard clinical practice at many centres. Due to the longer half-life and shorter positron range of copper-64 (t1/2=12.7 hours; mean positron range=0.56 mm), a novel PSMA-targeting radiotracer labelled with this radionuclide, 64Cu-SAR-bisPSMA, has the potential to provide advantages over 68Ga-PSMA-11 (t1/2=68 minutes; mean positron range=3.5 mm). The 12.7 hour half-life of Cu-64 allows the central manufacturing of 64Cu-SAR-bisPSMA with a product shelf-life of up to 2 days. The longer half-life enables PET imaging from 1 to 72 hours after administration which offers greater flexibility in terms of scheduling of patients and may translate into detection of additional lesions due to increased Standardized Uptake Values (SUV) in the lesions relative to background following biological clearance of the tracer from organs over time. The shorter positron range may lead to improved resolution on the scan and thus, better detection of small lesions, including those that are in close proximity to each other, or to organs involved in clearance of the product such as the bladder and kidneys. In addition to the potential imaging and supply benefits of Cu-64, current generation PSMA targeting agents such as 68Ga-PSMA-11 have only a single targeting functional group. 64Cu-SAR-bisPSMA has two PSMA-targeting functional groups, which can lead to improved tumor uptake and retention. This was shown in a preclinical study, where 64Cu-SAR-bisPSMA outperformed the monomeric 64Cu-SAR-PSMA with respect to both tumor uptake and retention (Zia et al, 2019). Methods: Patients with untreated, histopathology-proven, intermediate- to high-risk PC, planned for radical prostatectomy underwent 68Ga-PSMA-11 PET/CT per institutional practice and were subsequently allocated to 1 out of 3 dose cohorts (1:1:3) to receive either 100 MBq, 150 MBq or 200 MBq of 64Cu-SAR-bisPSMA, respectively. A PET/CT was acquired at 3-hours (±1 hour) post-injection of 64Cu-SAR-bisPSMA. Two independent, blinded, central readers assessed the detection of primary PC on the 200 MBq 64Cu-SAR-bisPSMA PET/CTs as the primary endpoint. To compare the intensity of lesions on 68Ga-PSMA-11 and 64Cu-SAR-bisPSMA PET, both readers determined the SUVs (SUVmax, SUVmean) and tumour-to-background ratio (ratio of lesion SUVmax and background SUVmean) in up to 5 concordant lesions between 68Ga-PSMA-11 and 64Cu-SAR-bisPSMA PET/CT as an exploratory endpoint. Clinical trial information: NCT04839367 .
BPH-related false positive of 68Ga-PSMA PET/CT in the diagnosis of prostate cancer: The Achilles heel of biopsy-free radical prostatectomy?
Authors: Tang Wei , Tang Yongxiang , Qi Lin , Zhang Ye , Tang Guyu , Gao Xiaomei , Hu Shuo , Cai Yi 
Published: March 2023

319 Background: Radical prostatectomy (RP) is the primary treatment for localized clinically significant prostate cancer (csPCa). However, its application is generally based on prior pathological diagnosis. 68Ga-prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) has recently been found to have high diagnostic efficacy and is considered promising in biopsy-free RP. Notably, inadequate specific or positive predictive value of imaging diagnosis strategy could become the Achilles’ Heel of biopsy-free RP. For 68Ga-PSMA PET/CT, the expression of PSMA in benign prostatic hyperplasia (BPH) tissue and its related positive reaction, which can reduce the specificity of diagnosis, are important concerns affecting the imaging diagnosis of PCa as well as the feasibility of biopsy-free RP. Currently, no study has explored the BPH-related false positive rate of 68Ga-PSMA PET/CT in the detection of PCa. Furthermore, the influence of maximum standardized uptake value (SUVmax) on biopsy-free RP is also poorly characterized. Methods: To investigate BPH-related false positive rate of 68Ga-PSMA PET/CT in detecting PCa and the influence of SUVmax on biopsy-free RP, a retrospective descriptive observational study was conducted. Patients who received 68Ga-PSMA PET/CT because of clinical suspicion of PCa based on elevated prostate-specific antigen (> 4ng/ml) or abnormal digital rectal examination and subsequently were confirmed to be BPH or PCa by systematic biopsy or targeted biopsy (TB) were included. The receiver operating characteristic curve was generated for SUVmax values, from which the area under the curve (AUC) and the Youden index was calculated. Sensitivity and specificity were calculated based on the cutoffs. Results: A total of 89 BPH and 94 PCa patients who met the inclusion criteria were included. 27 of the 89 BPH cases were considered 68Ga-PSMA PET/CT positive, all dominant lesions were confirmed to be BPH tissue through TB, and thus, were regarded as BPH-related false positive. The BPH-related false positive rate of 68Ga-PSMA PET/CT in the detection of PCa was 30.3%. SUVmax could effectively distinguish BPH and grade group (GG) one patients with an AUC of 0.8562 and could potentially benefit biopsy-free RP by avoid BPH-related misdiagnosis and GG one-related overtreatment. The optimal SUVmax cutoff value was 9.750 with a sensitivity of 64.71% and a specificity of 97.22%. Given the pivotal role of specificity in biopsy-free RP, we investigated the optimal SUVmax cutoff under when the specificity was 100%. The result was 14.60, with a sensitivity of 41.18% and a specificity of 100%. Conclusions: Our results revealed, for the first time, the BPH-related false positive rate of 68Ga-PSMA PET/CT in the primary diagnosis of PCa. Using SUVmax values in biopsy-free RP can effectively exclude both BPH and GG one patients.
Comparison of transperineal and transrectal biopsy approaches to detect clinically significant prostate cancer in patients undergoing MRI fusion prostate biopsy: A lesion level analysis.
Authors: Wood Andrew , Khooblall Prajit , Benidir Tarik , Bullen Jennifer , Ward Ryan , Purysko Andrei , Weight Christopher J. 
Published: March 2023

320 Background: The use of transperineal (TP) prostate biopsy has gained in popularity due to reduced risk of infectious events, however evidence regarding cancer detection rates versus transrectal (TR) prostate biopsy is lacking. Our objective was to examine whether transperineal (TP) MRI-fusion targeted prostate biopsy (MRI-TBx) resulted in improved detection of clinically significant prostate cancer (csPCa), defined as International Society of Urological Pathology (ISUP) grade group ≥2, as compared to TR MRI-TBx. Methods: Retrospective review of all patients who underwent MRI-TBx at a tertiary care academic center. A cohort of patients who underwent TP MRI-TBx was compared to a second cohort of patients who underwent TR MRI-TBx. The primary outcome of interest was detection of csPCa, however detection of ISUP grade group 1 prostate cancer (GG1 PCa) was also examined. Analyses were performed on a lesion level basis. Multivariable logistic regression analyses were performed to assess for predictors of csPCa detection. Results: A total of 389 and 1144 lesions from 303 and 836 patients who underwent TP MRI-TBx vs TR MRI-TBx respectively were included in the analysis. The detection of both csPCa (39.6% vs 29.6%, p <0.001) and GG1 PCa (34.4% vs 21.1%, p <0.001) was higher for TP MRI-TBx vs. TR MRI-TBx. On multivariable analysis adjusted for age, prior biopsy status, Prostate Imaging–Reporting and Data System (PIRADS) score, prostate volume, PSA, size of PIRADS lesion, and zone of PIRADS lesion, TP MRI-TBx remained an independent predictor of csPCa (odds ratio [OR] 1.49, 95% CI 1.13-1.98). Surprisingly, transperineal biopsy was not a significant predictor of csPCa for Transition zone lesions (OR 1.24, p = 0.35), but was for Peripheral zone lesions (OR = 1.84, p < 0.001). Conclusions: Performance of TP MRI-TBx demonstrates improved detection of both csPCa and GG1 PCa. This difference is not dependent on anterior/transition zone location. This has important implications in risk assessment for localized prostate cancer, including counseling for active surveillance and definitive management strategies. [Table: see text]
The impact of focal therapy tumor boards, including prostate magnetic resonance imaging overreads, in refining the selection candidacy for focal therapy patients: A prospective study.
Authors: Benidir Tarik , Lone Zaeem M , Wood Andrew , Abdallah Nour , Nguyen Jane , Kaouk Jihad , Stein Robert , Haywood Samuel , Abouassaly Robert , Almassi Nima , Weight Christopher J. , Olivares Ruben , Purysko Andrei 
Published: March 2023

324 Background: Focal therapy (FT) for prostate cancer is increasingly recognized as an adequate therapeutic option in well selected men. Nevertheless, in-field and out-of-field recurrences at one year from treatment are notable. A multidisciplinary tumor board geared towards improving focal therapy (FTTB) patient selection is a novel concept which has not been explored. The impact of conducting prostate MRI-overreads during FTTB may also help refine FT candidacy and potentially reduce failure rates. We aimed to explore the value of a dedicated FTTB. Therein, we also evaluated the impact of prostate MRI overreads and its overall influence on FT candidacy. Methods: Single center, prospective study, incorporating a multidisciplinary bi-weekly FTTB (2021-2022) on patients being considered for FT. All prostate MRIs were re-reviewed by a single GU radiologist with >10 years prostate MR imaging experience. Outside pathology, when requested, was also re-reviewed. The impact of such tumor boards, and specifically MRI overreads on patient candidacy are presented. Results: Forty-five patients were presented at our FTTB over the span of one year. Patient demographics are presented. Thirty-nine patients were treatment naïve while six had prior radiation +/- ADT. MRI overread was performed on all treatment naïve patients (39/45, 87%) while pathology overreads on 11/45 (24.4%) Four patients were excluded upfront due to not meeting safety criteria for FT (Urolift device (n=1), J-pouch (n=1), suspicions of metastasis at time of consideration (n=2). Among those with MRI overreads 44.7% (17/39) were found to have findings that negatively impacted eligibility for FT like lesion crossing anteriorly to the urethra occurred in (9/17), multifocal disease (8/17), discordance of lesion on prior MRI (3/17) and lesion abutting rectal wall (1/17). Pathology re-review changed management for 3/11 patients with 2/3 being downgraded to GG1 disease and opting for active surveillance. Following multidisciplinary tumor boards, twelve patients (26.7%) were deemed candidates for FT. Conclusions: FTTB increases the selection scrutiny for FT candidates. MRI overreads are a meaningful part of FT tumor boards and can change candidacy based on new or meaningful findings. FTTB with prostate MR overreads should be considered as part of the selection process in FT decision making. [Table: see text]
The natural progression of patients with an IsoPSA value and its predictive ability of clinically significant prostate cancer on biopsy.
Authors: Abdallah Nour , Benidir Tarik , Lone Zaeem M , Zhang Ao , Wood Andrew , Curry Caleb , Haywood Samuel , Kaouk Jihad , Abouassaly Robert , Klein Eric A. , Weight Christopher J. 
Published: March 2023

325 Background: IsoPSA is a structure-based serum assay exploring the spectrum of possible prostate-specific antigen (PSA) isoforms. It was shown to outperform total and percent-free PSA in detecting clinically significant prostate cancer (csPCa) (grade group (GG) ≥2 on biopsy). IsoPSA reduced unnecessary biopsies and magnetic resonance imaging (MRI). We sought to compare the outcomes of eventual biopsy and imaging of surveilled patients with an initially normal or high IsoPSA, thus assessing IsoPSA’s prospective predictive ability of csPCa. Methods: We performed a single-center retrospective review of patients who underwent IsoPSA testing from 2017-present. Data was dichotomized into patients with normal (≤6) and high IsoPSA (>6). We collected the outcomes of any consequent IsoPSA and PSA test, prostate biopsy and MRI. We calculated the statistical IsoPSA’s characteristics for the prediction of csPCa on biopsy. Results: The median follow-up time of 811 patients who underwent IsoPSA testing was 18 months (IQR, 16.5-20). Among 443 patients with initial low IsoPSA, 5 (1.1%) had a csPCa on a subsequent biopsy, 19 (4.3%) subsequent high IsoPSA, 122 (27.5%) rising PSA, and 22 (5%) csPCa on MRI. Among 368 patients with initial high IsoPSA, 105 (28.5%) had a csPCa on a subsequent biopsy and 106 (28.8%) on an MRI. The sensitivity of IsoPSA to predict csPCa was 95.5%, and the NPV was 94.8%. Among 124 patients with high IsoPSA and initial negative biopsy, 110 had a subsequent negative and 14 a positive biopsy (10GG1 (8.1%), 4 ≥GG2 (3.2%)), with a respective median IsoPSA of 7.2 and 9.6 (p=0.007). An IsoPSA>10 generated an OR of csPCa of 7.2 (95%CI 2.1-25.2, p=0.0005). Conclusions: In 18-month follow-up, 1.1% of patients with normal IsoPSA developed csPCa compared to 28.5% of patients with high IsoPSA. In the cohort of patients with high IsoPSA and initially negative biopsy, 3.2% eventually developed csPCa, however, having a significantly higher IsoPSA than those who remained negative. The odds of having csPCa were 7 times higher with IsoPSA>10. [Table: see text]