Biochemical Recurrence In Patients Research Articles

Comprehensive Analysis of Perioperative Factors Influencing the Risk of Biochemical Recurrence in Patients with Radical Prostatectomy.

To analyze the perioperative factors that influence the risk of biochemical recurrence (BCR) in patients with localized PCa undergoing radical prostatectomy Materials and Methods: A total of 457 patients, operated by 2 surgeons in our high-volume oncological center were included in the initial database. Patients who underwent RP for clinically localized PCa in our clinic from 2016 to 2021 were included in the study. Perioperative data were retrospectively reviewed for this study. Follow-up data including post-operative PSA and adjuvant treatment was prospectively gathered by contacting the patients or from the follow-up consultation. Final database was composed of 366 patients who underwent open or 3D laparoscopic RP. Statistical analysis was performed to emphasize the most powerful parameters that influence the BCR. Results: Accounting for multivariable analysis, 4 parameters were statistically significant: initial PSA (iPSA), Gleason score, vascular involvement and positive surgical margins. For the group of patients with no positive margins, 3 parameters were statistically significant: iPSA above 10,98 ng/mL (AUC=0,71); lymph node involvement and Gleason score. Multivariable Cox regression showed that positive margins and iPSA had a significant impact on the time to BCR. Patients that received adjuvant therapy were excluded from the study. Out of the whole cohort, 27,3% of patients presented BCR. Perioperative factors need to be carefully analyzed and a detailed follow-up needs to be conducted in order to assess the risk of biochemical recurrence, resulting in the optimal time for adjuvant treatment implementation.

SnRNAs from Radical Prostatectomy Specimens Have the Potential to Serve as Prognostic Factors for Clinical Recurrence after Biochemical Recurrence in Patients with High-Risk Prostate Cancer.

In patients with high-risk prostate cancer (HRPC) after radical prostatectomy (RP), biochemical recurrence (BCR) increases the risk of distant metastasis. Accordingly, additional prognostic biomarkers are required to identify the subpopulation of patients with HRPC who develop clinical recurrence (CR) after BCR. The objective of this study was to identify biomarkers in formalin-fixed paraffin-embedded (FFPE) RP samples that are prognostic for CR in patients with HRPC who experience BCR after RP (post-RP BCR). First, we performed a preliminary RNA sequencing analysis to comprehensively profile RNA expression in FFPE RP samples obtained from patients with HRPC who developed CR after post-RP BCR and found that many snRNAs were very abundant in preserved FFPE samples. Subsequently, we used quantitative polymerase chain reaction (qPCR) to compare the expression levels of highly abundant snRNAs in FFPE RP samples from patients with HRPC with and without CR after post-RP BCR (21 CR patients and 46 non-CR patients who had more than 5 years of follow-up after BCR). The qPCR analysis revealed that the expression levels of snRNA RNU1-1/1-2 and RNU4-1 were significantly higher in patients with CR than in patients without CR. These snRNAs were significantly correlated with clinical recurrence-free survival (RFS) in patients with HRPC who experienced post-RP BCR. Furthermore, snRNA RNU1-1/1-2 could serve as an independent prognostic factor for clinical RFS in post-RP BCR of HRPC cases where known prognostic factors (e.g., Gleason score) cannot distinguish between CR and non-CR patients. Our findings provide new insights into the involvement of snRNAs in prostate cancer progression.

The superior detection rate of total-body [68Ga]Ga-PSMA-11 PET/CT compared to short axial field-of-view [68Ga]Ga-PSMA-11 PET/CT for early recurrent prostate cancer patients with PSA < 0.2ng/mL after radical prostatectomy.

[68Ga]Ga-PSMA PET imaging has been extensively utilized for the detection of biochemical recurrence (BCR) in prostate cancer. However, the detection rate declines to merely 10-40% when PSA levels are < 0.2ng/mL employing short axial field-of-view (SAFOV) PET. Prior studies exhibited superior detection rates with total-body [68Ga]Ga-PSMA-11 PET compared to SAFOV [68Ga]Ga-PSMA-11 PET in BCR patients with PSA > 0.2ng/mL. Nevertheless, the diagnostic utility of total-body [68Ga]Ga-PSMA-11 PET for BCR patients when PSA is < 0.2ng/mL remains unclear. This study aimed to assess whether total-body [68Ga]Ga-PSMA-11 PET/CT could improve the detection rate compared to SAFOV [68Ga]Ga-PSMA-11 PET/CT in BCR patients with PSA < 0.2ng/mL. Eighty BCR patients with PSA < 0.2ng/mL underwent total-body [68Ga]Ga-PSMA-11 PET/CT. These patients were matched by baseline qualities to another 80 patients who received SAFOV [68Ga]Ga-PSMA-11 PET/CT. The detection rates of total-body [68Ga]Ga-PSMA-11 PET/CT and SAFOV [68Ga]Ga-PSMA-11 PET/CT were compared utilizing a chi-square test and stratified analysis. Image quality of total-body [68Ga]Ga-PSMA PET/CT and SAFOV [68Ga]Ga-PSMA-11 PET/CT was assessed based on subjective scoring and objective parameters. The objective parameters measured were SUVmax, SUVmean, standard deviation (SD) of SUV, and signal-to-noise ratio (SNR) of liver and gluteus maximus. The image quality of total-body [68Ga]Ga-PSMA PET/CT was superior to that of SAFOV [68Ga]Ga-PSMA-11 PET/CT in both early and delayed scans. The detection rate of total-body [68Ga]Ga-PSMA PET/CT for BCR patients with PSA < 0.2ng/mL was significantly higher than that of SAFOV [68Ga]Ga-PSMA-11 PET/CT (73.75% vs. 43.75%, P < 0.001). Total-body [68Ga]Ga-PSMA PET/CT resulted in noteworthy modifications to the treatment regimen when contrasted with SAFOV [68Ga]Ga-PSMA-11 PET/CT. In BCR patients with PSA < 0.2ng/mL, total-body [68Ga]Ga-PSMA-11 PET/CT not only demonstrated a significantly higher detection rate compared to SAFOV [68Ga]Ga-PSMA-11 PET/CT but also led to significant alterations in treatment regimens.

Abstract 299: FAP/αSMA association with tumor visibility and progression in prostate cancer

Abstract Introduction Prostate cancer (PCa) ranks as the second most frequently diagnosed cancer in the male population worldwide. The challenge in effectively managing PCa is the absence of well-established biological markers, which often leads to both over and under treatment. To address this issue, a deeper understanding of the molecular alterations within PCa is essential for more accurate patient stratification. In this research, we embark on a comprehensive examination of how the presence of fibroblast activation protein (FAP) and alpha smooth muscle actin (αSMA) in PCa tissue associates with the visibility of the disease in Magnetic Resonance Imaging (MRI) and their impact on cancer progression. The objective of this study is to analyze cell compartmental expression of FAP and aSMA using an AI based image analysis method. We also study the role of FAP and αSMA expression in predicting disease progression and mortality. Materials and Methods We applied FAP (ab207178, Abcam)/αSMA (M0851, DAKO) double chromogen immunohistochemical (IHC) staining to three independent cohorts of formalin-fixed paraffin-embedded (FFPE) prostate cancer tissue microarrays. All together, we analyzed 835 patients’ samples. First cohort consists of 387 patients with preoperative multiparametric MRI and robot-assisted laparoscopic prostatectomy (RALP) as primary treatment. Second cohort was case vs control cohort of Grade group 2-4 localized PCa at radical prostatectomy (RP) with 168 patients. Third cohort consists PCa patents from continuous, population-based collection of radical prostatectomies of 319 patients. Image analysis was performed with Aiforia Create, which is cloud-based deep-learning artificial intelligence software that provides platform for training and validating automated image analysis pipelines using convolutional neural networks. Analysis algorithm in this project was based on semantic, pixel-level area segmentation. Results FAP expression was higher and αSMA lower in MRI-visible tumors compared with MRI-invisible tumors. Stromal and epithelial FAP expression associate with tumor progression. We could also see statistically significant differences in FAP positivity between clinically significant (GS ≥7) and insignificant (GS ≤6) tumors. Hazard ratios imply that FAP and αSMA have significant impact on risk of biochemical recurrence in patients with MRI-visible tumors. Conclusions FAP is closely linked to tumor MRI visibility, cancer progression, and Gleason scores, marking it as a valuable biomarker in PCa assessment. High stromal αSMA is primarily associated with MRI visibility. Our automated AI-based image analysis method has demonstrated reliability, aligning with our previous findings. This advances the potential for more accurate and efficient prostate cancer diagnosis and prognosis, offering a potential benefit to future patient care. Citation Format: Jenni Säilä, Timo-Pekka Lehto, Annabrita Schoonenberg, Katja Välimäki, Andrew Erickson, Antti Rannikko, Olli Kallioniemi, Tuomas Mirtti, Teijo Pellinen. FAP/αSMA association with tumor visibility and progression in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 299.

Risk classification system using the detailed positive surgical margin status for predicting biochemical recurrence after robot-assisted radical prostatectomy.

This study aimed to evaluate the risk classification system using the detailed positive surgical margin (PSM) status to predict biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP). We retrospectively analyzed 427 patients who underwent RARP between January 2016 and March 2020. We investigated risk factors for BCR using univariate and multivariate Cox proportional hazard regression models. The biochemical recurrence-free survival (BRFS) rate was assessed using the Kaplan-Meier method. The median follow-up period was 43.4 months and 99 patients developed BCR. In the multivariate analysis, maximum PSM length>5.0mm and the International Society of Urological Pathology grade group (ISUP GG) at the PSM ≥3 were predictive factors for BCR in patients with a PSM. In the multivariate analysis, these factors were also independent predictive factors in the overall study population, including patients without a PSM. We classified the patients into four groups using these factors and found that the 1-year BRFS rates in the negative surgical margin (NSM) group, low-risk group (PSM and neither factor), intermediate-risk group (either factor), and high-risk group (both factors) were 94.9%, 94.5%, 83.1%, and 52.9%, respectively. The low-risk group showed similar BRFS to the NSM group (p=0.985), while the high-risk group had significantly worse BRFS than the other groups (p<0.001). Maximum PSM length>5.0mm and ISUP GG at the PSM ≥3 were independent predictive factors for BCR after RARP. Risk classification for BCR using these factors is considered to be useful and might help urologists decide on additional treatment after RARP.

Head-to-head comparison of prostate-specific membrane antigen positron emission tomography/computed tomography and multiparametric magnetic resonance imaging in the detection of biochemical recurrence of prostate cancer: a systematic review and meta-analysis

Our main goal of this meta-analytical analysis was to evaluate the diagnostic effectiveness of prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) against multiparametric magnetic resonance imaging (mpMRI) in the context of identifying biochemical recurrence in patients with prostate cancer (PCa). A thorough search covering articles published until March 2023 was carried out across major databases such as PubMed, Embase, and Web of Science. Studies examining the direct comparison of PSMA PET/CT and mpMRI in patients with PCa suffering biochemical recurrence were included in the inclusion criteria. Using the renowned Quality Assessment of Diagnostic Performance Studies-2 technique, each study's methodological rigor was assessed. We analyzed data from six eligible studies involving 290 patients in total. The combined data showed that for PSMA PET/CT and mpMRI, respectively, the pooled overall detection rates for recurrent PCa after definitive treatment were 0.69 (95% confidence interval [CI]: 0.45-0.89) and 0.70 (95% CI: 0.44-0.91). The detection rates for local recurrence were specifically 0.52 (95% CI: 0.39-0.65) and 0.62 (95% CI: 0.31-0.89), while they were 0.50 (95% CI: 0.26-0.74) and 0.32 (95% CI: 0.18-0.48) for lymph node metastasis. Notably, there was no discernible difference between the two imaging modalities in terms of the overall detection rate (P = 0.95). The detection rates for local recurrence and lymph node metastasis did not differ statistically significantly (P = 0.55, 0.23). The performance of PSMA PET/CT and mpMRI in identifying biochemical recurrence in PCa appears to be comparable. However, the meta-analysis' findings came from research with modest sample sizes. In this context, more extensive research should be conducted in the future.

Pretreatment prostate-specific antigen density as a predictor of biochemical recurrence in patients with prostate cancer: a meta-analysis

BackgroundA consensus has not been reached on the value of prostate-specific antigen density (PSAD) as a predictor of biochemical recurrence of prostate cancer. This meta-analysis aimed to evaluate the association between PSAD and biochemical recurrence of prostate cancer after primary treatment.MethodsTwo authors systematically searched PubMed, Web of Science, and Embase databases (up to August September 10, 2023) to identify studies that assessed the value of pretreatment PSAD in predicting biochemical recurrence after primary treatment (radical prostatectomy or radiotherapy) of prostate cancer. A random effect model was used to pool adjusted hazard ratios (HR) with 95% confidence intervals (CI) for biochemical recurrence.ResultsNine studies with 4963 patients were eligible for the meta-analysis. The reported prevalence of biochemical recurrence ranged from 4 to 55.1%. For patients with higher PSAD compared to those with low PSAD, the pooled HR of biochemical recurrence was 1.59 (95% CI 1.21–2.10). Subgroup analysis showed that the pooled HR of biochemical recurrence was 1.80 (95% CI 1.34–2.42) for patients who received radical prostatectomy, and 0.98 (95% CI 0.66–1.45) for patients who received radiotherapy.ConclusionsElevated pretreatment PSAD may be an independent predictor for biochemical recurrence of prostate cancer after radical prostatectomy. Determining PSAD could potentially improve the prediction of biochemical recurrence in patients with prostate cancer.

Significance of the cribriform morphology area ratio for biochemical recurrence in Gleason score 4 + 4 prostate cancer patients following robot-assisted radical prostatectomy.

In prostate cancer, histological cribriform patterns are categorized as Gleason pattern 4, and recent studies have indicated that their size and percentage are associated with the risk of biochemical recurrence (BCR). However, these studies included a mixture of cases with various Gleason scores (GSs). We therefore examined the prognostic value of the area and percentage of cribriform patterns in patients with GS 4 + 4 prostate cancer. We investigated 108 patients with GS 4 + 4 prostate cancer who underwent robot-assisted radical prostatectomy (RARP). After digitally scanning the hematoxylin and eosin-stained slides, we measured the area of the entire cancer and cribriform patterns. Predictive factors for BCR were explored using log-rank test and Cox proportional hazard model analyses. Sixty-seven (62.0%) patients had a cribriform pattern in RARP specimens, and 32 (29.6%) experienced BCR. The median total cancer area, cribriform pattern area, and percentage of cribriform pattern area (% cribriform) were 427.70 mm2 (interquartile range [IQR], 171.65-688.53 mm2 ), 8.85 mm2 (IQR, 0-98.83 mm2 ), and 2.44% (IQR, 0%-33.70%), respectively. Univariate analyses showed that higher preoperative serum prostate-specific antigen (PSA) levels, positive resection margins, advanced pathological T stage, extraprostatic extension, larger total cancer area, larger cribriform morphology area, and higher % cribriform values were significantly associated with BCR. A multivariate analysis demonstrated that the PSA level (hazard ratio [HR], 1.061; 95% confidence interval [CI], 1.011-1.113; p = 0.017) and % cribriform (HR, 1.018; 95% CI, 1.005-1.031; p = 0.005) were independent predictors of BCR. An increased % cribriform value was associated with BCR in patients with GS 4 + 4 prostate cancer following RARP.

Do Phosphodiesterase Type 5 Inhibitors Increase the Risk of Biochemical Recurrence After Radical Prostatectomy?

There have been conflicting studies on the association between phosphodiesterase type 5 inhibitor (PDE5i) use and biochemical recurrence (BCR) following radical prostatectomy (RP). Our aim was to determine whether PDE5i drug exposure after RP increases the risk of BCR in patients undergoing RP. An institutional database of prostate cancer patients treated between January 2009 and December 2020 was reviewed. BCR was defined as 2 PSA measurements greater than 0.1 ng/mL. PDE5i exposure was defined using a 0 to 3 scale, with 0 representing never use, 1 sometimes use, 2 regularly use, and 3 routinely use. The risk of BCR with any PDE5i exposure, the quantity of exposure, and the duration of PDE5i exposure were assessed by multivariable Cox proportional hazards models. The sample size included 4630 patients to be analyzed, with 776 patients having BCR. The median follow-up for patients without BCR was 27 (IQR 12, 49) months. Eighty-nine percent reported taking a PDE5i at any time during the first 12 months after RP, and 60% reported doing so for 6 or more months during the year after RP. There was no evidence of an increase in the risk of BCR associated with any PDE5i use (HR 1.05, 95% CI 0.84, 1.31, P = .7) or duration of PDE5i use in the first year (HR 0.98 per 1 month duration, 95% CI 0.96, 1.00, P = .055). Baseline oncologic risk was lower in patients using PDE5i, but differences between groups were small, suggesting that residual confounding is unlikely to obscure any causal association with BCR. Prescription of PDE5i to men after RP can be based exclusively on quality of life considerations. Patients receiving PDE5is can be reassured that their use does not increase the risk of BCR.

18F-FDG PET Is Not Inferior to 68Ga-PSMA PET for Detecting Biochemical Recurrent Prostate Cancer with a High Gleason Score: A Head-to-Head Comparison Study.

Previous studies have indicated that 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in biochemical recurrence (BCR) patients with poorly differentiated prostate adenocarcinoma had higher diagnostic sensitivity than those with well differentiated adenocarcinoma, but whether the performance of FDG PET can achieve the effect of prostate-specific membrane antigen (PSMA) PET in BCR patients with a high Gleason score remains poorly understood. This study aimed to compare the efficacies of 18F-FDG PET/CT and 68Ga-PSMA PET/CT for BCR patients and evaluate whether 18F-FDG PET was not inferior to 68Ga-PSMA PET for detecting BCR with a high Gleason score. This was a retrospective, head-to-head comparative study completed at Ren Ji Hospital between May 2018 and June 2021. Patients underwent both 18F-FDG and 68Ga-PSMA PET/CT. The detection rate of BCR at the patient level and at the anatomical region level was evaluated. In total, 145 patients were enrolled in this study. 18F-FDG PET/CT (24.1%, 35/145) had lower detection rates than 68Ga-PSMA PET/CT (59.3%, 86/145; p < 0.001) at the patient level and at any anatomical region (p < 0.05). The PSA level (p < 0.001, OR = 11.026, 95% CI: 3.214-37.824) and the Gleason score (p < 0.001, OR = 20.227, 95% CI: 5.741-71.267) were independent predictive factors of the detection rate on 18F-FDG PET/CT, while the PSA level (p < 0.001, OR = 4.862, 95% CI: 2.338-10.110) was the only predictor of the detection rate on 68Ga-PSMA PET/CT. 18F-FDG PET/CT had a similar detection rate as 68Ga-PSMA PET/CT in patients with a Gleason score of 9 at the patient level (64.3% vs. 71.4%, p = 0.567) and any anatomical region (all p > 0.05), but 18F-FDG PET/CT had a lower detection rate than 68Ga-PSMA PET/CT in patients with a Gleason score of 6-8. 18F-FDG PET is not inferior to 68Ga-PSMA PET for detecting BCR with a Gleason score of 9; therefore, 18F-FDG PET/CT could be considered in BCR patients with a Gleason score of 9. However, 68Ga-PSMA is a better tracer than 18F-FDG in PET/CT for treatment decision making in BCR patients with a Gleason score of 6-8.

The impact of positive vas deferens in the biochemical relapse in patients with stage T3b prostate cancer submitted to radical Prostatectomy

The study aimed to evaluate the influence of invasion of the vas deferens and seminal vesicles in patients undergoing radical prostatectomy for stage T3b tumor on biochemical recurrence.Methods: Retrospective analysis of 53 patients submitted to radical prostatectomy with anatomopathological stage T3b, at Hospital de Clínicas da Unicamp, between 1997 and 2014. After exclusion criteria were applied, statistical analysis of 32 participants separated into 2 groups, in which 20 patients (62.5 %) without involvement of the vas deferens (group 1) and 12 (37.5%) with invasion of the vas deferens (group 2). Biochemical recurrence was defined as an increase in prostate specific antigen (PSA) greater than or equal to 0.2 ng/ml after surgery. Results: Regarding the disease-free survival analysis, group 2 has a 3.05 times greater risk of having a biochemical recurrence compared to group 1 (HR 3.05, 95% CI 1.12-8.32, p=0.03), calculated by regression of Cox and Log Rank test. Conclusion: In conclusion, this study has identified an elevated risk of biochemical recurrence in patients with both ductus deferens and seminal vesicle invasion.

Risk of Biochemical Recurrence in Patients With Grade Group 1 Prostate Cancer With Extraprostatic Extension Treated With Radical Prostatectomy.

We sought to examine the association of extraprostatic extension (EPE) with biochemical recurrence (BCR) separately in men with Grade Group (GG) 1 and GG2 prostate cancer (PCa) treated with radical prostatectomy. We reviewed our institutional database of patients who underwent radical prostatectomy for PCa between 2005 and 2022 and identified patients with GG1 and GG2 disease on final pathology. Fine-Gray competing risk models with an interaction between EPE (yes vs no) and GG (GG1 vs GG2) were used to examine the relationship between disease group and BCR-free survival. The cohort consisted of 6309 men, of whom 169/2740 (6.2%) with GG1 disease had EPE while 1013/3569 (28.4%) with GG2 disease had EPE. Median follow-up was 4 years. BCR occurred in 400/6309 (6.3%) patients. For men with GG1, there was no statistically significant difference in BCR-free survival for men with vs without EPE (subdistribution HR = 0.88; 95% CI: 0.37-2.09). However, for GG2 patients BCR-free survival was significantly worse for those with vs without EPE (subdistribution HR = 1.97, 95% CI: 1.54-2.52). Although there is a subset of GG1 PCas capable of invading through the prostatic capsule, patients with GG1 PCa and EPE at prostatectomy experience similar biochemical recurrence and survival outcomes compared to GG1 patients without EPE. However, among men with GG2, EPE connotes a worse prognosis.

Clinical Significance of Intraductal Carcinoma of the Prostate After High-Dose Brachytherapy With External Beam Radiation Therapy: A Single Institution Series and an Updated Meta-Analysis

BackgroundWe compared oncological outcomes between prostate cancer (PCa) patients with and without intraductal carcinoma of the prostate (IDC-P) after high-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT). MethodsWe performed a retrospective analysis of 138 patients with clinically high-risk, very high-risk, or locally advanced PCa who received HDR-BT with EBRT. Of these, 70 (50.7 %) patients were diagnosed with IDC-P; 68 (49.3 %) patients with acinar adenocarcinoma of prostate. The oncological outcomes, including biochemical recurrence-free survival (BCRFS) and clinical progression-free survival (CPFS), were assessed using Kaplan–Meier curves. Additionally, Cox proportional hazards models were used to identify significant prognostic indicators or biochemical recurrence (BCR). Meta-analysis of existing literatures was performed to evaluate the risk of BCR in patients with IDC-P after radiation therapy, compared to those without IDC-P. ResultsKaplan–Meier curves demonstrated significantly inferior BCRFS and CPFS in patients with IDC-P. Multivariate analysis revealed that IDC-P and Grade Group 5 status were associated with increased BCR risk. in our meta-analysis, IDC-P was associated with BCR (HR = 2.13, P = .003). ConclusionAmongst the patients who received HDR-BT, patients with IDC-P displayed significantly more rapid disease progression, compared with patients who did not have IDC-P.

Comparison of MRI-Based Staging and Pathologic Staging for Predicting Biochemical Recurrence of Prostate Cancer After Radical Prostatectomy.

BACKGROUND. Currently most clinical models for predicting biochemical recurrence (BCR) of prostate cancer (PCa) after radical prostatectomy (RP) incorporate staging information from RP specimens, creating a gap in preoperative risk assessment. OBJECTIVE. The purpose of our study was to compare the utility of presurgical staging information from MRI and postsurgical staging information from RP pathology in predicting BCR in patients with PCa. METHODS. This retrospective study included 604 patients (median age, 60 years) with PCa who underwent prostate MRI before RP from June 2007 to December 2018. A single genitourinary radiologist assessed MRI examinations for extraprostatic extension (EPE) and seminal vesicle invasion (SVI) during clinical interpretations. The utility of EPE and SVI on MRI and RP pathology for BCR prediction was assessed through Kaplan-Meier and Cox proportional hazards analyses. Established clinical BCR prediction models, including the University of California San Francisco Cancer of the Prostate Risk Assessment (UCSF-CAPRA) model and the Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) model, were evaluated in a subset of 374 patients with available Gleason grade groups from biopsy and RP pathology; two CAPRA-MRI models (CAPRA-S model with modifications to replace RP pathologic staging features with MRI staging features) were also assessed. RESULTS. Univariable predictors of BCR included EPE on MRI (HR = 3.6), SVI on MRI (HR = 4.4), EPE on RP pathology (HR = 5.0), and SVI on RP pathology (HR = 4.6) (all p < .001). Three-year BCR-free survival (RFS) rates for patients without versus with EPE were 84% versus 59% for MRI and 89% versus 58% for RP pathology, and 3-year RFS rates for patients without versus with SVI were 82% versus 50% for MRI and 83% versus 54% for RP histology (all p < .001). For patients with T3 disease on RP pathology, 3-year RFS rates were 67% and 41% for patients without and with T3 disease on MRI. AUCs of CAPRA models, including CAPRA-MRI models, ranged from 0.743 to 0.778. AUCs were not significantly different between CAPRA-S and CAPRA-MRI models (p > .05). RFS rates were significantly different between low- and intermediate-risk groups for only CAPRA-MRI models (80% vs 51% and 74% vs 44%; both p < .001). CONCLUSION. Presurgical MRI-based staging features perform comparably to postsurgical pathologic staging features for predicting BCR. CLINICAL IMPACT. MRI staging can preoperatively identify patients at high BCR risk, helping to inform early clinical decision-making. TRIAL REGISTRATION. ClinicalTrials.gov NCT00026884 and NCT02594202.

Total-body PET/CT with half-dose [68Ga]Ga-PSMA-11 for biochemical recurrent prostate cancer: comparable diagnostic value to short axial field-of-view PET/CT with full-dose [68Ga]Ga-PSMA-11.

The objective of this study was to evaluate the diagnostic performance and image quality of total-body positron emission tomography/computed tomography (PET/CT) imaging using a half-dose of [68Ga]Ga-prostate specific membrane antigen ([68Ga]Ga-PSMA) radiotracer, compared to conventional short axial field-of-view PET/CT imaging using a full dose of [68Ga]Ga-PSMA. This retrospective study enrolled 52 patients with biochemical recurrent (BCR) prostate cancer after radical prostatectomy who underwent total-body PET/CT with a half-dose (0.9-1.1MBq/kg) of [68Ga]Ga-PSMA. These patients were matched by baseline characteristics to another 52 BCR patients after prostatectomy who underwent conventional PET/CT with a full dose (1.8-2.2MBq/kg) of [68Ga]Ga-PSMA. The half-dose group was further divided into 5-min (G5) and 2-min (G2) acquisition subgroups. Image quality was assessed through subjective analysis using a 5-point scale and objective measurements of standard uptake value maximum (SUVmax), standard uptake value mean (SUVmean), background variation (BV) of the liver, blood pool, and parotid glands. Additionally, SUVmax and tumor-to-background ratio (TBR) were calculated for lesions. No significant difference in subjective image quality was found between the G2 and full-dose groups (p > 0.05). PET/CT image quality was significantly higher for the G5 versus G2 (p < 0.001) and full-dose groups (p < 0.001). TBR did not differ between the G2 and full-dose groups (4.23 ± 5.21 vs 4.22 ± 3.97, p = 0.99). Liver BV was significantly lower for G2 versus full-dose groups (0.16 ± 0.03 vs 0.20 ± 0.05, p < 0.001). Total-body PET/CT with a half-dose [68Ga]Ga-PSMA yields image quality superior or comparable to that of conventional PET/CT. The utilization of total-body [68Ga]Ga-PSMA PET/CT meets the diagnostic demands of BCR patients, particularly those who exhibit reduced tolerance to prolonged horizontal positioning and scan durations, while simultaneously reducing radiation exposure for the subjects.

Study of prostate-specific antigen levels during salvage radiotherapy after prostate cancer surgery

BackgroundAdministration of adjuvant or salvage radiotherapy (RT) after prostate cancer (PCa) surgery is supported by clinical evidence and is a widely adopted strategy. On occasion, we detect changes in prostate-specific antigen (PSA) levels, such as a transient elevation or decline, during RT. Thus, we retrospectively investigated the frequency of changes in PSA levels, their associations with histopathological parameters, PSA doubling time (PSADT), and biochemical recurrence (BR) of PCa.MethodsThis study included 23 consecutive patients who underwent surgery for PCa between 2012 and 2019, received salvage RT without hormone therapy, and exhibited changes in PSA levels during RT. The prostatic bed was irradiated with a total dose of 64 to 66 Gy. BR was defined as consecutive PSA levels exceeding 0.2 ng/mL or having to start hormone therapy because of PSA elevation after salvage RT.ResultsDuring salvage RT after PCa surgery, PSA levels transiently increased in 11 patients (47.8%) and decreased in 12 (52.2%). When factors associated with BR were examined in patients with transient PSA elevation, seminal vesicle invasion and preoperative PSA values were identified as being statistically significant. When factors for BR were examined in patients with a decline in PSA levels, the Gleason score and PSADT were identified as being significant. Among the cases of a decline in PSA levels during salvage RT, those who received a radiation dose of less than 36 Gy did not experience BR. Similarly, patients who exhibited changes in PSA levels during salvage RT and did not have perineural invasion did not experience BR.ConclusionThis is the first study to examine the histopathological factors possibly affecting BR in patients undergoing salvage RT after PCa surgery. The results indicate that in patients with transient PSA elevation, seminal vesicle invasion is a significant risk factor. On the other hand, in patients with a decline in PSA levels during irradiation, the Gleason score and perineural invasion were found to be potential risk factors for BR. These findings suggest that a thorough examination of postoperative histopathological results may be necessary for the optimal management of patients with PCa.

Machine Learning for the Prediction of Biochemical Recurrence in Patients Treated with Radical Prostatectomy.

Biochemical recurrence (BCR) occurs in about 40% of patients with prostate cancer following radical prostatectomy (RP). Our goal was to develop a machine learning model for the prediction of BCR five-years after RP, to improve patient prognostication. Patients treated with RP at a tertiary care medical center between 1990 and 2017 were included. A gradient boosted decision trees-based machine learning model modified to handle survival data was trained on 80% of the dataset. The model's performance was evaluated on the remaining 20%. Input variables were age at surgery, prostate specific antigen (PSA) at diagnosis (in ng/mL), pathologic Gleason grade group (GG), pathologic T stage (organ confined disease vs. extracapsular extension (ECE) vs. seminal vesicle invasion (SVI)), lymph node involvement, and surgical margin status. Model performance was assessed using time-dependent area under curve of the receiver operator curve (AUC). The full dataset included 11,139 patients, of whom 1,153 (10%) developed BCR. Median age at surgery was 59 and PSA at diagnosis was 5.4 ng/mL. Only 1,080 (9.7%) patients had GG 3, and 707 (6.3%) GG 4 and 5. 1,366 (12%) patients had positive surgical margins and 134 (1.2%) had lymph node involvement. Most patients had organ confined disease with EPE and SVI diagnosed in 2,759 (25%) and 392 (3.5%) patients, respectively. Median follow-up was 5 years and median time to BCR was 4 years. When validated on the hold-out set of 2,228 patients, the model shows a time-dependent AUC of 0.82 (95% CI 0.78 - 0.86) for BCR at t = 5 years. Our machine learning model can be used to estimate risk of BCR following RP and shows exceptional performance, with implications on patient prognostication and follow-up. We are currently working on validating its performance on an external dataset.

Predictors of PSMA PET Positivity: Analysis in a Selected Cohort of Biochemical Recurrence Prostate Cancer Patients after Radical Prostatectomy.

Localized prostate cancer (PCa) can be treated with radical prostatectomy (RP). Up to 30% of patients undergoing this procedure experience biochemical recurrence (BCR), namely the rise in serum prostate-specific antigen (PSA) levels during the post-surgical follow-up, requiring further treatments and with the risk of severe disease progression. Currently, the most accurate imaging technique to confirm, detect, and locate disease relapses in BCR patients is prostate-specific membrane antigen (PSMA)-targeted PET, as recommended by international clinical guidelines. The aim of the study was to investigate potential clinical and pathological predictors of PSMA PET positivity, validated by clinical and instrumental follow-up or histopathological data. In this study, a selected cohort of BCR patients after RP and no other PCa-related therapy who underwent either PSMA PET/CT or PSMA PET/MRI has been analysed. Among the considered predictors, both pathological staging after RP equal or higher than pT3a and higher PSA levels at the time of the scan were significantly correlated with PSMA PET positivity on multivariate logistic regression analysis. As expected, PSMA PET confirmed its role as an accurate imaging technique in the setting of BCR in PCa. These findings may inform appropriate and tailored patient selection and scan timing to optimize and fully exploit this powerful diagnostic tool.

Biochemical recurrence in patients with prostate cancer after primary definitive therapy: treatment based on risk stratification.

Nearly one-third of patients with prostate cancer (PCa) experience biochemical recurrence (BCR) after primary definitive treatment. BCR increases the risk of distant metastasis and mortality in patients with prognostically unfavorable features. These patients are best managed with a tailored treatment strategy incorporating risk stratification using clinicopathological factors, next-generation imaging, and genomic testing. This narrative review examines the utility of risk stratification for the management of patients with BCR in the context of clinical trial data, referencing the latest recommendations by European and US medical societies. PubMed was searched for relevant studies published through May 21 2023 on treatment of patients with BCR after radical prostatectomy (RP) or external beam radiotherapy (EBRT). European and US guidelines support the risk-stratified management of BCR. Post-RP, salvage EBRT (with or without androgen deprivation therapy [ADT]) is an accepted treatment option for patients with BCR. Post-EBRT, local salvage therapies (RP, cryotherapy, high-intensity focused ultrasound, stereotactic body radiotherapy, and low-dose-rate and high-dose-rate brachytherapy) have demonstrated comparable relapse-free survival rates but differing adverse event profiles, short and long term. Local salvage therapies should be used for local-only relapses while ADT should be considered for regional or distant relapses. In practice, patients often receive ADT, with varying guidance for intermittent ADT vs. continuous ADT, due to consideration of quality-of-life effects. Despite a lack of consensus for BCR treatment among guideline associations and medical societies, risk stratification of patients is essential for personalized treatment approaches, as it allows for an informed selection of therapeutic strategies and estimation of adverse events. In lower-risk disease, observation is recommended while in higher-risk disease, after failed repeat local therapy, ADT and/or clinical trial enrollment may be appropriate. Results from ongoing clinical studies of patients with BCR should provide consensus for management.

Pretest PSA and Restaging PSMA PET/CT Predict Survival in Biochemically Recurrent Prostate Cancer.

A biochemical recurrence (BCR) risk model was created based on pretest prostate specific antigen (PSA) and groupings by restaging prostate specific membrane antigen (PSMA) PET/CT. A cohort of 1216 BCR patients were analyzed for overall survival (OS) according to the PSA threshold and restaging PSMA PET/CT. A Cox regression analysis of OS was carried out to detect significant clinical characteristics. In the cohort, 271 patients had a pretest PSA of <0.5 ng/mL and 945 patients had higher PSA values. The restaging PSMA PET/CT was positive for 834 patients and negative for 369. Of 1203 patients, 133 (11%) died, including 19 of the 369 (5%) patients without positive sites on the restaging PSMA PET/CT, 82 of the 711 (12%) with 1-5 positive sites, and 32 of the 123 (26%) with >5 positive sites. In the Cox regression analysis, four variables significantly predicted OS: treatment center, International Society of Urologic Pathology (ISUP) grade, pretest PSA threshold, and the grouping of positive sites on the restaging PSMA PET/CT. The pretest PSA and PSMA PET/CT were important for the OS of the BCR patients. The findings argue for the new BCR risk model and serve as framework for ongoing trials.