Biochemical Recurrence Of Prostate Cancer Research Articles

Identification and validation of an individualized metabolic prognostic signature for predicting the biochemical recurrence of prostate cancer based on the immune microenvironment

BackgroundProstate cancer (PCa) is the most prevalent genitourinary malignancy in men, with a significant proportion of patients developing biochemical recurrence (BCR) after treatment. The immune microenvironment and metabolic alterations have crucial implications for the tumorigenesis and progression of PCa. Therefore, identifying metabolic genes associated with the immune microenvironment holds promise for predicting BCR and improving PCa prognosis.MethodsIn this study, ssGSEA and hierarchical clustering analysis were first conducted to evaluate and group PCa samples, followed by the use of the ESTIMATE and CIBERSORT algorithms to characterize the immunophenotypes and tumor microenvironment. The differential metabolic genes (MTGs) between groups were utilized to develop a prognostic-related signature. The predictive performance of the signature was assessed by principal component analysis (PCA), receiver operating characteristic (ROC) curve analysis, survival analysis, and the TIDE algorithm. A miRNA-MTGs regulatory network and predictive nomogram were constructed. Moreover, the expression of prognostic MTGs in PCa was detected by RT‒qPCR.ResultsPCa samples from the TCGA cohort were separated into two groups: the immune-low group and immune-high group. Forty-eight differentially expressed MTGs between the groups were identified, including 37 up-regulated and 11 down-regulated MTGs. Subsequently, CEL, CYP3A4, and PDE6G were identified as the genes most strongly associated with the BCR of PCa patients and these genes were utilized to establish the MTGs-based prognostic signatures. PCA, ROC curves analysis, Kaplan–Meier survival analysis, and the nomogram all showed the good predictive ability of the signature regardless of clinical variables. Furthermore, the MTGs-based signature was indicated as a potential predictive biomarker for immunotherapy response. Nine miRNAs involved in the regulation of prognostic MTGs were determined. In addition to the CEL gene, the PDE6G and CYP3A4 genes were expressed at higher levels in PCa samples.ConclusionsThe MTGs-based signature represents a novel approach with promising potential for predicting BCR in PCa patients.

Updates on Management of Biochemical Recurrent Prostate Cancer.

Patients with biochemical recurrent prostate cancer (BCR) are a heterogeneous group, whereby a personalized approach to management is critical. Patients with high-risk features such as PSA doubling time (PSADT) ≤ 9-12 months warrant earlier imaging for metastasis detection and consideration for intensified therapy (beyond intermittent androgen deprivation alone) during this phase of BCR-only disease. The BCR phase represents a unique opportunity to impact disease survival and delay metastasis progression. There is compelling evidence from the EMBARK trial that ADT monotherapy is no longer the optimal consideration for high-risk BCR patients.

Diagnostic accuracy of bone scan at different PSA levels in biochemical recurrence of prostate cancer

ObjectiveTo determine the diagnostic accuracy of Bone Scan at different PSA levels for detecting skeletal metastases in men with biochemical recurrence of prostate cancer. MethodsWe conducted a retrospective review of the statewide RIS-PACS to identify 251 men with biochemical recurrence who underwent both a Bone Scan and Ga68 PSMA PET/CT (within 2 months of each other) between September 2019 and December 2022 at a single institution. The Ga68 PSMA PET/CT report was considered to be the reference standard. ResultsThe median age was 72 years (IQR 67–76) with a median PSA level of 1 ng/ml (IQR 0.25–2.8). Using Ga68 PSMA PET/CT as the reference standard, 68/251 patients (25%) were positive for osseus metastases. Overall sensitivity and specificity of Bone Scan was 51% (95% CI 40–64%) and 99% (95% CI 98–100%) respectively. Using PSA banding, a PSA threshold of 20 ng/ml provided the greatest discriminatory benefit with sensitivity of the Bone Scan below the threshold being 46% (95% CI 33–59%) and above the threshold being 89% (95% CI 68–100%). Specificity remained consistently high both below and above this threshold. ConclusionBone Scan provides greater diagnostic accuracy for detecting skeletal metastases in biochemical recurrence when the PSA level is above 20 ng/ml. This knowledge is valuable in optimising imaging algorithms in biochemical recurrence, particularly in regions where PSMA PET/CT is less readily available or affordable.

ACOX2 Serves as a Favorable Indicator Related to Lipid Metabolism and Oxidative Stress for Biochemical Recurrence in Prostate Cancer.

Given the heterogeneity of tumors, there is an urgent need for accurate prognostic parameters in prostate cancer (PCa) patients. Lipid metabolism (LM) reprogramming and oxidative stress (OS) play a vital role in the progression of PCa. In this work, we identified five LM-OS-related genes (including ACOX2, PPRAGC1A, PTGS1, PTGS2, and HAO1) associated with the biochemical recurrence (BCR) of PCa. Subsequently, a prognostic signature was established based on these five genes. Kaplan-Meier survival estimates, receiver operating characteristic curves, and relationship analysis between risk score and clinical characters were applied to measure the robustness of the signature in an external cohort. A nomogram of risk score combined with clinical characteristics was constructed for clinical application. Functional enrichment analysis suggested that the underlying mechanism related to the signature included the calcium signaling, lipid transport, and cell cycle signaling pathways. Furthermore, WEE1 inhibitor was identified as a potential agent related to the cell cycle for high-risk patients. The mRNA expression and the prognostic value of the five genes were determined, and ACOX2 was identified as the key gene related to the prognostic signature. The protein expression of ACOX2 was measured in a prostate tissue microarray through an immunohistochemistry assay, confirming the bioinformatics results. By constructing the ACOX2-overexpressing PCa cell lines PC-3 and 22Rv1, the biological function of PCa cells was investigated. The cell viability, colony formation, migration, and invasion ability of PCa cell lines overexpressing ACOX2 were hindered. Decreased cellular lipid content and elevated cellular ROS content were observed in ACOX2-overexpressing PCa cell lines with reduced G2/M phases. In conclusion, this work presents the first prognostic signature specifically focused on LM-OS for PCa. ACOX2 could serve as a favorable indicator for the BCR in PCa. Further experiments are required to identify the potential underlying mechanism.

Bi-Parametric Magnetic Resonance Imaging Analysis of Biochemical Recurrence of Prostate Cancer after Radical Surgery and Its Predictive Value: A Retrospective Study.

This study aimed to analyse the characteristics of biochemical recurrence after radical prostatectomy via bi-parametric magnetic resonance imaging. A total of 200 patients with radical prostatectomy admitted to our hospital from January 2016 to January 2021 were retrospectively enrolled as observation objects. According to whether there was biochemical recurrence after surgery, the patients were divided into the abnormal group (n = 62) and normal group (n = 138). Clinical data, encapsulation infiltration, seminal vesicle infiltration and prostate imaging report and data system (PI-RADS) were collected and compared between the two groups. Propensity score matching (PSM) was used to balance the baseline data of the two groups. Student's t-test and Chi-square test were used to analyse the data. PSM was performed in a 1:1 ratio, and a total of 72 patients were included in the abnormal and normal groups. The baseline data of the patients in each group were not statistically significant. The incidence of extraperitoneal invasion and seminal vesicle invasion was higher in the abnormal group than in the normal group, and we observed a significant difference in PI-RADS scores between the two groups (p < 0.05). Extracapsular invasion, seminal vesicle invasion, PI-RADS score and biochemical recurrence were significantly correlated (p < 0.05). The PI-RADS score has a high value for predicting biochemical recurrence, with an area under the curve value of 0.824, sensitivity of 0.667, specificity of 0.861 and Youden index of 0.528. Bi-parametric magnetic resonance imaging has a high predictive value in biochemical recurrence after radical prostatectomy, which can provide reference for early intervention measures.

Quantification of collagen content and stromal cellularity within reactive stroma is predictive of prostate cancer biochemical recurrence and specific death

Semiquantitative reactive stromal grading has been shown to be a predictor of biochemical recurrence and prostate cancer (PCa) specific death. It has been extensively validated. In this study we tested novel technologies to introduce quantitative measures of host response, in particular collagen content and stromal cellularity. We use 3 large retrospective cohorts, the Baylor College of Medicine cohort, the Brady cohort and the Pound cohort. Slides were stained and digitized using image deconvolution and analyzed using image segmentation and image analyses. PicroSirius red stain histochemical stains were used for collagen quantification. Area of cancer and stroma were measured independently, without regard to quality of stroma. Cellularity, in each compartment, was measured using image deconvolution, image segmentation and image analysis. Two biomarkers were tested in 3 independent cohorts with two endpoints, biochemical recurrence and prostate cancer specific death. Stromal cellularity (qCollCell) and stromal collagen area (qCollArea) are independently predictive biochemical recurrence in the Hopkins Brady cohort, particularly in Gleason 6–7 patients. Multivariate analysis demonstrated that increased stroma cellularity (qCollCell) was a significant predictor of PCa specific death, when compared to an established model of PCa, in the Baylor cohort. Stromal collagen (qCollArea) independently predicts PCa-specific death in the Hopkins Pound cohort. The introduction of a computerized quantitative test of the host response increases the probability that this test will be reproducible in other cohorts. The ability to improve prediction of prostate cancer specific death might lie in the study of the host and its response.

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.

Metalloproteinase 9 immunostaining profile is positively correlated with tumor grade, extraprostatic extension and biochemical recurrence in prostate cancer

Metastasis is the main problem in the treatment of prostate cancer (PCa), and for it to occur, proteolytic enzymes must remodel the extracellular matrix (ECM) surrounding the tumor. The most important group of enzymes with this action include the matrix metalloproteinases (MMPs), which act on various substrates cleaving ECM components. The present study aimed to evaluate the protein immunostaining profiles of matrix metalloproteinase 2 (MMP-2) and 9 (MMP-9) in PCa Brazilian patients using the indirect immunohistochemical methodology. The tissue samples (n = 178), 60 from malignant tumor, 58 from adjacent non-tumor, and 60 from ECM, were evaluated according to the immunostaining intensity. The malignant tumor cytoplasmic MMP-2 immunostaining was more intense than in ECM (p = 0.001), but it did not correlate with any clinical-pathological parameter. The MMP-9 staining was similar in tumor cytoplasm, adjacent non-tumor cytoplasm and ECM, but showed significant positive correlations with ISUP grade (p = 0.044; Tau=0.249), extraprostatic extension (p = 0.025; Tau=0.309), and biochemical recurrence (p = 0.048; Tau=0.306). A significant positive correlation was also observed between MMP-2 and MMP-9 in all cell compartments analyzed. Although further research is warranted to elucidate the precise mechanisms underlying these observations, our findings suggest MMP-9 as a promising candidate marker for tissue invasion that could be used in predicting the progression and prognosis of PCa.

Association of PSMA PET-derived Parameters and Outcomes of Patients Treated for Oligorecurrent Prostate Cancer.

Background Prostate-specific membrane antigen (PSMA) PET is useful in the early detection of oligorecurrent prostate cancer (PCa), but whether PSMA PET parameters can be used to identify patients who would benefit from metastasis-directed therapy (MDT) with radiation or surgery remains uncertain. Purpose To assess the association of PSMA PET parameters with outcomes of patients with oligorecurrent PCa after MDT. Materials and Methods In this retrospective analysis of a single-center phase II trial that enrolled patients with biochemical recurrence of PCa after maximal local therapy and with no evidence of disease at conventional imaging, patients underwent PSMA PET (between May 2017 and November 2021), and unveiled recurrences were treated with MDT. Maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean) and PSMA tumor volume derived using thresholds of 2.5 (SUVmean2.5) and 41% (SUVmean41%), respectively, were recorded for sites of recurrence on PSMA PET scans, and a molecular imaging PSMA score was assigned. These parameters were also corrected for smooth filter and partial volume effects, and the PSMA score was reassigned. Cox proportional hazards models were used to evaluate the relationship between PSMA PET parameters and outcomes. Results A total of 74 men (mean age, 68.3 years ± 6.6 [SD]) with biochemical recurrence of PCa were included. PSMA PET revealed 145 lesions in the entire cohort, of which 125 (86%) were metastatic lymph nodes. Application of the correction factor changed the PSMA score in 88 of 145 lesions (61%). Mean SUVmax, SUVmean2.5, and SUVmean41% were associated with lower risk of biochemical progression (hazard ratio [HR] range, 0.77-0.95; 95% CI: 0.61, 1.00; P = .03 to P = .04). For corrected parameters, mean SUVmax, mean SUVmean2.5, mean SUVmean41%, mean PSMA score, maximum SUVmean2.5, maximum SUVmean41%, and maximum PSMA score were associated with a lower risk of biochemical progression (HR, 0.61-0.98; 95% CI: 0.39, 1.00; P = .01 to P = .04). Conclusion Measured and corrected PSMA PET parameters were associated with biochemical progression in men with oligorecurrent PCa treated with MDT. Clinical trial registration no. NCT03160794 © RSNA, 2023 See also the editorial by Civelek in this issue.

Recurrent prostate cancer: combined role for MRI and PSMA-PET in 68Ga-PSMA-11 PET/MRI

ObjectivesTo investigate the specific strengths of MRI and PET components in 68Ga-PSMA-11 PET/MRI for staging of patients with biochemically recurrent prostate cancer (PCa).MethodsPatients with biochemical recurrence of PCa and contrast-enhanced whole-body 68Ga-PSMA-11 PET/MRI including a dedicated pelvic multiparametric MRI were included in this retrospective study. Imaging datasets of MRI and PET were evaluated separately regarding local PCa recurrence (Tr), pelvic lymph node metastases (N1), distant lymph node metastases (M1a), bone metastases (M1b), and soft tissue metastases (M1c) according to PROMISE version 1. Data evaluation was performed patient- and region-/lesion-based. Cox regression revealed a PSA of 1.69 ng/mL as a cut-off for subgroup analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were evaluated for each image component. Differences in staging accuracy were assessed using the Wilcoxon and McNemar test.ResultsAltogether 102 patients (mean aged 68 ± 8 years, median PSA 1.33 ng/mL) were included. PCa was found in 70/102 (68%) patients. Accuracy of MRI in the detection of Tr, N1, M + , M1a, and M1b was 100%, 79%, 90%, 97%, and 95% for PSA < 1.69 ng/mL and 100%, 87%, 87%, 91%, and 96% for PSA > 1.69 ng/mL. Accuracy of 68Ga-PSMA-11 PET was 93%, 97%, 93%, 98%, and 100% for PSA < 1.69 ng/mL and 87%, 91%, 96%, 100%, and 96% for PSA > 1.69 ng/mL.ConclusionsCombined assessment of 68Ga-PSMA-11 PET/MRI improves tumor localization in men with biochemical recurrence. The MRI detected local recurrence of PCa more often whereas 68 Ga-PSMA-11 PET detected lymph node metastases more often, especially for PSA < 1.69 ng/mL.Clinical relevance statementThis study gives a scientific baseline to improve the understanding and reading of 68Ga-PSMA-11 PET/MRI imaging in patients with biochemically recurrent PCa by showing the specific strength of each imaging component.Key Points• Combining the individual modality strengths of 68Ga-PSMA-11 PET/MRI improves tumor localization in men with biochemical recurrence of prostate cancer.• MRI component of 68 Ga-PSMA-11 PET/MRI shows its strength in detecting local recurrence of prostate cancer, especially at PSA < 1.69 ng/mL.• 68 Ga-PSMA-11 PET component shows its strength in detecting local and distant lymph node metastases, especially at PSA < 1.69 ng/mL.

MRI and PSMA PET/CT of Biochemical Recurrence of Prostate Cancer.

Prostate cancer may recur several years after definitive treatment, such as prostatectomy or radiation therapy. A rise in serum prostate-specific antigen (PSA) level is the first sign of disease recurrence, and this is termed biochemical recurrence. Patients with biochemical recurrence have worse survival outcomes. Radiologic localization of recurrent disease helps in directing patient management, which may vary from active surveillance to salvage radiation therapy, androgen-deprivation therapy, or other forms of systemic and local therapy. The likelihood of detecting the site of recurrence increases with higher serum PSA level. MRI provides optimal diagnostic performance for evaluation of the prostatectomy bed. Prostate-specific membrane antigen (PSMA) PET radiotracers currently approved by the U.S. Food and Drug Administration demonstrate physiologic urinary excretion, which can obscure recurrence at the vesicourethral junction. However, MRI and PSMA PET/CT have comparable diagnostic performance for evaluation of local recurrence after external-beam radiation therapy or brachytherapy. PSMA PET/CT outperforms MRI in identifying recurrence involving the lymph nodes and bones. Caveats for use of both PSMA PET/CT and MRI do exist and may cause false-positive or false-negative results. Hence, these techniques have complementary roles and should be interpreted in conjunction with each other, taking the patient history and results of any additional prior imaging studies into account. Novel PSMA agents at various stages of investigation are being developed, and preliminary data show promising results; these agents may revolutionize the landscape of prostate cancer recurrence imaging in the future. ©RSNA, 2023 Quiz questions for this article are available through the Online Learning Center. See the invited commentary by Turkbey in this issue. The slide presentation from the RSNA Annual Meeting is available for this article.

Integration of Multiparameter MRI into Conventional Pretreatment Risk Factors to Predict Positive Surgical Margins After Radical Prostatectomy

Introduction/BackgroundPositive surgical margins (PSMs) after radical prostatectomy (RP) can increase the risk of biochemical recurrence in prostate cancer (PCa) patients. However, the prediction of the likelihood of PSMs in patients undergoing similar surgical procedures remains a challenge. We aim to develop a predictive model for PSMs in patients undergoing non–nerve-sparing RP. Patients and MethodsIn this retrospective study, we analyzed data from PCa patients who underwent minimally invasive non–nerve-sparing RP at our hospital between June 2017 and June 2021. We identified independent risk factors associated with PSMs using clinical and MRI-based parameters in univariate and multivariate logistic regression analyzes. These factors were then used to develop a nomogram for predicting the probability of PSMs. The predictive performance was validated using calibration and receiver operating characteristic curve, area under the curve ,and decision curve analysis. ResultsMultivariate analyzes revealed prostate-specific antigen density, tumor size, tumor location at the apex, tumor contact length, extracapsular extension (ECE) level, and apparent diffusion coefficient value as independent risk factors. A nomogram was developed and validated with high accuracy (C-index = 0.78). Furthermore, we found that 44.2% of patients diagnosed with organ-confined disease had ECE after surgery, and 29.1% of patients with Gleason scores ≤7 had higher pathological scores. Interestingly, the tumor burden calculated from PCa biopsy cores was overestimated when compared to postoperative PCa specimens. ConclusionWe developed a reliable nomogram for predicting the risk of PSMs in PCa patients undergoing non–nerve-sparing RP. The study highlights the importance of incorporating these parameters in personalized surgical management.

Development and validation of a circulating tumor cells-related signature focusing on biochemical recurrence and immunotherapy response in prostate cancer

BackgroundStudies have shown that the circulating tumor cells (CTCs) play a key role for invasion and formation of distant metastases in prostate cancer (PCa). However, few CTCs-related genes (CRGs) have been developed for biochemical recurrence (BCR) prediction and clinical applications of PCa patients. Materials and methodsBioinformatics analysis with public PCa datasets were used to investigate the relationship between the differentially expressed CRGs and BCR. Lasso-COX regression analysis was used to constructed and validated a CRGs-based BCR prediction signature for PCa. Single-cell data were used to validate the expression levels of signature genes in different cell types and then explored the cell-cell communication relationships. Finally, the expression levels of signature genes were verified and the CRGs involved in immunotherapy response were further identified. ResultsThirteen CRGs were differentially expressed and closely associated with BCR in PCa. Then we constructed and validated a BCR prediction signature for PCa patients based on 3 differentially expressed CRGs (EMID1, SPP1 and UBE2C), and the signature was an independent factor to predict BCR for PCa. Single-cell data showed the specific expression patterns of the signature genes, while the SPP1 pathway plays an important role in cell-cell communication. Further analyses suggested UBE2C was highly expressed in BCR group and high expression of UBE2C had a better response for patients who received immunotherapy. Moreover, the expression levels of UBE2C in CTCs were higher than other cells and tissues, indicated that UBE2C may affect the BCR event of PCa patients through CTCs. ConclusionOur findings demonstrated that CRGs were significantly associated with BCR and immunotherapy efficacy in PCa and CRGs may influence the BCR event through CTCs.

MYB exhibits racially disparate expression, clinicopathologic association, and predictive potential for biochemical recurrence in prostate cancer

MYB acts as a potentiator of aggressiveness and castration resistance in prostate cancer (PCa) through aberrant activation of androgen receptor (AR) signaling. Since Black men experience higher PCa incidence and mortality than White men, we examined if MYB was differentially expressed in prostate tumors from patients of these racial backgrounds. The data reveal that aberrant MYB expression starts early in precancerous high-grade prostate intraepithelial neoplastic lesions and increases progressively in malignant cells. PCa tissues from Black patients exhibit higher MYB expression than White patients in overall and grade-wise comparisons. MYB also exhibits a positive correlation with AR expression and both display higher expression in advanced tumor stages. Notably, we find that MYB is a better predictor of biochemical recurrence than AR, pre-treatment PSA, or Gleason's grades. These findings establish MYB as a promising molecular target in PCa that could be used for improved risk prediction and therapeutic planning.

National Long-term Survival Estimates After Radical Prostatectomy for Prostate Cancer

ObjectiveTo examine survival and disease control outcomes, including metastasis-related survival outcomes, in a large contemporary cohort of patients undergoing radical prostatectomy for localized prostate cancer. MethodsWe conducted a retrospective study of men with localized prostate cancer treated with radical prostatectomy from 2005-2015 with follow up through 2019 in the Veterans Health Administration. We defined biochemical recurrence (BCR) as a PSA ≥0.2 ng/mL. We used a validated natural language processing encoded dataset to identify incident metastatic prostate cancer. We estimated overall survival from time of surgery, time of BCR, and time of first metastasis using the Kaplan-Meier method. We then estimated time from surgery to BCR, BCR to metastatic disease, and prostate-cancer specific survival from various time points using cumulative incidence considering competing risk of death. ResultsOf 21,992 men undergoing radical prostatectomy, we identified 5,951 (27%) who developed biochemical recurrence (BCR). Of men with BCR, 677 (11%) developed metastases. We estimated the 10-year cumulative incidence of BCR and metastases after BCR were 28% and 20%, respectively. Median overall survival after BCR was 14 years, with 10-year survival of 70%. From the time of metastasis, median overall survival approached 7 years, with 10-year overall survival of 34%. Prostate cancer-specific survival for the entire cohort at 10 years was 94%. ConclusionsIn this large contemporary national cohort, survival for men with biochemically-recurrent prostate cancer is longer than historical cohorts. When counseling patients and designing clinical studies, these updated estimates may serve as more reliable reflections of current outcomes.

Multiparametric MRI-based 5-year Risk Prediction Model for Biochemical Recurrence of Prostate Cancer after Radical Prostatectomy.

Background Current predictive tools to estimate the risk of biochemical recurrence (BCR) after treatment of prostate cancer do not consider multiparametric MRI (mpMRI) information. Purpose To develop a risk prediction tool that considers mpMRI findings to assess the risk of 5-year BCR after radical prostatectomy. Materials and Methods In this retrospective single-center analysis in 1459 patients with prostate cancer who underwent mpMRI before radical prostatectomy (in 2012-2015), the outcome of interest was 5-year BCR (two consecutive prostate-specific antigen [PSA] levels > 0.2 ng/mL [0.2 µg/L]). Patients were randomly divided into training (70%) and test (30%) sets. Kaplan-Meier plots were applied to the training set to estimate survival probabilities. Multivariable Cox regression models were used to test the relationship between BCR and different sets of exploratory variables. The C-index of the final model was calculated for the training and test sets and was compared with European Association of Urology, University of California San Francisco Cancer of the Prostate Risk Assessment, Memorial Sloan-Kettering Cancer Center, and Partin risk tools using the partial likelihood ratio test. Five risk categories were created. Results The median duration of follow-up in the whole cohort was 59 months (IQR, 32-81 months); 376 of 1459 (25.8%) patients had BCR. A multivariable Cox regression model (referred to as PIPEN, and composed of PSA density, International Society of Urological Pathology grade group, Prostate Imaging Reporting and Data System category, European Society of Urogenital Radiology extraprostatic extension score, nodes) fitted to the training data yielded a C-index of 0.74, superior to that of other predictive tools (C-index 0.70 for all models; P ≤ .01) and a median higher C-index on 500 test set replications (C-index, 0.73). Five PIPEN risk categories were identified with 5-year BCR-free survival rates of 92%, 84%, 71%, 56%, and 26% in very low-, low-, intermediate-, high-, and very high-risk patients, respectively (all P < .001). Conclusion A five-item model for predicting the risk of 5-year BCR after radical prostatectomy for prostate cancer was developed and internally verified, and five risk categories were identified. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Aguirre and Ortegón in this issue.

Enzalutamide and Quality of Life in Biochemically Recurrent Prostate Cancer

BackgroundEMBARK, a controlled trial reported elsewhere, showed enzalutamide plus leuprolide (combination) and enzalutamide monotherapy prolonged metastasis-free survival versus placebo plus leuprolide (alone) in patients with high-risk biochemically recurrent prostate cancer. Health-related quality of life was also analyzed but not reported.MethodsIn EMBARK, patients with biochemical recurrence (prostate-specific antigen doubling time of ≤9 months) were randomly assigned (1:1:1) to combination (n=355), leuprolide-alone (n=358), or enzalutamide monotherapy (n=355). In this article we provide the patient-reported outcomes (PROs) from EMBARK at baseline and every 12 weeks until metastasis or death. The key end point was time to first and confirmed clinically meaningful deterioration (TTFD/TTCD) in pain and health-related quality of life using four PRO measures and predefined thresholds.ResultsAt baseline, all groups had high health-related quality of life. For worst pain, the median TTFD was 19.35 months with leuprolide alone, 13.93 months with combination (hazard ratio, 1.08; 95% confidence interval [CI], 0.89 to 1.30) and 16.59 months with monotherapy (hazard ratio, 1.09; 95% CI, 0.90 to 1.31). The median TTCD was 66.27 months with leuprolide alone, 80.00 months with combination (hazard ratio, 0.82; 95% CI, 0.65 to 1.04), and 60.91 months with monotherapy (hazard ratio, 1.02; 95% CI, 0.82 to 1.28). For Functional Assessment of Cancer Therapy–Prostate total score, the median TTFD was 11.10 months with leuprolide alone, 8.31 months with combination (hazard ratio, 1.14; 95% CI, 0.95 to 1.36), and 8.38 months with monotherapy (hazard ratio, 1.17; 95% CI, 0.98 to 1.39). The median TTCD was 36.53 months with leuprolide alone, 38.77 months with combination (hazard ratio, 1.04; 95% CI, 0.85 to 1.28), and 30.55 months with monotherapy (hazard ratio, 1.16; 95% CI, 0.95 to 1.41).ConclusionsThe PROs from EMBARK show that both enzalutamide combination and monotherapy versus leuprolide alone, with oncologic benefits noted above, preserved high health-related quality of life in patients with high-risk biochemical recurrence of prostate cancer. (Funded by Pfizer and Astellas Pharma; ClinicalTrials.gov number, NCT02319837.)

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.

Quantitative [68Ga]Ga-PSMA-11 PET biomarkers for the analysis of lesion-level progression in biochemically recurrent prostate cancer: a multicentre study

[68Ga]Ga-PSMA-11 PET has become the standard imaging modality for biochemically recurrent (BCR) prostate cancer (PCa). However, its prognostic value in assessing response at this stage remains uncertain. The study aimed to assess the prognostic significance of radiographic patient-level patterns of progression derived from lesion-level biomarker quantitation in metastatic disease sites. A total of 138 BCR PCa patients with both baseline and follow-up [68Ga]Ga-PSMA-11 PET scans were included in this analysis. Tumour response was quantified at the lesion level using commonly used quantitative parameters (SUVmean, SUVmax, SUVpeak, volume), and patients were classified as systemic, mixed, or no-progression based on these response classifications. A total of 328 matched lesions between baseline and follow-up scans were analysed. The results showed that systemic progressors had a significantly higher risk of death than patients with no progression with SUVmean demonstrating the highest prognostic value (HR = 5.70, 95% CI = 2.63–12.37, p < 0.001, C-Index = 0.69). Moreover, progressive disease as measured by SUVmean using the radiographic PSMA PET Progression Criteria (rPPP) was found to be significantly prognostic for patient overall survival (HR = 3.67, 95% CI = 1.82–7.39, p < 0.001, C-Index = 0.65). This work provides important evidence supporting the prognostic utility of PSMA response quantitation in the BCR setting.

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.