PSA Doubling Time Research Articles

Development and validation of prognostic model for metastatic castration-resistant prostate cancer patients treated with first-line abiraterone or enzalutamide.

IntroductionOver the years, several prognostic models were developed in patients receiving chemotherapy for metastatic castration resistant prostate cancer (mCRPC), while data on androgen-receptor signaling inhibitors (ARSI) in a real-world setting are limited. Patients and methodsWe compared a consecutive series of 565 mCRPC patients receiving first-line ARSI at four high-volume Italian Centers (development set) to an external series of 180 patients receiving the same treatment at another Italian high-volume Center (training set), between 2011 and 2022.Sixteen clinical and baseline laboratory variables were selected to develop a prognostic model. Patients were categorized into risk groups according to the number of independent factors positively associated with overall survival (OS). ResultsIn the development cohort, after a median follow-up of 21.1 months, the median OS was 30.4 months (95% CI 27.5-33.4). At the multivariate analysis, seven variables [age, prostate specific antigen (PSA) doubling time, baseline levels of hemoglobin, PSA, time to castration resistance, ECOG PS and bone metastases number) were included into the final model.The median OS was 13.4, 25.7 and 46.4 months in poor (0-2 factors), intermediate (3-4 factors) and good (≥5 factors) prognosis group, respectively.The application of the model to the validation set confirmed its ability to prognosticate for OS. The model c-indexes were 0.68 (95% CI 0.64-0.72) and 0.75 (95% CI 0.68–0.81) in the development and validation cohort, respectively. ConclusionsOur model, based on clinical and laboratory variables readily assessable in clinical practice, might prognosticate the OS of mCRPC patients receiving first-line ARSI. Micro AbstractA retrospective study comparing a development to a validation cohort of mCRPC patients receiving ARSI found a new prognostic model. It included seven clinical and baseline laboratory variables and confirmed its ability to prognosticate for OS.

Nodal radiotherapy for prostate adenocarcinoma recurrence: predictive factors for efficacy.

Nodes are the second site for prostate cancer recurrence. Whole-pelvic radiotherapy (WPRT) has shown superiority over nodal stereotactic body radiotherapy (SBRT) in two retrospective cohorts. We aimed to compare both modalities and assess factors associated with treatment outcomes. This retrospective multicentric cohort study included patients from five institutions spanning from 2010 to 2022. Patients had a history of prostatic adenocarcinoma classified as N0 M0 at diagnosis with a first nodal-only pelvic castration-sensitive recurrence. Failure-free survival (FFS) was defined as the time from the end of RT to the first failure event-biochemical or imaging recurrence, or death. A total of 147 patients (pts) were analyzed, mainly treated for a recurrence after initial prostatectomy (87%), with 64 (43.5%) undergoing SBRT and 83 (56.5%) undergoing WPRT. SBRT was chosen mainly for dosimetric constraints (67%) and was associated with a lower rate of concomitant androgen deprivation therapy (ADT) prescription. With a median follow-up of 68 months [inter-quartile range (IQR) = 51], FFS was significantly lower in the SBRT group (p < 0.0001). In multivariable analysis, WPRT and ADT were associated with a longer FFS. Factors associated with a longer FFS after SBRT included associated ADT, lower prostate-specific antigen (PSA) levels, a PSA doubling time >6 months, and a Gleason score <8. SBRT was associated with a lower rate of genitourinary and gastrointestinal grade ≥2 complications. For an isolated pelvic nodal prostate cancer recurrence, SBRT is associated with a shorter FFS compared to WPRT. SBRT is often more convenient for patients and leaves further pelvic salvage options available, so it can be explored as an option for well-informed patients.

Optimal timing for initiating androgen receptor signaling inhibitor therapy in patients with nonmetastatic castration-resistant prostate cancer: a multicenter collaborative study.

We determined the optimal timing for initiating androgen receptor signaling inhibitor (ARSI) therapy in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) and assessed its impact on oncological outcomes. This retrospective study included 145 nmCRPC patients who received enzalutamide, apalutamide or darolutamide at the Jikei University Hospital or its affiliated institutions between May 2014 and November 2022. Patients were stratified based on prostate-specific antigen (PSA) doubling time (PSADT) at CRPC diagnosis and PSA levels at ARSI initiation. Oncological outcomes, including progression-free survival (PFS), metastasis-free survival (MFS), cancer-specific survival and overall survival, were assessed using the Kaplan-Meier curve and Cox regression analysis. The median age of the patients was 73 (interquartile range [IQR]: 52-88) years, and the median follow-up duration was 36 (IQR: 2-104) months. The median PSA level at ARSI initiation was 5.4 (IQR: 2.2-48) ng/ml, and 44.8% of patients had a PSADT <3months. Multivariate analysis revealed that PSADT and PSA levels at ARSI initiation were independent MFS predictors. Patients with a PSADT ≤3months and a PSA level≥5.4ng/ml experienced significantly reduced PFS and MFS. Notably, ARSI initiation at a PSA level ≥5.4ng/ml was associated with worse outcomes, suggesting the potential benefit of earlier intervention. Patients with rapid PSADT are at increased risk of early disease progression, suggesting that immediate treatment may be warranted. In addition, initiating therapy at a PSA level <5.4ng/ml may be associated with improved patient outcomes in patients with low PSADT.

Midlife baseline prostate-specific antigen, velocity, and doubling time association with lethal prostate cancer and mortality.

Midlife baseline prostate-specific antigen (MB PSA), defined as a single PSA value measured between 40-59 years of age, has been proposed as a tool that can limit potential harms of PSA screening. This study aimed to examine the ability of MB PSA versus PSA doubling time (PSADT) and PSA velocity (PSAV) in assessing the likelihood of developing of lethal prostate cancer (PCa) in a diverse and contemporary North American population. Men 40-59 years old, who received their first PSA between the years 1995 and 2019, were included. For MB PSA values, the first PSA test result was included. For PSADT, the first two PSA test results were included. For PSAV, the first three PSA test results within 30 months were included. Selection criteria resulted in a total of 77,594 patients with at least two PSA test results and 11,634 patients with at least three PSA test results. Multivariable Fine-Gray regression was used to examine the impact of the value of the PSA testing methods on the development of lethal PCa (defined as death from PCa or development of metastatic disease either at diagnosis or during follow-up). Time-dependent receiver operating characteristic/area under the curve (AUC) at 5, 10, and 15 years were plotted. In the main cohort, patients were most frequently in the 50-54 age category (32.8%), had a Charlson comorbidity index of 0 (70.5%), and were White (63.2%). Of these, 9.3% had the midlife baseline PSA in the top 10th percentile, and 0.4% had a PSADT 0-6 months. Lethal PCa was diagnosed in 593 (0.8%) patients. The median (interquartile range) time to lethal PCa was 8.6 (3.2-14.9) years. In the main cohort, MB PSA and PSADT showed significant associations with the occurrence of lethal PCa, with a hazard ratio (HR) of 6.10 (95% confidence interval [CI], 4.85-7.68) and HR of 2.20 (95% CI, 1.07-4.54) for patients in the top 10th percentile MB PSA group and in the PSADT between 0 to <6 months group, respectively. In patients with three PSA results available, MB PSA and PSAV showed significant associations with the occurrence of lethal PCa, with a HR of 3.95 (95% CI, 2.29-6.79) and 3.57 (95% CI, 2.17-5.86) for patients in the top 10th percentile MB PSA group and in the in the PSAV >0.4 ng/mL/year group, respectively. PSADT and PSAV did not exhibit higher AUCs than MB PSA in assessing the likelihood of lethal PCa. Specifically, they were 0.818 and 0.708 at 10 and 15 years, respectively, for the PSADT; 0.862 and 0.756 at 10 and 15 years, respectively, for the PSAV; and 0.868 and 0.762 at 10 and 15 years, respectively, for the MB PSA (all p>.05). The study findings are that PSAV or PSADT were not superior to midlife baseline in assessing the likelihood of developing lethal PCa. This suggests that these variables may not have practical use in enhancing PSA screening strategies in a clinical setting.

Prognostic Outcomes and Predictive Factors in Non-Metastatic Castration-Resistant Prostate Cancer Patients Not Treated with Second-Generation Antiandrogens.

Background/Objectives: Patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and high-risk features frequently have progression to life-threatening metastasis without second-generation antiandrogens. This study investigated nmCRPC patients for the survival and prognostic factors from a cohort before the approved use of second-generation antiandrogens. Methods: From March 2016 to January 2021, 326 patients treated with second-generation antiandrogens for metastatic castration-resistant prostate cancer (mCRPC) or metastatic castration-sensitive prostate cancer were retrieved. Forty-four patients experiencing nmCRPC with no use of second-generation antiandrogens were reviewed. The prognostic factors, at initial diagnosis or at nmCRPC, associated with metastasis-free survival (MFS) and overall survival (OS) were analyzed. Results: The median follow-up time after nmCRPC was 46 months. The median PSA level at nmCRPC was 2.7 ng/mL. Thirty-eight of forty-four patients with nmCRPC had a PSA doubling time (PSADT) of 10 months or shorter, and the median PSADT was 4 months. The median OS from nmCRPC was 53 months, and the median interval for nmCRPC patients progressing to mCRPC was 20 months. Upon univariate analysis, PSADT < 10 months (p = 0.049) and the very-high-risk group at the initial diagnosis (p = 0.043) were associated with significantly shorter post-nmCRPC MFS. The very-high-risk group (p = 0.031) was associated with significantly worse post-nmCRPC OS. In terms of survivals from the initial diagnosis of prostate cancer, Gleason grade ≥ 8 was the only independent factor with MFS and OS. Conclusions: Without second-generation antiandrogens, nmCRPC patients with PSADT <10 months and in the initial very-high-risk group developed subsequent mCRPC in a significantly faster fashion. Patients of the very-high-risk group had shorter survival rates after nmCRPC.

Prior Local Therapy and First-Line Apalutamide in Patients With Nonmetastatic Castration-Resistant Prostate Cancer

Preclinical studies suggest that exposure to prostate-directed local therapy (LT) may influence the efficacy of subsequent systemic therapy including androgen receptor pathway inhibitors. However, there is insufficient clinical evidence to support this premise in patients with nonmetastatic castrate-resistant prostate cancer (nmCRPC). To determine whether exposure to prior prostate-directed LT (radical prostatectomy [RP], radiation therapy [RT], or both) played any effect-modifying role in the treatment effect of apalutamide on metastasis-free survival (MFS) and overall survival (OS) in patients with nmCRPC. This post hoc secondary analysis used individual patient data from SPARTAN (Study of Apalutamide [ARN-509] in Men With Non-Metastatic Castration-Resistant Prostate Cancer), a phase 3, double-blinded, placebo-controlled randomized clinical trial conducted at 332 sites in 26 countries. Between October 14, 2013, and December 15, 2016, patients with nmCRPC and a prostate-specific antigen doubling time of 10 months or less were randomly assigned to apalutamide vs placebo; all patients received androgen deprivation therapy. The final data analysis was performed on December 31, 2023. Prior prostate-directed LT. Separate Cox proportional hazards regression models were constructed for OS and MFS, which included prior LT, treatment group, and an interaction term, in addition to a minimally sufficient set of confounders. Adjusted hazard ratios (HRs) with 95% CIs for MFS and OS were determined for the apalutamide groups with or without prior LT. Among the 1179 evaluable patients included in this analysis, 795 received prior LT and 384 did not. The median age of patients with and without prior LT was 70 (IQR, 45-90) years and 75 (IQR, 50-95) years, respectively. The median follow-up was 52.0 (IQR, 51.5-52.8) months. A differential treatment effect of apalutamide on MFS was observed between patients with and without prior LT (P for interaction = .009), with greater benefits for those with prior LT (adjusted HR, 0.22 [95% CI, 0.17-0.27]) compared with those without prior LT (adjusted HR, 0.35 [95% CI, 0.25-0.51]). However, there was insufficient evidence of a differential treatment effect on OS among subgroups stratified by exposure to prior LT (P for interaction = .23), with improved OS in the subgroup with prior LT (adjusted HR, 0.72 [95% CI, 0.57-0.92]) but no significant difference in OS in the subgroup without prior LT (adjusted HR, 0.92 [95% CI, 0.64-1.31]). This post hoc analysis of the SPARTAN trial provides evidence of an interaction between prior LT and apalutamide in patients with nmCRPC, with a clinically significant and more favorable treatment effect from apalutamide on MFS among patients with prior LT. Further studies are needed to validate these findings. ClinicalTrials.gov Identifier: NCT01946204.

Immunotherapy Vaccines for Prostate Cancer Treatment.

Therapeutic tumor vaccines have emerged as a compelling avenue for treating patients afflicted with advanced prostate cancer (PCa), particularly those experiencing biochemical relapse or ineligible for surgical intervention. This study serves to consolidate recent research findings on therapeutic vaccines targeting prostate tumors while delineating prevalent challenges within vaccine research and development. We searched electronic databases, including PubMed, Web of Science, Embase, and Scopus, up to August 31, 2024, using keywords such as 'vaccine', 'prostate cancer', 'immunotherapy', and others. We reviewed studies on various therapeutic vaccines, including dendritic cell-based, antigen, nucleic acid, and tumor cell vaccines. Studies consistently showed that therapeutic vaccines, notably DC vaccines, had favorable safety profiles with few adverse effects. These vaccines, with varied antigenic formulations, demonstrated strong clinical outcomes, as indicated by metrics such as PSA response rates (9.5%-58%), extended PSA doubling times (52.9%-89.7%), overall survival durations (17.7-33.8 months), two-year mortality rates (0%-12.5%), biochemical relapse rates (42%-73%), and antigen-specific immune responses (33.3%-71.4% in responsive groups). While clinical data for tumor vaccines have illuminated robust evidence of tumoricidal activity, the processes of their formulation and deployment are riddled with complexities. Combining vaccines with other therapies may enhance outcomes, and future research should focus on early interventions and deciphering the immune system's role in oncogenesis.

Real-world outcomes following biochemical recurrence after definitive therapy with a short prostate-specific antigen doubling time: potential role of early secondary treatment.

The natural history of biochemical recurrence (BCR) managed with delayed hormonal therapy is well documented by data from Johns Hopkins. However, as many patients receive treatment prior to metastasis, we evaluated the natural history and role of prostate-specific antigen doubling time (PSADT) in a more contemporary cohort of BCR patients with nonmetastatic castration-sensitive prostate cancer (nmCSPC). Patients in the Veterans Health Administration (VHA; 01/01/06 to 06/22/20) with nmCSPC and BCR were divided into rapid ( ≤9 months) and less rapid ( >9 to ≤15 months) PSADT cohorts. Patients with PSADT >15 months were excluded as outcomes, even with delayed treatment, are excellent. Outcomes included time to first antineoplastic therapy after BCR, metastasis, metastasis-free survival (MFS), and overall survival (OS). Cox models adjusted for baseline demographics and clinical characteristics. Overall, 781 patients with BCR were identified (502 rapid; 279 less rapid PSADT). Rapid PSADT was associated with shorter time to first systemic antineoplastic therapy (median 11.4 vs. 28.3 months, adjusted hazard ratio [95% confidence interval] 2.17 [1.83-2.57]), metastasis (102.4 months vs. not reached, 1.79 [1.33-2.40]), MFS (76.1 vs. 106.3 months, 1.73 [1.33-2.24]), and OS (120.5 vs. 140.5 months, 1.76 [1.22-2.54]) versus less rapid PSADT. Most patients with rapid PSADT underwent secondary treatment within 1 year after BCR. More contemporary patients treated with early secondary treatment had better outcomes than historical data from patients who had delayed treatment. Whether these results reflect the benefits of early secondary treatment or overall improvements in prostate cancer outcomes over time requires further study.

First-Strike Rapid Predictive Dosimetry and Dose Response for 177Lu-PSMA Therapy in Metastatic Castration-Resistant Prostate Cancer.

We devised and clinically validated a schema of rapid personalized predictive dosimetry for 177Lu-PSMA-I&T in metastatic castration-resistant prostate cancer. It supersedes traditional empiric prescription by providing clinically meaningful predicted absorbed doses for first-strike optimization. Methods: Prostate-specific membrane antigen PET was conceptualized as a simulation study that captures the complex dosimetric interplay between tumor, marrow, and kidneys at a single time point. Radiation principles of fractionation, heterogeneity, normal-organ constraints (marrow, kidney), absorbed dose, and dose rate were introduced. We created a predictive calculator in the form of a free, open-source, and user-friendly spreadsheet that can be completed within minutes. Our schema achieves speed and accuracy by sampling tissue radioconcentrations (kBq/cm3) to be analyzed in conjunction with clinical input from the user that reflect dosimetric preconditions. The marrow-absorbed dose constraint was 0.217 Gy (dose rate, ≤0.0147 Gy/h) per fraction with an interfraction interval of at least 6 wk. Results: Our first 10 patients were analyzed. The first-strike mean tumor-absorbed dose threshold for any prostate-specific antigen (PSA) response was more than 10 Gy (dose rate, >0.1 Gy/h). The metastasis with the lowest first-strike tumor-absorbed dose correlated the best with the percentage decrease of PSA; its threshold to achieve hypothetical zero PSA was 20 Gy or more. Each patient's PSA doubling time can be used to personalize their unique absorbed dose-response threshold. The predicted mean first-strike prescription constrained by marrow-absorbed dose rate per fraction was 11.0 ± 4.0 GBq. Highly favorable conditions (tumor sink effect) were dosimetrically expressed as the combination of tumor-to-normal-organ ratios of more than 150 for marrow and more than 4 for kidney. Our schema obviates the traditional role of the SUV as a predictive parameter. Conclusion: Our rapid schema is feasible to implement in any busy real-world theranostics unit and exceeds today's best practice standards. Our dosimetric thresholds and predictive parameters can radiobiologically rationalize each patient's first-strike prescription down to a single becquerel. Favorable tumor-to-normal-organ ratios can be prospectively exploited by predictive dosimetry to optimize the first-strike prescription. The scientific framework of our schema may be applied to other systemic radionuclide therapies.

Predictive Value of the Prostate-specific Antigen Doubling Time for the Effectiveness of Metastasis-directed Radiotherapy in Patients With Oligometastases After Radical Treatment for Non-metastatic Prostate Cancer.

Data on metastasis-directed radiotherapy (MDRT) are limited, particularly regarding its association with the prostate-specific antigen (PSA) doubling time (PSADT). The present study evaluated the oncological outcomes of MDRT on the basis of the PSADT in oligo-recurrent prostate cancer patients. We retrospectively reviewed clinical data of 35 MDRTs for 29 patients at the Kitasato University Hospital, targeting oligometastatic prostate cancer developed after radical treatment for non-metastatic prostate cancer. Thirty-five MDRTs were classified into the PSADT >3 months (n=25) or PSADT ≤3 months group (n=10). Statistical analyses were performed to compare associations between the two PSADT groups and oncological outcomes such as progression-free survival (PFS) and PSA response after MDRT. There were no significant differences between the two groups in terms of the clinicopathological features. Kaplan-Meier analysis showed that PFS was significantly better in the PSADT >3 months group than in the PSADT ≤3 months group [median: 13.3 versus (vs.) 2.6 months, p=0.046]. Regarding castration sensitivity, the predictive role of PSADT >3 months was maintained in 21 patients who received MDRT without prior salvage hormone therapy (median PFS: 12.7 vs. 2.6 months, p=0.024). In the castration-resistant setting (n=14), the frequency of a decrease in serum PSA levels after MDRT by 90% was 54.5% (median PFS: 23.1 months). MDRT can provide benefit especially for patients with PSADT ≥3 months who had oligo-recurrence after the radical treatment for non-metastatic prostate cancer.

Predictors of Progression to Castration-resistant Prostate Cancer After Radical Prostatectomy in High-risk Prostate Cancer Patients.

To examine the specific time frame and identify associated risk factors from commencement of hormonal therapy to the onset of castration-resistant prostate cancer among patients who have developed biochemical recurrence following radical prostatectomy. We retrospectively reviewed the records of 92 patients who developed biochemical recurrence and received hormonal therapy as initial salvage treatment after radical prostatectomy for high-risk localized prostate cancer from 2005 to 2021. The castration-resistant prostate cancer-free survival rates from the commencement of salvage hormonal therapy were analyzed using log-rank methods. Cox proportional hazard regression was performed to analyze the risk factors associated with acquiring castration resistance. The patients were stratified based on those risk factors. During a median follow-up duration of 57 months, 24 (26.1%) patients developed castration-resistant prostate cancer. The 5- and 10-year castration-resistant prostate cancer-free survival rates were 73.6% and 54.5%, respectively. A multivariate analysis showed that Grade Group of 5 and prostate-specific antigen doubling time at biochemical recurrence of ≤3 months were independent predictors of castration-resistant prostate cancer. The 5-year castration-resistant prostate cancer-free survival rates in the low- and high-risk groups, stratified according to the aforementioned factors, were 85.4% and 47.6%, respectively. Patients in high Grade Group and short prostate-specific antigen doubling time after radical prostatectomy are more likely to develop resistance to salvage hormonal therapy.

PE052 Long-term management of BCR Following RARP: Using PSA doubling time kinetics to avoid overtreatment

PE052 Long-term management of BCR Following RARP: Using PSA doubling time kinetics to avoid overtreatment

Olaparib Without Androgen Deprivation for High-Risk Biochemically Recurrent Prostate Cancer Following Prostatectomy

Olaparib is a poly(adenosine diphosphate-ribose) polymerase inhibitor that provides benefit in combination with hormonal therapies in patients with metastatic prostate cancer who harbor homologous recombination repair (HRR) alterations. Its efficacy in the absence of androgen deprivation therapy has not been tested. To determine the activity of olaparib monotherapy among patients with high-risk biochemically recurrent (BCR) prostate cancer after radical prostatectomy. This phase 2, single-arm nonrandomized controlled trial enrolled genetically unselected patients across 4 sites in the US from May 2017 to November 2022. Eligible patients had BCR disease following radical prostatectomy, a prostate-specific antigen (PSA) doubling time of 6 months or shorter, an absolute PSA value of 1.0 ng/mL or higher, and a testosterone level of 150 ng/dL or higher. Treatment was with olaparib, 300 mg, by mouth twice daily until doubling of the baseline PSA, clinical or radiographic progression, or unacceptable toxic effects. The primary end point was a confirmed 50% or higher decline in PSA from baseline (PSA50). Key secondary end points were outcomes by HRR alteration status, as well as safety and tolerability. Of the 51 male patients enrolled (mean [SD] age, 63.8 [6.8] years), 13 participants (26%) had a PSA50 response, all within the HRR-positive group (13 of 27 participants [48%]). All 11 participants with BRCA2 alterations experienced a PSA50 response. Common adverse events were fatigue in 32 participants (63%), nausea in 28 (55%), and leukopenia in 22 (43%), and were consistent with known adverse effects of olaparib. In this nonrandomized controlled trial, olaparib monotherapy led to high and durable PSA50 response rates in patients with BRCA2 alterations. Olaparib warrants further study as a treatment strategy for some patients with BCR prostate cancer but does not have sufficient activity in those without HRR alterations and should not be considered for those patients. ClinicalTrials.gov Identifier: NCT03047135.

Clinical Factors That Influence Repeat 68Ga-PSMA-11 PET/CT Scan Positivity in Patients with Recurrent Prostate Cancer Under Observation After a Negative 68Ga-PSMA-11 PET/CT Scan: A Single-Center Retrospective Study.

This analysis aimed to identify clinical factors associated with positivity on repeat 68Ga-PSMA-11 PET/CT after a negative scan in patients with recurrent prostate cancer (PCa) under observation. Methods: This single-center, retrospective analysis included patients who underwent at least 2 68Ga-PSMA-11 PET/CT scans (PET1 and PET2) at UCLA between October 2016 and June 2021 for recurrent PCa with negative PET1 and no PCa-related treatments between the 2 scans. Using Prostate Cancer Molecular Imaging Standardized Evaluation criteria to define negative and positive scans, the final cohort was divided into PET2-negative (PET2-Neg) and PET2-positive (PET2-Pos). The same PET1 was used twice in the more than 2 PET cases with inclusion criteria fulfilled. Patient characteristics and clinical parameters were compared between the 2 cohorts using Mann-Whitney U test and Fisher exact test. Areas under the curve (AUCs) of the receiver operating characteristic and the Youden index were computed to determine the discrimination ability of statistically significant factors and specific cut points that maximized sensitivity and specificity, respectively. Results: The final analysis included 83 sets of 2 PET/CT scans from 70 patients. Thirty-nine of 83 (47%) sets were PET2-Neg, and 44 of 83 (53%) sets were PET2-Pos. Prostate-specific antigen (PSA) increased from PET1 to PET2 for all 83 (100%) sets of scans. Median PSA at PET1 was 0.4 ng/mL (interquartile range, 0.2-1.0) and at PET2 was 1.6 ng/mL (interquartile range, 0.9-3.8). We found higher serum PSA at PET2 (median, 1.8 vs. 1.1 ng/mL; P = 0.015), absolute PSA difference (median, 1.4 vs. 0.7 ng/mL; P = 0.006), percentage of PSA change (median, +270.4% vs. +150.0%: P = 0.031), and median PSA velocity (0.044 vs. 0.017 ng/mL/wk, P = 0.002) and shorter PSA doubling time (DT; median, 5.1 vs. 8.3 mo; P = 0.006) in the PET2-Pos cohort than in the PET2-Neg cohort. Receiver operating characteristic curves showed cutoffs for PSA at PET2 of 4.80 ng/mL (sensitivity, 34%; specificity, 92%; AUC, 0.66), absolute PSA difference of 0.95 ng/mL (sensitivity, 62%; specificity, 71%; AUC, 0.68), percentage of PSA change of a positive 289.50% (sensitivity, 48%; specificity, 82%; AUC, 0.64), PSA velocity of 0.033 ng/mL/wk (sensitivity, 57%; specificity, 80%; AUC, 0.70), and PSA DT of 7.91 mo (sensitivity, 71%; specificity, 62%; AUC, 0.67). Conclusion: Patients with recurrent PCa under observation after a negative 68Ga-PSMA-11 PET/CT scan with markedly elevated serum PSA levels and shorter PSA DT are more likely to have positive findings on repeat 68Ga-PSMA-11 PET/CT.

68Ga]Ga-PSMA-11 PET and Prostate Cancer Bone Metastases: Diagnostic Performance of Available Standardized Criteria.

In up to two thirds of prostate-specific membrane antigen (PSMA) PET scans, unspecific bone uptake has been described. The aim of this study was to estimate the diagnostic accuracy of [68Ga]Ga-PSMA-11 PET/CT for bone metastases and the occurrence of equivocal lesions. Methods: We analyzed retrospectively 118 patients who underwent a [68Ga]Ga-PSMA-11 PET/CT for initial staging or recurrence evaluation. Lesions were interpreted according to the PSMA reporting and data system (PSMA-RADS) and the prostate cancer molecular imaging standardized evaluation (PROMISE) criteria. The SUVmax and the localization of each lesion were recorded. A combination of prior or follow-up examinations was used as a reference standard to categorize benign and malignant lesions. Correlation between the final diagnosis and imaging or clinicobiochemical parameters was tested. The diagnostic accuracy was calculated for different cutoffs of PSMA-RADS criteria, for PROMISE criteria, and the sequential combination of both. Results: In total, 265 bone abnormalities were identified in 70 of 118 patients. Among these, 148 (55.8%) lesions in 50 (42.4%) patients were classified as PSMA-RADS-3B. There were no PSMA-RADS-3D lesions in our cohort. Equivocal lesions were more frequent on the ribs (30.6%) followed by the pelvis (26.5%), but in the ribs, such an uptake was malignant in 33.3% of cases versus 66.7% in the pelvis. A significant association was found between the final diagnosis and the SUVmax, prostate-specific antigen (PSA), PSA doubling time, International Society of Urological Pathology score, and the number of foci. The sensitivity and specificity were 100% and 63.6% for the PSMA-RADS-3B cutoff, respectively; 40.5% and 100% for the PSMA-RADS-4 cutoff, respectively; and 89.3% and 96.6% for both the PROMISE criteria and the sequential PSMA-RADS/PROMISE strategy, respectively. In the sequential method, the number of equivocal lesions was reduced from 147 to 2. We found that 53% of PSMA-RADS-3B lesions were malignant; 95.5% of lesions classified positive by the sequential method were true positives, whereas 32.6% were false negatives. Conclusion: [68Ga]Ga-PSMA-11 PET/CT has high accuracy for the diagnosis of bone metastases. Equivocal lesions constitute nearly half of the lesions seen on PSMA PET. The sequential combination of PSMA-RADS and PROMISE criteria reduces the number of lesions classified as equivocal. PSMA-RADS-3B lesions which are positive according to the PROMISE criteria should be considered highly suggestive of malignancy.

Abiraterone or Enzalutamide for Patients With Metastatic Castration-Resistant Prostate Cancer

Abiraterone acetate and enzalutamide are recommended as preferred treatments for metastatic castration-resistant prostate cancer (mCRPC), but differences in their relative efficacy are unclear due to a lack of head-to-head clinical trials. Clear guidance is needed for making informed mCRPC therapeutic choices. To compare clinical outcomes in patients with mCRPC treated with abiraterone acetate or enzalutamide. This retrospective, multicenter cohort study included patients with mCRPC in the US Department of Veterans Affairs health care system who initiated treatment with abiraterone acetate or enzalutamide between January 1, 2014, and October 30, 2022. Abiraterone acetate or enzalutamide. The study used inverse probability of treatment weighting to balance baseline characteristics between patients initiating abiraterone acetate or enzalutamide and evaluated restricted mean survival time (RMST) differences in overall survival (OS), prostate cancer-specific survival (PCS), time to next treatment switching or death (TTS), and time to prostate-specific antigen (PSA) response (TTR) at different time points after treatment initiation. The study included 5779 patients (median age, 74.42 years [IQR, 68.94-82.14 years]). Median follow-up was between 38 and 60 months. Patients initiating enzalutamide on average had longer OS than those initiating abiraterone acetate, with RMSTs of 24.29 months (95% CI, 23.58-24.99 months) and 23.38 months (95% CI, 22.85-23.92 months), respectively, and a difference in RMST of 0.90 months (95% CI, 0.02-1.79 months) at 4 years. Similarly, TTS and TTR were improved in patients initiating enzalutamide, with an RMST at 4 years of 1.95 months (95% CI, 0.92-2.99 months) longer for TTS and 3.57 months (95% CI, 1.76-5.38 months) shorter for TTR. For PCS, the RMST at 2 years was 0.48 months (95% CI, 0.01-0.95 months) longer. An examination of subgroups identified that enzalutamide initiation was associated with longer RMST in OS among patients without prior docetaxel treatment (1.14 months; 95% CI, 0.19-2.10 months) and in those with PSA doubling time of 3 months or longer (2.23 months; 95% CI, 0.81-3.66 months) but not among patients with prior docetaxel (-0.25 months; 95% CI, -2.59 to 2.09 months) or with PSA doubling time of less than 3 months (0.05 months; 95% CI, -1.05 to 1.15 months). In this cohort study of patients with mCRPC, initiation of enzalutamide was associated with small but statistically significant improvements in OS, PCS, TTS, and TTR compared with initiation of abiraterone acetate. The improvements were more prominent in short-term outcomes, including TTS and TTR, and in patient subgroups without prior docetaxel or with PSA doubling time longer than 3 months.

Long-term outcomes of the first prospective study of active surveillance for prostate cancer in Japan.

Active surveillance for prostate cancer was initiated in the early 2000s. We assessed the long-term outcomes of active surveillance in Japan. This multicenter prospective observational cohort study enrolled men aged 50-80years with stage cT1cN0M0 prostate cancer in 2002 and 2003. The eligibility criteria included serum prostate-specific antigen level ≤ 20ng/mL, ≤ 2 positive cores per 6-12 biopsy samples, Gleason score ≤ 6, and cancer involvement < 50% in the positive core. Patients were encouraged to undergo active surveillance. Prostate-specific antigen levels were measured bimonthly for 6months and every 3months thereafter. Triggers for recommending treatment were prostate-specific antigen doubling time of < 2years and pathological progression on repeat biopsy. Among 134 patients, 118 underwent active surveillance. The median age, prostate-specific antigen level at diagnosis, and maximum cancer occupancy were 70years, 6.5ng/mL, and 11.2%, respectively. Ninety-one patients had only one positive cancer core. The median observation period was 10.7years. At 1year, 65.7% underwent a repeat biopsy, and 37% of patients experienced pathological progression. The active surveillance continuation rates at 5, 10, and 15years were 28%, 9%, and 4%, respectively. One prostate cancer-related death occurred in a patient who refused treatment despite pathological progression at the one-year repeat biopsy. Active surveillance according to this study protocol was associated with conversion to the next treatment without delay, when indicated, despite the selection criteria and follow-up protocols being less rigorous than those recommended in current international guidelines.

PSA doubling time 4.65 months as an optimal cut-off of Japanese nonmetastatic castration-resistant prostate cancer

A multicenter study of nonmetastatic castration-resistant prostate cancer (nmCRPC) was conducted to identify the optimal cut-off value of prostate-specific antigen (PSA) doubling time (PSADT) that correlated with the prognosis in Japanese nmCRPC. Of the 515 patients diagnosed and treated for nmCRPC at 25 participating Japanese Urological Oncology Group centers, 450 patients with complete clinical information were included. The prognostic values of clinical factors were evaluated with respect to prostate specific antigen progression-free (PFS), cancer-specific survival (CSS), and overall survival (OS). The optimal cutoff value of PSADT was identified using survival tree analysis by Python. The Median PSA and PSADT at diagnosis of nmCRPC were 3.3 ng/ml, and 5.2 months, respectively. Patients treated with novel hormonal therapy (NHT) showed significantly longer PFS (HR: hazard ratio 0.38, p < 0.0001) and PFS2 (HR 0.45, p < 0.0001) than those treated with vintage nonsteroidal antiandrogen agent (Vintage). The survival tree identified 4.65 months as the most prognostic PSADT cutoff point. Among the clinical and pathological factors PSADT of < 4.65 months remained an independent prognostic factor for OS (HR 2.96, p = 0.0003) and CSS (HR 3.66, p < 0.0001). Current data represented optimal cut-off of PSADT 4.65 months for a Japanese nmCRPC.

Clinical factors predicting the outcome of salvage radiotherapy for patients with biochemical recurrence after radical prostatectomy.

It remains unclear which patients with biochemical recurrence after prostatectomy are most suitable for salvage radiotherapy. We evaluated the parameters related to outcomes. We retrospectively evaluated patients who underwent salvage therapy for biochemical recurrence after prostatectomy between 2005 and 2019. This study aimed to evaluate biochemical recurrence-free survival (bRFS) after salvage radiotherapy and elucidate the parameters associated with bRFS. The bRFS rate was calculated using the Kaplan-Meier method, and the parameters associated with bRFS were evaluated using Cox regression analysis. This study included 67 patients treated with salvage radiotherapy with a median age of 67years at salvage radiotherapy. The median follow-up period after salvage radiotherapy was 7.3years. The 5-year bRFS rate following salvage radiotherapy was 47.1%. Univariate analysis showed that PSA doubling time < 6months, positive surgical margin, and pathological Gleason score ≥ 8 were significantly associated with shorter bRFS (p < 0.001, p = 0.036, p = 0.047, respectively). Multivariable analysis showed that a PSA doubling time < 6months and positive surgical margins were significantly associated with shorter bRFS (p = 0.001 and p = 0.018, respectively). No serious adverse events were observed. In our hospital, approximately half of the patients are under long-term control with salvage radiotherapy. A PSA doubling time of < 6months and positive surgical margins were suggested to be associated with poor outcomes of salvage radiotherapy.

Towards improved diagnosis: radiomics and quantitative biomarkers in 18 F-PSMA-1007 and 18 F-fluorocholine PET/CT for prostate cancer recurrence.

This study compared the radiomic features and quantitative biomarkers of 18 F-PSMA-1007 [prostate-specific membrane antigen (PSMA)] and 18 F-fluorocholine (FCH) PET/computed tomography (CT) in prostate cancer patients with biochemical recurrence (BCR) enrolled in the phase 3, prospective, multicenter BIO-CT-001 trial. A total of 106 patients with BCR, who had undergone primary definitive treatment for prostate cancer, were recruited to this prospective study. All patients underwent one PSMA and one FCH PET/CT examination in randomized order within 10 days. They were followed up for a minimum of 6 months. Pathology, prostate-specific antigen (PSA), PSA doubling time, PSA velocity, and previous or ongoing treatment were analyzed. Using LifeX software, standardized uptake value (SUV) maximum, SUV mean , PSMA and choline total volume (PSMA-TV/FCH-TV), and total lesion PSMA and choline (TL-PSMA/TL-FCH) of all identified metastatic lesions in both tracers were calculated. Of the 286 lesions identified, the majority 140 (49%) were lymph node metastases, 118 (41.2%) were bone metastases and 28 lesions (9.8%) were locoregional recurrences of prostate cancer. The median SUV max value was significantly higher for 18 F-PSMA compared with FCH for all 286 lesions (8.26 vs. 4.99, respectively, P < 0.001). There were statistically significant differences in median SUV mean , TL-PSMA/FCH, and PSMA/FCH-TV between the two radiotracers (4.29 vs. 2.92, 1.97 vs. 1.53, and 7.31 vs. 4.37, respectively, P < 0.001). The correlation between SUV mean /SUV max and PSA level was moderate, both for 18 F-PSMA ( r = 0.44, P < 0.001; r = 0.44, P < 0.001) and FCH ( r = 0.35, P < 0.001; r = 0.41, P < 0.001). TL-PSMA/FCH demonstrated statistically significant positive correlations with both PSA level and PSA velocity for both 18 F-PSMA ( r = 0.56, P < 0.001; r = 0.57, P < 0.001) and FCH ( r = 0.49, P < 0.001; r = 0.51, P < 0.001). While patients who received hormone therapy showed higher median SUV max values for both radiotracers compared with those who did not, the difference was statistically significant only for 18 F-PSMA ( P < 0.05). Our analysis using both radiomic features and quantitative biomarkers demonstrated the improved performance of 18 F-PSMA-1007 compared with FCH in identifying metastatic lesions in prostate cancer patients with BCR.