High-risk Prostate Cancer Research Articles

The association between the interval from biopsy to radical prostatectomy and biochemical recurrence in patients with intermediate- and high-risk prostate cancer

ObjectiveTo investigate the association between the interval from biopsy to radical prostatectomy (RP) and biochemical recurrence (BCR) in prostate cancer patients.MethodsWithin a tertiary-care database (01/2014 to 06/2023), D’Amico intermediate- and high-risk prostate cancer patients were stratified according to interval from biopsy to RP (≤3 vs. >3-≤6 months). Kaplan-Meier survival analyses and Cox regression models addressed BCR.ResultsOf 680 patients, 328 vs. 153 exhibited intermediate-risk prostate cancer and had interval from biopsy to RP ≤3 vs. >3-≤6 months. Similarly, 158 vs. 41 exhibited high-risk prostate cancer and had interval from biopsy to RP ≤3 vs. >3-≤6 months. Median interval from biopsy to RP was 59 vs. 113 days in intermediate- and 55 vs. 117 days in high-risk patients, respectively. In both intermediate- and high-risk patients, rates of adverse histopathological outcomes, namely pT3/pT4, pN1, and R1 status, did not differ according to interval from biopsy to RP. In survival analyses, three-year BCR-free survival rates were 82 vs. 88% in intermediate-risk (p=0.5) and 76 vs. 75% in high-risk patients (p=1). In multivariable Cox regression models, BCR did not significantly differ according to interval from biopsy to RP in intermediate- (hazard ratio 0.85, 95% confidence interval 0.49-1.46; p=0.5) and high-risk patients (hazard ratio 1.05, 95% confidence interval 0.50-2.22; p=0.9).ConclusionsBoth intermediate- and high-risk prostate cancer patients with an interval from biopsy to RP >3-≤6 months did not differ from those treated with RP ≤3 months after biopsy, regarding adverse histopathological outcomes and BCR rates. Therefore, it might be safe to postpone RP up to six months.

Optimizing Oncological and Functional Outcomes with Wide Resection Techniques in Robot-Assisted Radical Prostatectomy for Very High-Risk Prostate Cancer: A Single-Institution Retrospective Study

Optimizing Oncological and Functional Outcomes with Wide Resection Techniques in Robot-Assisted Radical Prostatectomy for Very High-Risk Prostate Cancer: A Single-Institution Retrospective Study

Novel Intraprostatic Magnetic Resonance-Guided Implantation of Multidrug-Eluting Microdevice for Testing of Systemic Therapy Agents In Situ: Proof of Concept in Intermediate-Risk and High-Risk Prostate Cancer: Erratum.

Novel Intraprostatic Magnetic Resonance-Guided Implantation of Multidrug-Eluting Microdevice for Testing of Systemic Therapy Agents In Situ: Proof of Concept in Intermediate-Risk and High-Risk Prostate Cancer: Erratum.

Immunohistochemical Analysis of Androgen Receptor Expression Predicts the Prognosis of Metastatic Castration-Sensitive Prostate Cancer Patients Receiving Abiraterone Acetate.

The efficacy of abiraterone acetate varies among patients with high-risk metastatic castration-sensitive prostate cancer (mCSPC). Both androgen receptor (AR) and cytokeratin 18 (CK18) are markers of the luminal lineage of prostate cancer, and their expression levels have been suggested to affect the response to androgen deprivation therapy (ADT). This study aimed to predict the efficacy of abiraterone acetate in high-risk mCSPC via immunohistochemical staining of biopsy specimens obtained at the time of prostate cancer diagnosis. We retrospectively analyzed 44 patients treated with abiraterone acetate in combination with ADT. AR and CK18 expression in prostate biopsy specimens were assessed using immunohistochemical staining. AR and CK18 staining was not significantly associated with overall survival (OS). However, low AR staining was significantly associated with a shorter time to castration-resistant prostate cancer (TTCRPC) compared with high AR staining (log-rank test, p = 0.018). Similarly, low CK18 staining was significantly associated with a shorter TTCRPC compared with high CK18 staining (log-rank test, p = 0.037). Immunohistochemical analysis of AR or CK18 expression in biopsy specimens may serve as a predictive biomarker of high-risk mCSPC treated with abiraterone acetate. None.

A novel prostate cancer-specific fluorescent probe based on extracellular vesicles targeting STEAP1 applied in fluorescence guided surgery.

Radical prostatectomy with pelvic lymph node dissection is the best treatment for intermediate- to high-risk localized prostate cancer (PCa). However, conventional white light surgery has difficulties in identifying tumor boundary and micrometastases intraoperatively. Fluorescence guided surgery (FGS) can solve the above difficulties, but lacks tumor-specific near-infrared fluorescent (NIRF) probes in PCa. STEAP1 was an ideal target in PCa treatment and imaging. Here, we constructed a PCa specific fluorescent probe based on extracellular vesicles targeting STEAP1 (AS-EVs) loaded with NIRF dye S0456 and evaluated its preclinical profiles. In vitro and in vivo studies both showed S0456@AS-EVs was safe and showed strong targeting ability to PCa in various mice xenograft models. S0456@AS-EVs could clear rapidly from blood (half-time of 4.29 h) and retain in the STEAP1 positive tumor tissues for more than 72 h with the highest tumor background ratio (TBR) of 3:1, which was superior to ICG, free S0456, ICG@Ctrl-EVs and S0456@Ctrl-EVs (p < 0.01). Finally, S0456@AS-EVs was applied in FGS on intramuscular model, and the tumors were resected under white light and fluorescence respectively. Compared with white light surgery, mice undergoing FGS had lower positive margin rate and better postoperative survival (p = 0.0342).

Utilization of patient-reported outcomes to assess adherence to relugolix when combined with stereotactic body radiation therapy for intermediate to high-risk prostate cancer

Utilization of patient-reported outcomes to assess adherence to relugolix when combined with stereotactic body radiation therapy for intermediate to high-risk prostate cancer

External Validation of Nomograms for the Identification of Pelvic Nodal Dissection Candidates Among Prostate Cancer Patients with Negative Preoperative Prostate-specific Membrane Antigen Positron Emission Tomography.

Extended pelvic lymph node dissection (ePLND) is recommended in selected radical prostatectomy (RP) prostate cancer (PCa) patients for staging purposes. We aim to externally validate available tools to predict lymph node invasion (LNI) in men with negative preoperative prostate-specific membrane antigen positron emission tomography (miN0). Overall, 282 intermediate- to high-risk PCa patients with miN0 disease undergoing RP and ePLND at ten centers between 2016 and 2023 were identified. The Memorial Sloan Kettering Cancer Center (MSKCC); Amsterdam-Brisbane-Sydney; and Briganti 2017, 2019, and 2023 tools predicting LNI were validated externally using calibration plots, C-indexes, and decision-curve analyses to assess calibration, discrimination, and net benefit. Overall, 36 (13%) patients had LNI. The C-indexes of the MSKCC, Briganti 2017, Briganti 2019, Amsterdam-Brisbane-Sydney, and Briganti 2023 nomograms were 64%, 69%, 72%, 64%, and 77%, respectively. The Briganti 2023 nomogram exhibited higher net benefit than the other available nomograms, and the use of a 5% cutoff would have spared 47% ePLND procedures (vs 14% and 4.3% for the Briganti 2019 and Amsterdam-Brisbane-Sydney nomograms, respectively) at the cost of missing only five (3.8%) LNI cases. Heterogeneity in patient selection and imaging protocols represents the main limitations. The Briganti 2023 nomogram outperformed other available tools in predicting LNI in men with miN0 PCa. The use of this tool resulted in a considerable number of unnecessary ePLND procedures spared and optimization of ePLND recommendations in a contemporary clinical setting.

Association of [68Ga]Ga-PSMA-11 PET/CT Metrics with PSA Persistence Following Radical Prostatectomy in Patients with Intermediate- and High-Risk Prostate Cancer

Background/Objectives: The aim of this study was to determine whether semiquantitative and volume-based metrics obtained from [68Ga]Ga-PSMA-11 PET/CT (PSMA-PET) scans before radical prostatectomy (RP) are associated with PSA persistence after surgery in patients with intermediate- (IR) and high-risk (HR) prostate cancer (PCa). Methods: We included 118 consecutive patients (IR = 57; HR = 61) with PCa with a PSMA-PET for initial staging and underwent subsequent RP. Clinical parameters and PSMA-PET metrics in the prostate were obtained to determine the following measurements: SUVmax, SUVmean, Target-to-Background Ratios (TBRs), Prostate Molecular Tumor (pMTV), Prostate Total Lesion Activity (pTLA), Prostate Volume (pV), and Prostate Disease Burden (pDB). The association of PSMA-PET metrics parameters before RP and PSA persistence were analyzed by multivariate logistic regression. Results: SUVmax and volume-based PSMA-PET metrics were significantly higher in patients with ISUP Grade 3–5 vs. ISUP Grade 1–2, and only pMTV, pTLA, and pDB were found to be significantly higher in HR patients, as compared with the IR group. During follow-up, 23 patients showed PSA persistence. pMTV, pTLA, and pDB were significantly higher among patients presenting PSA persistence after RP than in patients with undetectable PSA. Multivariate logistic regression analysis found that lymph node infiltration and pTLA were independent predictors for PSA persistence. A cut-off point of ≥25.1 allowed the best discrimination for PSA persistence (OR: 7.4; IQR: 1.4–39.1; p &lt; 0.05). Conclusions: The identified association between PSA persistence and prostate TLA of PSMA-PET at initial staging highlights its potential as a valuable tool to improve risk prediction in prostate cancer patients. Further research is needed to confirm these results.

XCT as a potential marker for neuroendocrine cells in high-risk prostate cancer and the relation to AL122023.1-miR-26a/30d/30e axis.

Prostate cancer is the second most common type of cancer in male worldwide. Stromal-epithelial interaction is thought to have a major impact on cancer development and progression. Previous studies have shown that interaction via soluble factors lead to a reduction in the expression of xCT and AL122023.1 in the prostate carcinoma cell line LNCaP after seven days of co-culture with primary stromal p21 cells. In this study, we validated the repression of xCT and AL122023.1 at RNA level using quantitative real-time PCR and at protein level by Western Blotting. Furthermore, xCT is known to be a putative target for miRNAs miR-26a, miR-30d and miR-30e, which in turn potentially interact with AL122023.1. The lncRNA-miRNA-interaction was verified by luciferase reporter assays. However, miR-26a/-30d/-30e did not inhibit xCT expression at protein level. Nevertheless, indirect inhibitory effect of AL122023.1 on the xCT expression could be shown. Moreover, immunostaining revealed precise xCT expression in neuroendocrine cells, ranging from fetal, healthy juvenile, and adult prostate tissue to benign prostatic hyperplasia and finally advanced prostate cancer. This study explores the relevance and function of xCT and AL122023.1 in the prostate and exposes xCT as a potential marker or therapeutic target in high-risk prostate cancer.

External beam radiation therapy versus radical prostatectomy for high-risk prostate cancer: protocol of the RECOVER study

BackgroundThis paper describes the rationale and design of the RECOVER study. Currently, there is no consensus regarding the optimal treatment for high-risk, non-metastatic prostate cancer (PCa). The study primarily aims to evaluate and compare the impact of treatment with robot-assisted radical prostatectomy (RP) versus external beam radiation therapy (EBRT) with androgen deprivation therapy (ADT) for men with high-risk, non-metastatic PCa regarding health-related quality of life (HRQoL) and functional outcomes. Secondary objectives are progression-free survival (PFS), distant metastasis-free survival (DMFS), costs and cost-effectiveness.MethodsThe RECOVER study is a comparative effectiveness study that prospectively includes newly diagnosed high-risk (cT3a-bN0M0, ISUP-grade ≥ 4 and/or PSA > 20 ng/mL), non-metastatic PCa patients. Four Dutch prostate cancer networks, comprising 29 hospitals, are currently participating in the study. Patient reported outcomes are collected before treatment initiation, 12 months and 36 months after treatment initiation and include the EORTC-QLQ-C30, the EPIC-26, an adapted version of the SCQ, an adapted version of the iMTA Productivity Cost Questionnaire and several specific questions regarding patient characteristics, treatment of PCa specific complaints and health resources used. Clinical data regarding patient-, tumor- and treatment characteristics and oncological outcomes are collected up to 5 years after diagnosis. For sufficient power, patient reported outcomes of 471 patients must be collected 36 months after treatment initiation. Descriptive statistics and mixed-effects models are used to assess differences in HRQoL and functional outcomes over time between the patients treated with radical prostatectomy versus EBRT (+ ADT). Inverse probability of treatment weighting or the g-formula are used to adjust for confounding covariates associated with treatment. Secondary endpoints PFS and DMFS are evaluated using a competing risk analysis and cost-utility and budget-impact analyses will be performed to determine cost and cost-effectiveness.DiscussionAn observational prospective design was chosen since a randomized controlled trial comparing surgery and radiotherapy was not deemed feasible. This study evaluates effectiveness of treatment in a routine clinical setting (with adjustment for confounding) and its findings will enhance patients’ and healthcare professionals’ awareness for the impact of both treatment modalities on (long-term) daily functioning and HRQoL and aid treatment decision making.Trial registrationThis study is registered at ClinicalTrials.gov (NCT05931419).

P53-loss induced prostatic epithelial cell plasticity and invasion is driven by a crosstalk with the tumor microenvironment

Prostate cancer is a heterogeneous disease with a slow progression and a highly variable clinical outcome. The tumor suppressor genes PTEN and TP53 are frequently mutated in prostate cancer and are predictive of early metastatic dissemination and unfavorable patient outcomes. The progression of solid tumors to metastasis is often associated with increased cell plasticity, but the complex events underlying TP53-loss-induced disease aggressiveness remain incompletely understood. Using genetically engineered mice, we show that Trp53 deficiency in Pten-null prostatic epithelial cells (PECs) does not impact early cell proliferation and neoplasia formation, nor growth arrest and senescence entry at a later time. However, Trp53-deficiency enhances invasive adenocarcinoma development and promotes metastatic cell dissemination. Importantly, our single-cell transcriptomic and chromatin accessibility analyses combined with histological examinations uncovered an epithelial cell population characterized by an induction of Jak/Stat3 signaling and displaying mesenchymal features. Moreover, we show that the transcriptomic signature of this cell population is prominent in tumors of patients with high-risk prostate cancer or metastatic disease. In addition, our in vivo and organoid-based experiments provide evidence that PEC plasticity occurs through bi-directional communication with cancer-associated fibroblasts (CAFs). Thus, our study demonstrates that p53 loss induces a protumorigenic crosstalk between PECs and CAFs, and identifies new vulnerabilities that might be targeted to limit cancer progression.

Discordance between prostate MRI and PSMA-PET/CT: the next big challenge for primary prostate tumor assessment?

An increasing number of patients with prostate cancer (PCa) undergo assessment with magnetic resonance imaging (MRI) and prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT). This offers comprehensive multimodality staging but can lead to discrepancies. The objective was to assess the rates and types of discordance between MRI and PSMA-PET/CT for primary PCa assessment. Consecutive men diagnosed with intermediate and high-risk PCa who underwent MRI and PSMA-PET/CT in 2021-2023 were retrospectively included. MRI and PSMA-PET/CT were interpreted using PI-RADS v2.1 and PRIMARY scores. Discordances between the two imaging modalities were categorized as "minor" (larger or additional lesion seen on one modality) or "major" (positive on only one modality or different index lesions between MRI and PSMA-PET/CT) and reconciled using radical prostatectomy or biopsy specimens. Three hundred and nine men (median age 69 years, interquartile range (IQR) 64-75) were included. Most had Gleason Grade Group ≥ 3 PCa (70.9% (219/309)). Median PSA was 9.0 ng/mL (IQR 5.6-13.6). MRI and PSMA-PET/CT were concordant in 157/309 (50.8%) and discordant in 152/309 (49.1%) patients; with 39/152 (25.7%) major and 113/152 (74.3%) minor discordances. Of 27 patients with lesions only seen on MRI, 85.2% (23/27) were clinically significant PCa (csPCa). Of 23 patients with lesions only seen on PSMA-PET/CT, 78.3% (18/23) were csPCa. Altogether, lesions seen on only one modality were csPCa in 80.0% (36/45). MRI and PSMA-PET/CT were discordant in half of patients for primary PCa evaluation, with major discrepancies seen in roughly one out of eight patients. Question While both MRI and PSMA-PET/CT can be used for primary tumor assessment, the discordances between them are not well established. Findings MRI and PSMA-PET/CT were discordant in about half of the patients. Most prostate lesions seen on only one modality were significant cancer. Clinical relevance MRI and PSMA-PET/CT are often discordant for assessing the primary prostate tumor. Using both modalities for primary prostate tumor evaluation can provide complementary information that may substantially impact treatment planning.

HDR brachytherapy combined with external beam radiotherapy for unfavorable localized prostate cancer: A single center experience from inception to standard of care.

High dose rate (HDR) brachytherapy is increasingly adopted for dose escalation in prostate cancer treatment. We report the clinical efficacy and toxicity of HDR prostate brachytherapy combined with external beam radiotherapy (EBRT) and evaluate the predictability of the biochemical definition of cure of 4-year PSA ≤0.2 ng/mL for failure free survival (FFS). A single centre retrospective study was conducted, including all patients with high-tier intermediate risk and high-risk prostate cancer treated with HDR brachytherapy combined with EBRT from 2011 to 2019. Patient and prostate cancer characteristics, treatment, clinical endpoints, and follow up were collected. Total 319 patients were analyzed. The median age was 68 with median follow up of 77.1 months. Total 142 had high-tier intermediate and 177 had high-risk disease. Brachytherapy doses were initially 20 Gy/2 fractions, and subsequently 15 Gy/1 fraction. All patients received 46 Gy/23 fractions of EBRT. Overall survival at 5 and 9 years was 92.2% and 77.0%, respectively. Failure-free survival (FFS) was 86.0% at 5 years and 76.1% at 9 years. PSA ≤ 0.2 ng/mL at 4 years was seen in 79.3% of patients and was associated with FFS of 94.1% at 9 years. Grade 3 urethral stricture, hematuria, or proctitis occurred in 2.8%, 0%, and 0%, respectively. HDR brachytherapy in addition to EBRT is effective treatment for unfavourable localized prostate cancer with a very acceptable toxicity profile. The biochemical definition of cure of PSA < 0.2 ng/mL at 4 years was predictive for FFS at 9 years.

Prostate-specific antigen screening at low thresholds of men with pathogenic BRCA1/2 variants.

Men with pathogenic BRCA1/2 variants are at higher risk of prostate cancer We included men with likely pathogenic/pathogenic (LP/P) variants in BRCA1/2 in a prostate-specific antigen (PSA) screening program after cascade germline testing since 2014. PSA was tested yearly and an age-specific low PSA threshold for biopsy was used, to determine if a low PSA threshold for biopsy is justified for men with pathogenic BRCA1/2 variants. From 2014 to 2023 a total of 340 men were included in the program. We report demographics, clinical characteristics, and treatment outcomes at 7 years. The cumulative incidence of a primary biopsy was 37% (95CI: 31‒43) after 7 years. Incidence of prostate cancer diagnosis was 11% (95CI: 7.1‒15). Men referred were 7.8 (95CI: 5.3‒11, p < 0.001) times more likely to be diagnosed with prostate cancer than the general Danish male population. The cumulative incidence of biochemical failure (PSA > = 0.2 ng/ml) 4 years after RP was 22% (95CI: 2.3‒41). The main limitation is that not all men underwent a pre-biopsy MRI. We found a high incidence of prostate cancer in men with LP/P BRCA1/2 variants, but this may be explained by the low PSA threshold for scheduling biopsies. More studies are needed to compare this patient population to men with other germline features. The high risk of recurrence after curative therapy is worrisome and requires further evaluation as to whether this is a biological phenomenon.

Highly hypofractionated biaxially rotational dynamic radiation therapy (BROAD-RT) for high-risk prostate cancer.

To report clinical outcomes following highly hypofractionated biaxially rotational dynamic radiation therapy (BROAD-RT), a unique radiation therapy method that facilitates non-coplanar volumetric-modulated arc therapy (VMAT) without the need to rotate the couch or reposition the patient, for high-risk prostate cancer (PCa) with simultaneous integrated boost (SIB) for intra-prostatic dominant lesions (IPDLs), we performed a single-center prospective pilot study. In this study, patients with high-risk PCa according to the D'Amico classification or those with cT3aN0M0 PCa were eligible. VMAT was performed using BROAD-RT, and a dose of 54 Gy in 15 fractions was prescribed for the prostate in combination with SIB for IPDLs at a dose of 57 Gy in 15 fractions. Short-term neoadjuvant androgen-deprivation therapy (median: 6.9 months) was conducted. Neither adjuvant androgen-deprivation therapy nor fiducial marker implantation to the prostate was applied for any patient. In total, 26 patients were registered in this study between August 2018 and November 2020. Their median age was 73 years at the initiation of RT. The median follow-up period was 49.7 months. The 4-year cumulative incidence rates of grade 2 late GU and GI toxicities were 15.4 and 3.8%, respectively. No grade 3 or higher acute or late toxicities were observed. The 4-year biochemical failure-free survival rates were 87.7%. In conclusion, highly hypofractionated RT using BROAD-RT for high-risk PCa with SIB for IPDLs was feasible and facilitated favorable oncological outcomes. Therefore, this approach is considered a promising method to achieve safe dose escalation and shorten the treatment duration.

« Augmented radiotherapy » in the management of high-risk prostate cancer (PCa): A systematic review.

In patients with high-risk (HR) prostate cancer (PCa) treated with radiotherapy and androgen deprivation therapy (ADT), intensification with androgen receptor pathway inhibitor (ARPI) improves overall survival (OS), at the cost of significant side-effects. We hypothesized that "augmented RT" schedules (defined as either dose-escalation on the prostate gland over 78 Gy and/or addition of whole pelvic radiotherapy (WPRT)), combined with long-term ADT can reach excellent prostate cancer specific survival (PCSS) in this population with little detrimental impact on quality of life. We searched Pubmed database until February 8, 2024. Studies reporting both oncological and toxicity outcomes after "augmented RT" were deemed eligible. Studies without ADT or with ARPI intensification were deemed ineligible. Dose-escalation within the prostate gland at doses over 78 Gy halved the risk of biochemical recurrence at 5 years, with however no impact on PCSS. The addition of WPRT provides a 5-year disease-free survival (DFS) reaching 89.5 % at 5 years, with no significant increase in late grade≥ 2 genito-urinary (GU) or gastrointestinal (GI) toxicity. Combined approaches result in 9-year PCSS ranging between 96.1 % and 100 %. Most approaches demonstrated excellent safety profiles. "Augmented RT" reached excellent oncological outcomes, with minimal additional toxicity. The development of biomarkers might lead to further treatment personalization, in the rapidly evolving landscape of systemic therapies.

Screening for Predictive Factors of Efficacy of Second-Generation Androgen Receptor Axis-Targeted Agents in Patients With High-Risk Metastatic Hormone-Sensitive Prostate Cancer.

Differences in the effectiveness of second-generation androgen receptor axis-targeted agents (ARATs) in high-risk metastatic hormone-sensitive prostate cancer (mHSPC) remain unclear. This study aimed to identify the factors influencing the efficacy of ARATs in patients with high-risk mHSPC and compare their long-term effectiveness. Four hundred and sixty-six patients with mHSPC treated with ARATs were retrospectively recruited from our hospital and affiliated hospitals of the Kindai Oncology Study Group and Kyoto Prefectural University of Medicine Oncology Study Group between December 2013 and March 2024. Cox proportional hazards analysis was performed to identify prognostic factors for overall survival in patients with mHSPC. Propensity score matching was used to adjust for the differences in clinical backgrounds of the patients. Univariate and multivariable analyses revealed that Gleason pattern 5 and pretreatment ALP levels were notable prognostic factors for overall survival in patients with mHSPC treated with ARATs. In the subgroup of patients with high-risk mHSPC with Gleason pattern 5, apalutamide and enzalutamide showed significantly better outcomes in terms of PSA-PFS, PFS2, and overall survival compared to abiraterone acetate though selection bias and the small number of patients may be associated with the results in this study. Univariate and multivariable analyses suggested that ARATs selection (ABI vs. APA or ENZ) may serve as an independent predictor of overall survival in patients with high-risk mHSPC with Gleason pattern 5 treated with ARATs. Gleason pattern 5 may be a predictive factor for ARAT efficacy in patients with high-risk mHSPCs.

Development of Novel Nomograms to Predict 5- and 7-Year Biochemical-Recurrence-Free Survival in High-Risk Prostate Cancer Patients After Carbon-Ion Radiotherapy and Androgen Deprivation Therapy

Background: The aim of this study was to develop nomograms predicting 5- and 7-year biochemical-recurrence (BCR)-free survival in high-risk prostate cancer (PCa) patients treated with carbon-ion radiotherapy (CIRT) and androgen deprivation therapy (ADT). Methods: We retrospectively evaluated 785 high-risk PCa patients treated with CIRT and ADT. Based on the least absolute shrinkage and selection operator model, two nomograms predicting 5- and 7-year BCR-free survival were developed and internally validated. The ability of each nomogram to predict BCR-free survival was determined by calculating the area under the survival curve (AUC). Results: The 5- and 7-year BCR-free survival rates were 92.1% and 89.3%, respectively. Age, prostate-specific antigen level, clinical T stage, and Gleason score were incorporated into the nomogram predicting 5-year BCR-free survival. In addition to these variables, the percentage of positive biopsy cores was also added to the nomogram predicting 7-year BCR-free survival. The AUC value of each nomogram showed suboptimal-to-good discrimination. Conclusions: We developed the first nomograms accurately predicting BCR-free survival in high-risk PCa patients treated with CIRT and ADT. These nomograms will enable adequate understanding and explanation of BCR-free survival to patients when clinicians use them.

Evaluation of clinical risk stratification to determine benefit from long-term versus short-term androgen deprivation in high-risk localized prostate cancer.

Patients treated with RT and long-term androgen deprivation therapy (ltADT) for high-risk localized prostate cancer (HRLPC) with 1 high-risk factor (any of Gleason ≥8, PSA > 20 ng/mL, ≥cT3; "high-risk") have better outcomes than those with 2-3 factors and/or cN1 disease ("very high risk"). We evaluated whether this risk stratification could determine benefit from ltADT versus short-term (stADT). The Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) repository of randomized trials was queried to identify eligible patients and trials. The key outcomes of interest were metastasis-free survival (MFS), overall survival (OS), time to metastasis (TTM) and prostate cancer-specific mortality (PCSM). Stratified Cox and Gray's regression were used to obtain the overall treatment effect for outcomes and risk groups, and the Wald interaction test to estimate whether treatment benefit differed by risk group or trial. Heterogeneity of studies was assessed by Cochran's Q and I2. 2780 patients from 3 trials were included. Patients with very-high risk disease had greater benefit with ltADT compared to high-risk disease (MFS HR 0.77 [0.68-0.88] vs. 0.89 [0.76-1.03]; TTM 0.61 [0.51-0.74] vs. 0.77 [0.59-0.99]; PCSM 0.71 [0.56-0.90] vs. 0.82 [0.59-1.14]; OS 0.87 [0.76-1.00] vs. 0.93 [0.79-1.08]), but there was no statistically significant difference in treatment effect by risk group (p-interaction >0.1). Heterogeneity for treatment effect across trials was low in the very high-risk group and moderate in the high-risk group. Clinical risk stratification merits further evaluation in clinical trials to identify which patients with HRLPC may benefit from ltADT versus stADT.

Prospective Head-to-Head Comparison of 18F-PSMA PET/CT and 18F-NaF PET/CT for Assessing Bone Metastases in 160 Patients with Newly Diagnosed High-Risk Prostate Cancer.

Prostate-specific membrane antigen (PSMA) PET/CT is increasingly used for primary staging in prostate cancer (PC), mainly because of its improved accuracy in detecting lymph node metastases compared with conventional imaging. However, the diagnostic benefit of PSMA PET/CT for detecting bone metastases is less well established. This study compares the diagnostic accuracy of 18F-PSMA PET/CT and 18F-NaF PET/CT for detecting bone metastases in patients newly diagnosed with PC. Methods: This prospective study included patients with histologically confirmed high-risk PC. All participants were referred from the department of urology to 18F-NaF PET/CT and underwent 18F-PSMA PET/CT within 3 weeks. Images were reviewed by 2 nuclear medicine physicians unaware of the results of the other imaging modality. Presence or absence of bone metastases and number of metastatic lesions were recorded. A reference standard was established at the patient level based on agreement between the 2 imaging modalities. In cases of concordance, both modalities were deemed correct. In cases of discordance, additional follow-up scans were performed. Diagnostic performance metrics, including sensitivity, specificity, and accuracy, were calculated. Results: In total, 160 participants were included. Sensitivity, specificity, and accuracy for detecting bone metastases at the patient level were 0.98, 0.99, and 0.99, respectively, for 18F-PSMA PET/CT, and 0.91, 1.00, and 0.97, respectively, for 18F-NaF PET/CT. No significant differences were found. The concordance rate of bone metastases between 18F-NaF and 18F-PSMA PET/CT at the patient level was observed in 154 patients (96.3%). 18F-PSMA PET/CT tended to identify more bone metastases per patient than 18F-NaF PET/CT. Conclusion: Both 18F-NaF and 18F-PSMA PET/CT exhibit high diagnostic accuracy for detecting bone metastases in newly diagnosed high-risk PC patients. 18F-PSMA PET/CT may detect additional metastatic lesions compared with 18F-NaF PET/CT. Subsequent 18F-NaF PET/CT may be redundant if no bone metastases are found on 18F-PSMA PET/CT.