Search Results (167)

Background: Considering the high global frequency of prostate cancer, it is necessary to know the benefits and drawbacks of numerous diagnostic and therapeutic modalities. Methods: In this article, we include 88 manuscripts (46/88 original studies) found on PubMed, written in English in extenso, dealing with nuclear medicine methods in patients with prostate cancer. Results: Choline PET/CT had low sensitivity in detecting the primary tumor. This method has been almost completely replaced by PSMA PET/CT, which is included in international guidelines and recommended for initial staging of unfavorable intermediate- to high-risk prostate cancer, the detection of recurrent disease after treatment, the evaluation of mCRPC, therapy response evaluation, and theranostics. FDG is currently used in aggressive forms of prostate cancer and as a supplement in PSMA PET/CT for patient selection for RLT. Na[¹⁸F]F has demonstrated satisfactory diagnostic capacity for evaluating bone loss; however, due to a lack of research, it is not recommended in international guidelines. ¹⁸F-Fluciclovine has lower sensitivity than [¹⁸F]F-PSMA-1007 for the detection of early biochemical recurrence in prostate cancer. GRPR and SSTR analogs are less frequently used but can be useful in the evaluation of rarer pathohistological types. [^99mTc]Tc-PSMA can be used in resource-limited settings where PET/CT is unavailable, with a lower sensitivity compared to [¹⁸F]F-PSMA-1007 but a higher sensitivity compared to bone scans. Conclusions: PSMA tracers are important tools for evaluating intermediate- and high-risk prostate cancer, with limitations in 5–10% of prostate cancers that do not express PSMA. Theranostics are increasingly incorporating PSMA. Full article

Background: Approximately half of prostate cancer (PCa) patients present with low- or intermediate-risk disease eligible for active surveillance (AS). However, a substantial proportion of individuals experience pathological progression during follow-up. In this study, we developed predictive models for histopathological PCa progression in patients on AS. Methods: The dataset comprised patients with biopsy-confirmed PCa and a minimum follow-up of two years. All patients underwent regular surveillance, including prostate-specific antigen (PSA) measurements and MRI examinations. Each patient had three to six consecutive MRI scans available for analysis. Histopathological progression was defined as an upgrade to a higher grade group on repeat targeted biopsy. Predictive modeling integrated radiomic and clinical variables using machine learning (ML). SHapley Additive exPlanations (SHAP) was used for feature interpretation. Results: Three models were obtained: (1) a baseline model utilizing radiomic features from initial MRI scans combined with baseline PSA density (PSAd) (AUC = 0.793, sensitivity = 0.690, specificity = 0.830); (2) a delta model incorporating feature changes between latest and baseline available MRI scans with final PSAd (AUC = 0.913, sensitivity = 0.793, specificity = 0.936); and (3) a time series model analyzing the complete series of radiomic features and PSAd (AUC = 0.917, sensitivity = 0.828, specificity = 0.894). Conclusions: Our predictive models demonstrated strong performance in distinguishing progressors from non-progressors, suggesting that radiomic analysis combined with ML has significant potential to enhance PCa management. This approach could enable more personalized treatment strategies and improve clinical decision-making for patients undergoing AS. Full article

Background/Objective: Biochemical recurrence (BCR) after radical prostatectomy (RP) for prostate cancer indicates disease progression. Although type 2 diabetes mellitus (T2D) shows a paradoxical association with prostate cancer risk, the prognostic role of T2D-related genetic variants remains unclear. Methods: We analyzed 113 common T2D susceptibility-related single-nucleotide polymorphisms (SNPs) in 644 Taiwanese men with localized prostate cancer (D’Amico risk classification: 12% low, 34% intermediate, and 54% high) treated with RP. Associations between SNPs and BCR were assessed using Cox regression, adjusting for key clinicopathological factors. Functional annotation was performed using HaploReg and FIVEx, while The Cancer Genome Atlas transcriptomic data were analyzed for C2 calcium-dependent domain-containing 4A (C2CD4A) expression. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were applied to explore related biological pathways. Results: C2CD4A SNP rs4502156 was independently associated with a reduced risk of BCR (hazard ratio = 0.80, p = 0.035). The protective C allele correlated with higher C2CD4A expression. Low C2CD4A expression is associated with advanced pathological stages, higher Gleason scores, and disease progression. GSEA revealed negative enrichment of mitotic and chromatid segregation pathways in high-C2CD4A-expressing tumors, with E2F targets being the most suppressed. GSVA confirmed an inverse correlation between C2CD4A expression and E2F pathway activity, with CDKN2C as a co-expressed functional gene. Conclusions: The T2D-related variant rs4502156 in C2CD4A independently predicts a lower risk of BCR, potentially via suppression of the E2F pathway, and may serve as a germline biomarker for postoperative risk stratification. Full article

Background & Objectives: Current guidelines recognize a subgroup of favorable intermediate-risk (FIR) ISUP grade group (GG) 2 prostate cancer (PCa) that may be eligible for active surveillance (AS). However, upgrading and upstaging to more aggressive disease are frequently observed. We aimed to identify risk factors for adverse pathology in this cohort to better define clinical scenarios where AS may need to be reconsidered. Methods: We retrospectively analyzed 170 patients diagnosed with ISUP GG2 PCa by multiparametric MRI (mpMRI)/TRUS fusion biopsy, all treated with radical prostatectomy (RP). Patients with FIR disease were evaluated for upstaging to ≥pT3 or upgrading to ISUP GG of ≥3 at RP. Multivariable logistic regression identified predictors of adverse pathology. Key Findings and Limitations: Among 170 FIR patients, median PSA was 5.6 ng/mL. Most had PI-RADS 4 (57%) or 5 (20%) lesions; 13% were diagnosed by systematic biopsy only. At RP, 28% showed adverse pathology, including 5 patients (2.9%) with lymph node metastases. Independent predictors were a PI-RADS Score of ≥4, PSA of >7 ng/mL, and clinical T-stage on digital rectal examination. Conclusions and Clinical Implications: Nearly 1/3 of FIR PCa patients were upstaged to high-risk PCa at RP. Based on these findings, AS in clinical practice should only be considered after thorough patient counseling and performed using a stringent follow-up and staging regimen to minimize the risk of further disease progression. A key limitation is the lack of the percentage of Gleason pattern 4. Full article

Background/Objectives: Whole-gland surgery or radiotherapy for localized prostate cancer (PCa) can cure the disease but often impair urinary and sexual function. Focal therapy with high-intensity focused ultrasound (HIFU) seeks to eradicate the tumor while sparing uninvolved tissue. We prospectively evaluated oncological control, functional outcomes and safety of MRI-guided focal HIFU in patients with low- or intermediate-risk PCa. Methods: In this prospective, single-arm, phase II feasibility trial (three Austrian centres, 2021–2024), treatment-naive patients with D’Amico low/intermediate-risk, PSA ≤ 15 ng/mL, clinical stage ≤ T2 and MRI-targeted, biopsy-confirmed index lesions underwent lesion-targeted HIFU (Focal One™). The primary endpoint was failure-free survival (FFS: absence of salvage whole-gland or systemic therapy, metastasis or PCa-specific death). Secondary endpoints included biopsy-proven cancer, prostate-specific antigen (PSA), patient-reported symptoms as International Prostate Symptom Score (IPSS), 5-item International Index of Erectile Function (IIEF), Gaudenz Incontinence Questionnaire and adverse events. Planned follow-up was 24 months with PSA every 3 months, mpMRI and biopsies at 12 months, and imaging- or PSA-triggered biopsies thereafter. Results: Fifty-one men were analysed in the per-protocol cohort (median age 67 years, median PSA 7.55 ng/mL). Median treated volume was 12 mL; median procedure time 85 min. At 24 months, FFS was 94.1%: 3/51 patients (5.9%) required salvage radiotherapy. Among 31 patients who underwent follow-up biopsy, 26 (83.9%) had no cancer; the five positives included three ISUP 1, one ISUP2 and one ISUP 4 lesion. Mean PSA fell by 69% at 3 months (to 2.3 ng/mL) and then stabilized under 3 ng/mL, with a mean of 2.7 ± 1.5 ng/mL at 24 months. Transient acute urinary retention occurred in 11/51 (21.6%); no Clavien–Dindo grade ≥ 4 events were reported. IPSS returned to or improved beyond baseline, erectile function largely recovered by 6–12 months, and only one new case of grade 2 incontinence was observed. Conclusions: MRI-guided focal HIFU achieved high two-year failure-free survival with low morbidity and preserved quality of life in carefully selected patients with low- or intermediate-risk PCa. These data support further randomized and longer-term investigations of focal HIFU as an organ-sparing alternative to whole-gland treatment. Full article

Background and Objectives: Ultra-hypofractionated radiotherapy (uhRT) is increasingly used for low- and intermediate-risk localized prostate cancer, necessitating exceptional precision compared to conventional fractionation. CBCT-based online-adaptive uhRT may help mitigate pelvic organ motion but has not yet been established in clinical routine. We report initial clinical experiences focusing on the feasibility and technical aspects of treatment delivery. Materials and Methods: Seven patients (35 fractions) with low- or intermediate-risk prostate cancer were treated with online-adaptive uhRT on the Varian Ethos^® system within routine clinical care. The target included the prostate and proximal seminal vesicles (CTV1, 5 × 7.25 Gy), with an integrated boost to the prostate (CTV2, 5 × 8.00 Gy). For each fraction, dose–volume histogram (DVH) parameters for targets and organs at risk (OARs) were recorded retrospectively for both scheduled and adaptive plans, along with the plan selection decision. Plan quality was evaluated per clinical DVH constraints and target coverage. The treatment time was recorded. Results: Online-adaptive uhRT was successfully delivered every day in 5 patients and on alternate days in 2 patients. Mean treatment time was 30:17 (±05:49 SD) minutes per fraction. The median recorded change in target and OAR volumes was <10%. Adaptive plans resulted in a statistically significantly improved target coverage for CTV1 (V100%, p = 0.01), PTV1 (D98%, p < 0.001), PTV2 boost (D98%, p < 0.001) in Wilcoxon signed-rank tests. OAR dose reduction was limited, with a small improvement in bladder V40Gy (p = 0.02). Adaptive plans were applied in 32/35 fractions (91.4%). To encompass intra-fractional motion in 95% of fractions, positional adjustments up to 0.77 cm (longitudinal), 0.37 cm (lateral), and 0.59 cm (sagittal) were required. Conclusions: Online-adaptive uhRT appears feasible, leading to optimized target volume coverage. Considerable treatment times must be taken into account. A second CBCT is recommended to compensate for intra-fractional motion. Further research regarding patient-related endpoints and cost-effectiveness is highly needed. Full article

Importance: Understanding trends in the use of hormonal therapy (HT) for prostate cancer (PCa) is crucial to optimize treatment strategies, particularly for older men with locally advanced and metastatic disease. Objective: To evaluate changes in the patterns of adjuvant and primary HT use over time in older U.S. men diagnosed with locally advanced and metastatic prostate cancer. Design, Setting, and Participants: This cohort study utilized SEER-Medicare data, which covers approximately 48% of the U.S. population and links cancer registry data with Medicare claims, including 149,515 men aged ≥66 years diagnosed with PCa between 2010 and 2019. We analyzed trends in the use of adjuvant HT for higher-risk and primary HT for lower-risk PCa. Multivariable logistic regression models were used to adjust for clinical and demographic factors. Main Outcomes and Measures: The primary outcome was the proportion of men receiving any form of HT within 6 months of PCa diagnosis. HT included injectable Gonadotropin-releasing hormone (GnRH) agonists and antagonists, orchiectomy, and anti-androgens agents. Results: The rate of adjuvant HT in higher-risk PCa patients increased significantly from 53.6% in 2010 to 68.1% in 2019 (p < 0.0001), with a steady rise in the last four years. In contrast, the rate of men with lower-risk disease receiving primary HT declined from 25% in 2010 to 16.9% in 2013, then peaked at 28.2% in 2015, and stabilized between 25% and 27.3% from 2017 to 2019. The overall HT usage increased from 33.5% in 2010 to 45.2% in 2019, showing a consistent increase over the years. These patterns persisted after adjusting for clinical and demographic factors. Conclusions and Relevance: The increasing use of adjuvant HT in higher-risk PCa patients aligns with evolving treatment guidelines, while the stable rate of primary HT in lower-risk patients represents persistent inappropriate use and highlights the need for further efforts to optimize treatment choices. While previous studies focused on men with intermediate-risk PCa receiving radiation therapy, our study broadens the scope to include men who did not undergo radiation therapy, providing a more inclusive view of HT trends. Future research should focus on refining strategies to reduce inappropriate primary HT use and improve adjuvant HT administration. Full article

Background/Objectives: Carbon-ion radiotherapy (CIRT) offers precise dose distribution and enhanced biological effectiveness in localized prostate cancer. However, the safety of CIRT in patients with a history of surgery for benign prostatic hyperplasia (BPH), such as transurethral resection of the prostate (TURP), remains unclear. This study aimed to evaluate the long-term safety and oncological outcomes of CIRT in this population. Methods: A retrospective analysis was conducted in 74 of 3848 patients with prostate cancer and a history of surgery for BPH who underwent CIRT combined with risk-adapted androgen deprivation therapy between 2007 and 2023. Adverse events were assessed using CTCAE v5.0. Biochemical recurrence-free survival was estimated using the Kaplan–Meier method and risk factors for hematuria with multivariate logistic regression and receiver operation characteristic (ROC) analysis. Results: CIRT was generally well-tolerated. Early Grade 2 genitourinary (GU) adverse events occurred in 5.4% of patients, and late-Grade 2 or higher GU events occurred in 8.1%. The cumulative incidence of Grade 2 ≥ GU events remained 10% at 36 months. Compared to holmium laser enucleation of the prostate, a shorter interval between BPH surgery and CIRT initiation and a history of TURP were independently associated with an increased risk of hematuria. Notably, 5-year bRFS was 100% in low- and intermediate-risk groups and 88.6% in the high-risk group. Conclusions: CIRT demonstrates acceptable oncological outcomes and urinary complication rates in patients with prostate cancer and a history of BPH surgery. These findings suggest that CIRT can be a feasible treatment option in this surgically altered population, but careful patient selection, individualized treatment planning, and long-term follow-up are essential. Given the absence of a non-BPH control group, oncological efficacy should be interpreted with caution. Full article

Background and objective: Minimally invasive interventions, including irreversible electroporation (IRE), cryoablation, and high-intensity focused ultrasound (HIFU), offer promising alternatives for the treatment of low- and intermediate-risk prostate cancer. We aimed to evaluate the oncological efficacy and safety of these treatments. Methods: A systematic search of MEDLINE, Central, and EMBASE was conducted up to 5 January 2025, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Recurrence, complication, survival, biochemical, and retreatment rates were evaluated, with risk of bias assessed using the Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) and Risk of Bias 2 (RoB2) tools. Results: 85 studies met the inclusion criteria, comprising 42 prospective cohort studies, 36 retrospective cohort studies, six registries, and one randomized controlled trial. Whole-gland HIFU showed significantly lower recurrence (15%) and postoperative mean PSA levels (0.68 ng/mL) than focal HIFU (24%, 2.81 ng/mL). Recurrence rates were similar for focal vs. extended IRE (30% vs. 26%) and focal vs. whole-gland cryoablation (18% vs. 13%). In-field and out-of-field recurrence rates were similar across treatment modalities (5–15%). Retreatment rates were low, with 6–7% of patients receiving a second ablation and 2–8% progressing to radical or hormonal therapy. Major complications were consistently rare. One-year biochemical recurrence-free survival (BRFS) exceeded 95%, and five-year BRFS approached 80% for HIFU and cryoablation. Conclusions: Minimally invasive focal and whole-gland therapies are safe and effective for treating low- and intermediate-risk prostate cancer, with high survival and low major complication rates. Notably, whole-gland HIFU achieves superior biochemical control and lower recurrence than focal HIFU, emphasizing the clinical importance of treatment extent. Full article

Background: To compare the costs of open retropubic radical prostatectomy (RRP), robotic-assisted radical prostatectomy (RALP), intensity-modulated radiation therapy (IMRT), low-dose brachytherapy (LDBT), stereotactic body radiotherapy (SBRT), cryotherapy (Cryo), and high-intensity focused ultrasound (HIFU) for low/intermediate-risk prostate cancer (PCa), from the healthcare system perspective. Methods: This retrospective, IRB-approved study compared the costs and charges of primary treatment options for localized PCa at Duke University Hospital between January 2018 and December 2019. We identified cases by querying the relevant disease, procedural, and charge codes from Duke Finance. Consecutive cases with NCCN high-risk disease, prior treatment, or missing institutional financial information were excluded. Costs were calculated from the point at which the treatment option was selected until the last treatment session (SBRT and IMRT) or hospital discharge (other modalities). All modalities except RRP were considered technology-intensive. Results: A total of 552 patients with a mean age of 65.0 years met the inclusion criteria. NCCN risk categories included 85 (13%) low, 218 (41%) favorable-intermediate, and 249 (46%) unfavorable-intermediate risk cases. RALP, RRP, Cryo, and HIFU were single-session treatments, whereas IMRT, SBRT, and LDBT were delivered over multiple sessions. IMRT and SBRT were the most expensive modalities, followed by RALP, HIFU, LDBT, Cryo, and RRP. The number of sessions (ρ = 0.55, p < 0.001) and being technology-intensive (ρ = 0.58, p < 0.001) were significantly correlated with treatment costs. Conclusions: In this cohort of PCa patients, treatment costs were highest for IMRT and SBRT, followed by RALP, HIFU, LDBT, Cryo, and RRP. The number of treatment sessions was a significant predictor of higher costs. Full article

Background: In the evolving landscape of localized prostate cancer management, focal therapies such as high-intensity focused ultrasound (HIFU) and prostate gland cryoablation (PGC) have emerged as organ-sparing alternatives for patients with low- to intermediate-risk disease. While these strategies aim to preserve functional outcomes, comparative data against robot-assisted radical prostatectomy (RARP) remain scarce and heterogeneous. Methods: We conducted a prospective, single-center study evaluating oncologic and functional outcomes in patients with organ-confined prostate cancer (Grade Group ≤ 2) treated with HIFU (n = 49), PGC (n = 114), or RARP (n = 109). Outcomes were assessed using standardized definitions at a median follow-up of 22 months. Treatment failure was defined according to EAU guidelines, and Kaplan–Meier analysis was applied to time-to-event outcomes. Results: Focal therapy patients were older, more comorbid, and had lower baseline erectile function (each p < 0.001). RARP was associated with the longest operative time but yielded the lowest complication rate (2.75% vs. 20.4% for HIFU and 31.5% for PGC; p < 0.001). Catheter-related morbidity was disproportionately higher in the PGC group. RARP conferred a longer time to treatment failure (p < 0.001), although continence and potency recovery at follow-up were comparable across groups. Notably, erectile function returned earlier among HIFU patients. Conclusions: While focal therapies offer promising early functional results with minimal perioperative risk, they are associated with earlier treatment failure and higher catheter-related morbidity, particularly after cryoablation. These findings underscore the need for individualized treatment strategies guided by standardized, comparative outcome frameworks. Full article

Purpose: This study evaluates the combined prognostic value of the apparent diffusion coefficient (ADC) from multiparametric MRI (mpMRI) and prostate-specific antigen (PSA) levels at 6 months post-radiotherapy (RT) in assessing treatment response in prostate cancer patients treated with RT and androgen deprivation therapy (ADT). Materials and Methods: All prostate cancer patients classified as unfavorable intermediate-risk, high-risk, or very high-risk, according to NCCN criteria, who received ADT and RT between 2008 and 2019 and underwent mpMRI and PSA testing 6 months after RT were included. Patients were stratified into three profiles based on threshold PSA (≤ vs. >0.1 ng/mL) levels and ADC (≤ vs. >1.24 × 10⁻³ mm²/s) values: Profile A: low PSA and high ADC; Profile B: either high PSA/high ADC or low ADC/low PSA; Profile C: high PSA and low ADC. Ten-year progression-free survival (PFS) and metastasis-free survival (MFS) were analyzed using Kaplan–Meier curves and multivariate Cox regression. Results: Ninety-eight consecutive patients were retrospectively analyzed, of which 73 (74.5%) were high-risk. After a mean follow-up of 95.3 months, 19 (19.39%) patients progressed. Ten-year PFS, MFS, and overall survival were 75.6%, 87%, and 89.5% respectively. Progression events were 9.1% (Profile A), 29.4% (Profile B), and 44.4% (Profile C). Eight-year PFS was 89.2% (profile A), 70.9% (profile B) HR: 3.021 (CI 95%: 1.031–8.849; p = 0.044) and 44.4% (profile C) HR: 6.145 (CI 95%: 1.645–22.955; p = 0.007). Multivariate analysis confirmed a higher risk of progression in patients from profile B with HR: 3.958 (CI 95%: 1.18–13.191; p = 0.025) and profile C with HR: 41.945 (CI 95%: 5.000–351.761; p < 0.001) compared to patients from profile A. Metastasis events were 5.5% (Profile A), 8.8% (Profile B), and 33.3% (Profile C). Eight-year MFS was 100% (profile A), 89.6% (profile B) HR: 1.373 (CI 95%: 0.277–6.811; p = 0.689), and 74.1% (profile C) HR: 5.566 (CI 95%: 1.119–27.692; p = 0.047). Conclusions: The integration of PSA response and ADC measures at 6 months post-RT provides an effective combined prognostic factor to identify patients at higher risk of relapse, supporting closer monitoring and potential treatment intensification. Full article

Background/Objectives: Since the proPSMA trial, prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scan has primarily replaced conventional imaging for staging newly diagnosed prostate cancer. The objective of this commentary is to summarise the existing literature on the role of PSMA PET in staging favourable intermediate-risk prostate cancer. Methods: A literature search was conducted on Embase and Ovid MEDLINE, and three retrospective cohort studies were identified. Results: Overall, these studies demonstrated a low prevalence of nodal and distant metastases, as well as modest diagnostic performance of PSMA positron emission tomography-computed tomography (PET-CT) in this patient group. Additionally, PSMA PET did not significantly outperform existing nomograms in predicting lymph node involvement. Conclusions: Given its limited sensitivity, low yield, and cost, the routine use of PSMA PET-CT in favourable intermediate-risk prostate cancer patients is not recommended. Further prospective studies and cost-effectiveness analyses are warranted to clarify its role in this population. Full article

Background and Objective: Adverse pathology to high-risk prostate cancer (PCa) after radical prostatectomy (upgrading) poses a threat to risk stratification and treatment planning. The impact on sexual function, urinary continence, and health-related quality of life (HRQOL) remains unclear. Methods: From 2004 to 2024, 4189 patients with preop low-/intermediate-risk PCa (Gleason score 6 or 7a, PSA ≤ 20 ng/mL) underwent radical prostatectomy at our department and were analyzed. Primary endpoint was HRQOL, erectile function, and urinary continence. Secondary endpoint was rate of salvage therapies and biochemical-free survival. Propensity score matching was performed using “operative time”, “robot-assisted surgery”, “blood loss”, “nerve-sparing surgery”, “age”, and “BMI” to represent comparable surgical approach. Median follow-up was 39 months (Interquartile-range (IQR) 15–60). Key Findings and Limitations: Patients who were upgraded to high-risk PCa showed a higher rate of postoperative radiotherapy and androgen-deprivation therapy compared to patients who were not upgraded (21% vs. 7%, p < 0.001; 9% vs. 3%, p = 0.002). Five-year biochemical recurrence-free survival was 68% in the upgrading group vs. 84% in the no-upgrading group (p < 0.001). We saw no difference in patient-reported HRQOL, urinary continence, or erectile function. Multivariable analysis showed that postoperative upgrading was a significant risk for not achieving good overall HRQOL (OR: 0.77, 95% CI: 0.61–0.97, p = 0.028) during the follow-up. Conclusions and Clinical Implications: Although postoperative upgrading to high-risk PCa leads to worse oncologic outcomes and higher salvage therapy rates, this study indicates that its impact on health-related quality of life is minimal and should not deter a cautious approach to radical prostatectomy. Full article