Prediction of tumor control probability in prostate cancer radiotherapy using a biophysical model incorporating cancer stem cell and hypoxia.

This study aimed to externally validate the European Association of Urology (EAU) biochemical recurrence (BCR) risk stratification in a North American population after radical prostatectomy (RP) and radiation therapy (RT), where validation remains lacking despite prior European and Asian validation. We identified all patients with BCR after RP or RT between 1995 and 2023 from a North American institutional database and classified them by EAU criteria. Primary outcome was prostate cancer-specific mortality (CSM). We calculated Harrell's concordance indices (C-index) and used competing-risk regression to assess associations between EAU risk groups and CSM, comparing performance to multivariable models including age, clinical stage, Gleason grade, PSA doubling time and time to BCR. Among the 940 patients (646 RP, 294 RT; 40.5% African American), 563 (59.9%) had low-risk and 377 (40.1%) high-risk BCR. The 10-year cumulative incidence of CSM was 3.6% versus 12% for low-risk versus high-risk RP patients and 18.4% versus 49.5% for low-risk versus high-risk RT patients. EAU high-risk BCR was associated with increased CSM in both groups (RP: HR 2.83, 95% CI 1.47-5.46; RT: HR 3.98, 95% CI 2.43-6.53). The EAU classification showed moderate discrimination (Harrell's C-index 0.62 for RP, 0.69 for RT). Multivariable models including clinical variables demonstrated a Harrell's C-index of 0.76 for both RP and RT. This first North American validation confirms moderate EAU discriminative ability. For RP patients, low 10-year CSM in low-risk BCR (3.6%) supports surveillance. However, low-risk RT BCR showed substantial CSM (18.4%), exceeding high-risk RP (12%), suggesting current criteria inadequately stratify risk after RT.

Oncological outcomes following PSMA PET/CT-guided salvage whole-pelvis radiotherapy for recurrent prostate cancer.

Maximizing diagnostic yield: A systematic review and deep dive into PSMA PET scan protocol variations for prostate cancer.

Dynamic risk stratification (DRS) enables response-adapted follow-up in differentiated thyroid carcinoma (DTC). However, prospective data supporting surveillance de-escalation and discharge to primary care (PC) after an excellent response (ER) is lacking. We conducted a longitudinal cohort study with a prospectively conducted postdischarge reassessment, including 154 patients with DTC treated with total thyroidectomy, with or without radioiodine ablation, who completed ≥5 years of specialist follow-up and were discharged to PC after achieving ER. A small subset (n = 9) of clinically stable patients was also discharged despite a persistent indeterminate response (IR), based on clinical judgment. Patients underwent a standardized reassessment ≥5 years after discharge to PC. DRS was assessed at three predefined time points 6 months after initial therapy, final predischarge specialist visit, and postdischarge reassessment. Outcomes included recurrence, additional interventions, real-world PC follow-up practices, referrals back to specialist care, and patient-reported outcomes collected at reassessment using a study-specific 5-point Likert-type questionnaire. Baseline American Thyroid Association-2025 recurrence risk was low 78/154 (50.6%), intermediate-low 44/154 (28.6%), intermediate-high 23/154 (14.9%), and high 9/154 (5.8%). ER increased from 118/154 (76.6%) at 6 months to 145/154 (94.2%) at predischarge and to 148/154 (96.1%) at postdischarge reassessment (p < 0.001). At last predischarge visit, 9/154 (5.8%) had an IR, decreasing to 6/154 (3.9%) at postdischarge reassessment. No biochemical or structural recurrences were observed over a mean postdischarge follow-up of 70.3 ± 10.6 months. All non-ER findings at reassessment occurred exclusively in patients already classified as IR at discharge, with no deterioration from ER. During specialist follow-up, 8/154 (5.2%) required additional interventions. PC surveillance was characterized by low-intensity follow-up, with thyroglobulin testing in 11/154 (7.1%), no routine neck ultrasound, and stable levothyroxine dosing. Premature re-referral to specialist care occurred in 13/154 (8.4%) without evidence of recurrence. Despite favorable outcomes, 66/154 (42.9%) reported high fear of recurrence and 141/154 (91.6%) preferred specialist follow-up. Our findings suggest that patients with DTC who complete ≥5 years of specialist follow-up and achieve ER may be safely transitioned to PC. ER represents a stable clinical state, with minimal risk of clinically meaningful recurrence even with markedly reduced biochemical and imaging surveillance. These findings support a response-adapted long-term care model centered in PC, focused on thyroid hormone replacement and TSH monitoring. Further studies are warranted to confirm these findings.

Prostate-specific membrane antigen-positron emission tomography (PSMA-PET) is guideline recommended across multiple clinical scenarios, but the real-world adoption and performance characteristics of this novel technology remain underreported. Patients undergoing PSMA-PET imaging in either primary staging or postprostatectomy settings were reviewed within the Michigan Urological Surgery Improvement Collaborative data registry. Adoption over time and rates of positive findings by location and risk group at diagnosis (staging setting) or PSA level at the time of scan (postprostatectomy setting) were tabulated. Staging PSMA-PET findings were compared with pelvic lymph node dissection yield and characteristics associated with false-negative PSMA-PET were explored. The study cohort comprised 2433 PSMA-PET scans among 2342 patients. Adoption increased over the study period-up to 46% of high-risk patients underwent staging PSMA-PET by 2024. Positive and negative predictive values for pelvic lymph node pathology were 21.1% and 92.0%, respectively. Patients with positive lymph node pathology despite negative PSMA-PET had higher Gleason grade (P = .034) and pT stage (P < .001) compared with patients with negative imaging and pathology. In total, 58.1% of scans were positive in the postprostatectomy setting, with significant rates of positive imaging findings seen at low PSA values (32% among patients with PSA < 0.2 ng/mL at the time of imaging). PSMA-PET has seen widespread adoption; real-world performance characteristics show modest divergence from those reported in clinical trials. Further work will more directly assess the impact of this novel imaging modality on patient management.

The introduction of the drop-in gamma probe has advanced intraoperative molecular imaging during prostate cancer surgery. We have been able to convert the sensor's numeric readout to tomographic images, so-called robotic-SPECT (RoboSPECT) and investigate how this is impacted by radiopharmaceutical avidities and drop-in scan metrics. The gamma sensor readout was registered with its 3D position and orientation, allowing a custom reconstruction algorithm to generate RoboSPECT images. Evaluations occurred in 21 patients; 10 sentinel node procedures (SN; primary prostate cancer) and 11 PSMA-radioguided surgery (recurrent prostate cancer). RoboSPECT findings were related to respective pre- and intra-operative controls, including preoperative PSMA-PET/CT and/or SPECT/CT images and fluorescence detection (SN only). RoboSPECT proved to be safe and applicable in a range of conditions. In the SN-group, 26 SN-SPECT/CT lesions were successfully identified with SN-RoboSPECT (100%); 3 were tumor positive (sensitivity 100%). Only 73% of SNs were surgically visible with fluorescence imaging. For the PSMA guided group, the 14 lesions identified on PSMA-PET/CT were all visualized with PSMA-RoboSPECT (100%); 18 specimens were tumor positive (sensitivity 78% for both PSMA-PET/CT and PSMA-RoboSPECT). Preoperative PSMA-SPECT/CT only identified 4 PSMA-lesions (29%). No false positives were seen for roboSPECT and all final resection margins were clean. At 6-months 0% of the SN-patients and 20% of PSMA-patients showed biochemical recurrence. RoboSPECT provides 3D context that extends the utility of drop-in gamma tracing and assists the alignment between pre- and intra-operative target perception. Here SN-RoboSPECT clearly outperformed fluorescence SN imaging and PSMA-RoboSPECT outperformed preoperative PSMA-SPECT/CT imaging.

Zirconium-89-based PSMA PET/CT with delayed imaging for early detection of biochemical recurrence in prostate cancer patients with PSA ≤ 0.2 ng/mL: A feasibility study.

Port site metastasis is an uncommon but clinically relevant complication, particularly associated with minimally invasive surgery for abdomino-pelvic malignancies, often indicating poor prognosis and necessitating prompt evaluation for potential surgical intervention. Proposed mechanisms include direct tumor implantation, aerosolization during pneumoperitoneum, surgical wound contamination, and immune alterations. In this report, we describe a case of a 48-year-old man who developed SSTR-expressing port site metastases, occurring 4 years and 4 months following laparoscopic resection of an ileal neuroendocrine tumor (NET). This case highlights the importance of long-term SSTR-based PET imaging surveillance in NET patients following minimally invasive surgery, even in the absence of symptoms or early biochemical relapse.

Prostate-specific membrane antigen (PSMA) PET/CT is routinely used to restage prostate cancer (PCa) in patients with biochemical recurrence (BCR), yet negative scans may still harbor subclinical disease. This study investigated whether radiomics features extracted from recurrence-prone organs on negative [¹⁸F]DCFPyL PET/CT can predict clinical progression (CP) and clinical progression-free survival (CPFS).&#xD;Materials and Methods: We performed a post-hoc analysis of 132 patients with BCR (mean age, 74.5 years) who had negative [¹⁸F]DCFPyL PET/CT scans and received no further treatment after imaging. Recurrence-prone organs, defined as anatomical sites at highest risk for prostate cancer recurrence (prostate bed, lymph nodes, bones, liver, and lungs), were segmented using nnU-Net (TotalSegmentator), and radiomics features were extracted. Machine learning models (XGBoost) and Cox proportional hazards models were evaluated using nested cross-validation (5-fold outer, 3-fold inner). External validation across two independent centers was performed after ComBat harmonization. The effect of reader-assigned diagnostic certainty on predictive performance was also examined. Only recurrence-prone organs were analyzed, as prior studies have shown that more than 80% of PCa recurrences arise in these regions.&#xD;Results: Median PSA at imaging was 0.74 ng/mL. During a median follow-up of 25.5 months, 42 of 132 patients (31.8%) developed progression. The concordance index improved from 0.65 using clinical variables alone to 0.74 when PET, CT, and clinical features were combined (p < 0.05). Predictive performance was strongly influenced by diagnostic certainty, with moderate-certainty negative scans showing higher accuracy than high-certainty negative scans. Radiomics features derived from negative PSMA PET/CT reflected systemic recurrence risk and were associated with early lung metastases. External validation demonstrated less than 10% reduction in performance despite inter-center differences.&#xD;Conclusion: Radiomics signatures from recurrence-prone organs on negative PSMA PET/CT may reveal subclinical disease and provide complementary biomarkers for risk stratification in BCR patients.

Prostate cancer (PCa) is the second most common cancer and cause of cancer deaths among American men. Existing risk prediction methods have limited accuracy and reproducibility, resulting in difficulty in predicting treatment outcomes. We demonstrate the development and external validation of an automated multimodal artificial intelligence (AI) algorithm using biparametric magnetic resonance imaging (bpMRI) and clinical covariates for predicting biochemical recurrence (BCR) after radical prostatectomy (RP) in patients with PCa. The development cohort included 80% of patients from center 1 (n = 240) who underwent prostate MRI prior to RP between January 2008 and December 2018, with a minimum of 2 years of follow-up after RP. The test cohort included the remaining 20% of center 1 patients (n = 71) and an external validation cohort from center 2 (n = 168). Center 2 patients included those who underwent prostate MRI and RP between January 2015 and January 2024, with a minimum of 2 years of follow-up. Clinical comparisons were made using the Cancer of the Prostate Risk Assessment Postsurgical (center 1) and International Society of Urological Pathology Gleason Grade Group (ISUP GGG) scoring systems from post-RP pathology (center 2). The models developed were as follows: clinical (M0), automated clinical (M1), radiomics (M2), and a multimodal model (M3). Clinical variables (M0) included prostate-specific antigen (PSA), age, primary Gleason, and ISUP GGG. Automated clinical variables (M1 and M3) included PSA and age. Radiomic features (M2 and M3) were extracted from bpMRI using a lesion detection AI model. Accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated, and log-rank tests compared BCR-free survival to assess the models' ability to discriminate relative to clinical standards. Intermediate-risk groups were also assessed. The multimodal model (M3) had the highest AUC across test sets (combined: 0.71; center 1: 0.70; center 2: 0.75). This was the only model that significantly differentiated BCR-free survival outcomes in intermediate-risk groups across both centers (P < 0.05). This automated multimodal model leveraging radiomics and clinical covariates can predict BCR after RP, approaching clinical gold standards, and may enhance imaging-based prognostication following further validation. Given that this model demonstrated the potential to outperform pre-surgical and post-surgical clinical gold standards in an external cohort's intermediate-risk patient subgroup (for whom it is more challenging to predict disease trajectory), this model may contribute to enhanced personalized care in PCa after further validation.

SAKK 09/10: dose-intensified salvage radiotherapy for biochemical recurrence after prostatectomy-no benefit, but additional toxicity?

We investigated the real-world criteria and thresholds physicians use to classify patients with nonmetastatic castration-sensitive prostate cancer with biochemical recurrence as high risk, and how these align with guidelines. Descriptive analyses were conducted using data abstracted from an independent, retrospective, cross-sectional survey completed by urologists and radiation oncologists in the USA between April and November 2023. Physicians provided their perspectives and extracted chart data for the last 6-8patients they diagnosed with high-risk biochemical recurrence. The cohort included 87 physicians (79% urologist, 21% radiation oncologist), who reported data for 460 patients. Physicians believed in using multiple factors for risk stratification, notably prostate-specific antigen doubling time (94%), absolute prostate-specific antigen rise following definitive therapy (89%), and Gleason score (87%). Over half named prostate-specific antigen doubling time as the most important factor. Physicians used a median (interquartile range) prostate-specific antigen doubling time threshold of 6.0 (6.0-9.0) months when identifying patients with high-risk biochemical recurrence. At the patient level, prostate-specific antigen doubling time (58%), Gleason score (44%), and absolute prostate-specific antigen rise following definitive therapy (43%) were the most frequently reported factors used for determining high-risk biochemical recurrence in the real world. Physicians use multiple clinical factors to identify high-risk biochemical recurrence. These factors generally align with guidelines. However, physicians generally used a more restrictive prostate-specific antigen doubling time threshold than many guidelines recommend. Discrepancies present an opportunity for further education, potentially expanding the pool of patients with high-risk biochemical recurrence who may benefit from recent advances in management.

The safety of testosterone therapy (TTh) in men with a history of prostate cancer (PCa) remains controversial, particularly after interventions for PCa including radical prostatectomy (RP). Previous meta-analyses have included heterogeneous populations, limiting interpretation. To systematically review and meta-analyze the risk of biochemical recurrence (BCR) in hypogonadal men treated with TTh following RP for PCa. A systematic search of Medline was conducted from 1969 to July 2025 according to PRISMA and MOOSE guidelines. Studies reporting BCR rates after TTh in men who underwent RP were included. Data were pooled using a random-effects model. Meta-regression explored the associations with age, Gleason score, follow-up, and preoperative prostate specific antigen (PSA). Seven retrospective studies met the inclusion criteria, encompassing 398 patients (mean age: 63.9 years; mean follow-up: 29.6 months). Overall, the pooled BCR rate in TTh-treated patients was 3.5% (95% CI: 1.5-8.5). No significant association was found between BCR and age, Gleason score, or follow-up duration. In studies with untreated controls, TTh was associated with a significantly lower BCR risk. Limited data suggested improvements in erectile function and quality of life. Funnel plot analysis indicated no publication bias. TTh after RP appears to be associated with a limited risk of BCR in hypogonadal men with PCa. However, the absence of randomized controlled trials and incomplete reporting of key clinical variables preclude definitive conclusions. Larger, well-designed prospective studies are warranted to confirm these findings and clarify the long-term safety profile of the use of testosterone replacement therapy in this setting.

This podcast features two of the investigators from the phase III EMBARK trial (NCT02319837) in conversation. The primary results from EMBARK demonstrated meaningfully improved primary and key secondary efficacy outcomes, while maintaining quality of life, with enzalutamide with or without leuprolide versus leuprolide alone in patients with high-risk biochemically recurrent prostate cancer. Notably, there was a meaningful improvement in overall survival with enzalutamide plus leuprolide compared with leuprolide alone. In this third podcast in the EMBARK series, the speakers discuss the key findings from the subsequent (protocol-defined and post hoc) analyses of EMBARK, including clinically relevant secondary outcomes; efficacy endpoints by age, prior definitive therapy, and the definition of high-risk biochemical recurrence per European Association of Urology criteria; and patient-reported outcomes by treatment suspension status. The podcast will predominately focus on the real-world implications of these findings for clinical practice. Clinicaltrials.gov identifier NCT02319837.

This study evaluated if [99mTc]HYNIC-prostate-specific membrane antigen (PSMA)-11 scintigraphy presents a clinically viable imaging alternative to [68Ga]PSMA-11 PET/computed tomography (CT) for disease evaluation in prostate cancer (PC). In this prospective study, 106 patients diagnosed with prostate cancer were recruited. A total of 51 patients were assigned in the initial staging cohort and the remaining 55 patients in the re-staging cohort (comprising biochemical recurrence, metastatic castration-resistant prostate cancer, and metastatic hormone-sensitive prostate cancer). Imaging with [99mTc] HYNIC-PSMA-11 was conducted within one week following [68Ga]PSMA-11 PET/CT. Whole-body planar [99mTc]HYNIC-PSMA-11 images were obtained at 2-, 4-h, and regional SPECT/CT at 3-h. A comparative detection efficiency of [99mTc]HYNIC-PSMA-11 versus [68Ga]PSMA-11 PET/CT was evaluated by consensus for the involved lesions/sites. A correlation analysis was carried out between maximum standardized uptake values of PSMA PET and percent quantitative lesion uptake values of PSMA SPECT. [68Ga]PSMA-11 PET/CT detected 896 metastatic lesions, where HYNIC-PSMA-11 detected 761 lesions, offering an overall sensitivity of 85%. The sensitivity of [99mTc] HYNIC-PSMA-11 SPECT/CT was 100% for primary/visceral lesions, 92% for skeletal lesions, 75.3% for distant lymph nodes and 67.4% for locoregional lymph nodes. A substantial agreement (κ = 0.78, P < 0.0001) was seen between two imaging modalities. UCSF Cancer of the Prostate Risk Assessment score based disease staging matched with the disease staging demonstrated by both the imaging techniques. A significant (P < 0.01) correlation was seen between the quantitative parameters of the two techniques both for primary (r = 0.96) and metastatic (r = 0.79 for skeletal and r = 0.65 for lymph nodes) lesions. [99mTc]HYNIC-PSMA-11 SPECT/CT offers a potentially viable and cost-effective substitute for PSMA-PET for disease staging, quantification and response assessment to PSMA-targeted radiotherapies.

While prostate cancer (PrCa) is highly heritable, the genes associated with PrCa survival after diagnosis remain poorly understood. We aimed to identify genes associated with PrCa-specific survival through transcriptome-wide association studies (TWAS) using genetic predictors of gene expression in the prostate. We used the Transcriptome-Integrated Genetic Association Resource (TIGAR) to train expression prediction models separately using normal prostate, primary tumor, and metastatic tumor tissues. We performed TWAS using these models in data from the Malmö Diet and Cancer (MDC) study (discovery) and Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial (validation). We identified and validated seven genes associated with PrCa-specific survival at a common locus on chromosome 1. We found two genes using prediction models from normal prostate tissues and five with models from metastatic tumor tissues. Elevated RCC1 expression is linked to a shorter time to biochemical recurrence, while higher PHACTR4 expression was observed in tumors with a higher Gleason grade. The study is limited to European ancestry and can only show associations. Further research across other populations and experiments to establish causality will be needed. Our multi-tissue study identified novel genes associated with PrCa survival, particularly RCC1 and PHACTR4, providing new insights for potential genomic markers for PrCa survival.

A 70-year-old man with prostate cancer underwent contrast-enhanced CT for lesion characterization, which revealed two newly detected hepatic lesions suspicious for metastasis. The prostate-specific antigen level remained below the threshold for biochemical recurrence, whereas C-reactive protein was elevated. 18F-FDG PET/CT was performed for metabolic characterization and whole-body evaluation, demonstrating heterogeneous increased uptake in both lesions. On the basis of the CT findings and FDG hypermetabolism, liver-confined metastatic disease was suspected, and surgical resection was performed. Histopathology unexpectedly revealed a hepatic inflammatory pseudotumor.

PSA persistence in the PSMA PET era: reassessing a risk factor after radical prostatectomy.

Urinary incontinence (UI) may persist in some patients after robot-assisted radical prostatectomy (RARP), significantly affecting quality of life (QOL). This study investigated the changes in UI and pelvic floor muscle (PFM) volume in patients with persistent UI after RARP who underwent testosterone replacement therapy (TRT). Patients with persistent UI after RARP who exhibited symptoms of late-onset hypogonadism (LOH) and had no evidence of prostate cancer recurrence received TRT for 6 months. Magnetic stimulation (MS) was additionally performed upon patients' request. Blood tests, 1-h pad test, urinary symptom questionnaires, and muscle mass evaluation were performed before and after TRT. PFM volume was measured by thin-slice computed tomography. Thirty patients were enrolled, 15 of whom received MS in addition to TRT. Pad weight significantly decreased after TRT (mean change ± standard deviation [SD]: -44.1 ± 67.6 g; p = 0.001; 95% confidence interval: -69.3 g, -18.8 g), with no significant difference between the MS and non-MS groups. However, only the MS group showed significant improvements in questionnaire scores (Overactive Bladder Symptom Score: p = 0.045; International Prostate Symptom Score [IPSS]: p = 0.041; IPSS-QOL: p = 0.022) and an increase in PFM volume (mean ± SD: 6.3 ± 4.2 mL, p < 0.001). The increase in PFM volume in the MS group was significantly greater than that in other muscle parameters. No patient showed elevated prostate-specific antigen levels (> 0.2 ng/mL), indicating no biochemical recurrence. TRT was associated with reduced UI after RARP. The combination of TRT and MS may help increase PFM volume and improve urinary symptom questionnaire scores. Further accumulation of evidence is needed to clarify these synergistic effects.