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.

Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer death in men. Acinar adenocarcinoma accounts for 90% of primary prostatic cancers. Carcinoma of the basal cells of the prostate is extremely rare, making up less than 1% of prostate cancer diagnoses. As opposed to adenocarcinoma, basal cell-type carcinoma of the prostate (BCCP) does not usually secrete PSA and most commonly presents with symptoms of typical BPH. Due to its nonspecific symptoms and absence of PSA secretion, it is often diagnosed at the locally advanced stage. In part due to its rarity, there are no standardized treatment protocols. Agent Orange (AO) is a pesticide utilized by the US Military during the Vietnam War, which was contaminated with polychlorinated dibenzo-dioxins (PCDDs). These compounds have been linked to the development of various malignancies, including prostate cancer, although a direct causal relationship remains unproven. We present the case of a US Vietnam Veteran with Agent Orange exposure who was diagnosed with multiple distinct types of prostate cancer, including BCCP. He was initially found to have BCCP on pathological evaluation of prostate tissue from a prostatic resection for BPH. He was treated with definitive radiotherapy. He subsequently developed a recurrence of prostate cancer, but on this occasion, he was found to have localized prostatic adenocarcinoma and was treated with salvage High Intensity-Focused Ultrasound (S-HIFU). He remained without recurrence to the time of the writing of this report, 60 months after undergoing S-HIFU. Upon review of the literature, there is a lack of data regarding the environmental exposures of patients who develop BCCP, as well as a lack of documentation of rare subtypes of prostate cancers that have been identified in AO-exposed Veterans. Further studies on this subject would be beneficial, as there are millions of US veterans alive who had exposure to PCDDs during the Vietnam War and the more recent Global War on Terror.

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

Salvage lymph node dissection in oligo-recurrent prostate cancer patients: Mapping patterns of recurrence and factors associated with disease progression.

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.

Re: Hormone Therapy Use and Duration with Postoperative Radiotherapy for Recurrent Prostate Cancer: an Individual Patient Data Meta-analysis.

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.

Salvage prostatectomy (sRP) is one of several treatment options for localized prostate cancer recurrence after radiation. However, given the complexity of this operation, traditionally high complication rates, and poor functional outcomes, sRP has historically been underutilized. Herein, we aim to review the indications, outcomes, and technical advancements of sRP in modern practice. A literature review was performed using PubMed, Google Scholar, and Scopus for relevant articles that were synthesized in the current work. Improvements in interpretation of magnetic resonance imaging and increased adoption of molecular imaging can better detect local and oligometastatic recurrence. In combination with clinical variables, this can better select patients who may achieve a durable response from sRP. Ten-year biochemical recurrence-free survival after sRP ranges from 28 to 53%, with cancer specific survival ranging from 65 to 83%. While complication rates for sRP are higher than for primary prostatectomy, major complications, especially rectal injury, have decreased significantly. Erectile function is poor after sRP, although most studies report high rates of pre-operative impotence. Continence rates are highly variable (20-80%) secondary to heterogeneous reporting. Due to high rates of lymph node involvement, lymph node dissection should be performed with sRP and has prognostic value. Finally, robotic sRP is gaining popularity and may lead to improvements in continence, although further study is needed. Salvage prostatectomy can achieve durable cancer control in a substantial group of patients. With improving complication rates and functional outcomes in experienced hands, sRP remains an important treatment for radio-recurrent prostate cancer.

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.

18F-PSMA PET/CT and pelvic MRI are useful for assessing biochemical recurrence of prostate cancer after prostatectomy. We evaluated the role of 18F-PSMA PET/MRI in a 1-stop-shop protocol combining a single injection of 18F-PSMA, followed by pelvic PET/multiparametric MRI (mpMRI) and whole-body PET/CT acquisitions for the detection of recurrent disease. Methods: We evaluated 106 consecutive patients referred to our institute for biochemical recurrence after prostatectomy using a 1-stop-shop protocol comprising whole-body 18F-PSMA PET/CT and pelvic 18F-PSMA PET/mpMRI. Each imaging modality was reviewed in a blinded manner by 2 independent, experienced readers. 18F-PSMA PET/MRI, with positivity on either MRI or PSMA PET, served as the reference standard. Results: 18F-PSMA PET/MRI detected more local recurrences (n = 52, 49.06%) compared with 18F-PSMA PET/CT (n = 42, 39.62%) and mpMRI (n = 46, 43.00%). Discordant cases accounted for 18 patients (17%): 10% were positive only on MRI and 7% only on PSMA PET. Compared with 18F-PSMA PET/MRI, both mpMRI and 18F-PSMA PET demonstrated similar performance, with sensitivities of 88.5% and 78.8% and specificities of 100% and 98.1%, respectively. Conclusion: 18F-PSMA PET/MRI outperformed PET/CT and mpMRI in the detection of local recurrences of prostate cancer.

The detection of biochemical recurrence (BCR) of prostate cancer remains challenging, as small-volume disease may fall below the sensitivity of standard imaging. Prostate-specific membrane antigen (PSMA) PET/CT is currently the most sensitive imaging modality for tumor detection at low prostate-specific antigen (PSA) levels, but recurrence continues to be difficult to detect. We evaluated whether routine delayed pelvic imaging at 90 min postinjection improves diagnosis of sites of recurrence in patients referred for BCR. Methods: We retrospectively analyzed 201 patients with prostate cancer undergoing dual-phase 68Ga-PSMA PET/CT for BCR of prostate cancer (median PSA, 0.52 ng/mL). Imaging of vertex to midthighs was acquired at approximately 60 min and delayed pelvic imaging at approximately 90 min postinjection. Two nuclear medicine physicians independently assessed whether delayed imaging improved diagnostic certainty or revealed additional 68Ga-PSMA-avid lesions. Results: Delayed pelvic imaging improved diagnostic certainty for 68 patients (34%) and revealed additional 68Ga-PSMA-avid lesions for 23 patients (11%). Of patients with additional lesions detected on delayed imaging, roughly one third-representing 3% of the total cohort-subsequently received focal radiation dose escalation during treatment planning. Improvements were primarily influenced by increased tracer uptake confirming subtle lesions, reduced bladder or ureteral interference, and differentiation of physiologic from pathologic uptake. All measurable lesions within the field of view of the delayed pelvic image were quantified. The median SUVmax for malignant lesions increased from 4.3 to 5.0, whereas benign lesions remained stable (median SUVmax of 2.7 on normal imaging and 2.6 on delayed imaging). Conclusion: Routine delayed pelvic imaging at 90 min postinjection enhanced lesion detection and diagnostic confidence in BCR of prostate cancer, particularly at low (<1 ng/mL) PSA levels. The addition of this additional acquisition into standard PSMA PET/CT protocols can improve staging accuracy and clinical decision-making.

Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) tracers have reshaped prostate cancer (PC) imaging, supplementing non-PSMA options such as choline-based agents. However, direct comparative performance data across tracers remain scarce, leaving the optimal choice uncertain. We therefore conducted a systematic review and network meta-analysis (NMA) to assess detection rates (DRs) among PET tracers used for primary and biochemically recurrent PC. Following PRISMA-NMA guidelines, we systematically searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov through March 2025 for studies comparing 2 PET tracers for prostate cancer. The primary outcome was DR, defined as the proportion of PET-positive patients or lesions. Two reviewers independently extracted data on study design, patient demographics, and imaging parameters, and evaluated quality with QUADAS-2. We performed frequentist random-effects NMA to calculate relative risks (RRs) with 95% CIs, using 68 Ga-PSMA-11 as reference. Nineteen studies (1681 patients) addressed biochemical recurrence, and 6 (271 patients) targeted primary PC, with 2 overlapping. Risk of bias was low for most domains, though some uncertainty remained for reference standards and timing. In biochemically recurrent PC, PSMA-directed tracers achieved higher DRs than non-PSMA probes. Within the PSMA tracers, 64 Cu-PSMA-617 achieved the highest estimated DR, followed by 18 F-DCFPyL, 18 F-PSMA-1007, and 68 Ga-PSMA-11. Both 18 F-PSMA-1007 and 18 F-DCFPyL showed higher DRs than 68 Ga-PSMA-11 in primary and recurrent PC. PSMA tracers outperform non-PSMA alternatives for detecting biochemical recurrence. Among PSMA tracers, 18 F-labeled agents consistently surpass 68 Ga-PSMA-11 in both biochemically recurrent and primary PC. When available, 18 F-labeled PSMA tracers should be preferred.

Based upon recent phase3 trials, guidelines recommend early aggressive treatment for patients with high-risk biochemically recurrent nonmetastatic castration-sensitive prostate cancer. We assessed how this aligns with current real-world treatment patterns. Descriptive analyses were performed on data abstracted from an independent, retrospective, cross-sectional survey, which collected information regarding treatment from urologists and radiation oncologists in the United States between April and November 2023 who were managing patients with high-risk biochemically recurrent nonmetastatic castration-sensitive prostate cancer. Data were derived from physician responses to questions regarding their perspectives on treatment and patient record forms for their last 6-10 patients with high-risk biochemical recurrence. Although the survey was retrospective in nature and not based on a true random sample of physicians and patients, the relatively minimal inclusion criteria used attempted to ensure a broad representation of physicians and patients with high-risk biochemically recurrent prostate cancer. An analysis cohort of 87 physicians submitted data for 535 eligible patients. Median time from diagnosis with high-risk biochemical recurrence to first-line treatment was 20days. Median time between high-risk biochemical recurrence diagnosis and end of data collection was 286days. The most common first-line treatments were androgen deprivation therapy alone (28%), radiation (20%), androgen receptor pathway inhibitor + androgen deprivation therapy (19%), and observation (13%). Among patients who received androgen deprivation therapy, 79% received it continuously. Adherence to treatment guidelines (cited by 49%) was the most common reason for physicians' first-line treatment choice. In our real-world analysis, patients with high-risk biochemically recurrent prostate cancer rapidly received first-line treatment after diagnosis. The top reason for treatment choice was adherence to guidelines. Our finding that patients with biochemical recurrence are promptly treated in the real world aligns with guidance suggesting clinical benefit of early intervention.

The current EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines recommend radiolabeled prostate-specific membrane antigen (PSMA), choline, or fluciclovine PET/CT at biochemical recurrence (BCR) of prostate cancer (PCa) after radical prostatectomy. While studies compared [68Ga]Ga-PSMA-11 and [18F]Fluciclovine, data on 18F-labelled PSMA-ligands versus [18F]Fluciclovine in patients with low prostate-specific antigen (PSA) levels (< 2 ng/mL) are limited. This study compared the detection rates of [18F]Fluciclovine and [18F]DCFPyL PET/CT in patients with BCR after robot-assisted radical prostatectomy (RARP). Secondary objectives included stratifying detection rates by PSA level, anatomical regions and assessing inter-observer agreement. In this prospective, single-center study, patients with BCR (PSA 0.2-2.0 ng/mL) underwent both [18F]Fluciclovine and [18F]DCFPyL PET/CT within 15 days. Three blinded nuclear medicine experts independently reviewed all scans. Lesions were classified as positive or negative in predefined regions (i.e., prostate bed, pelvic and extra-pelvic lymph nodes, bone, and visceral). Discrepancies were resolved by consensus, defined as majority agreement (≥ 2/3 readers). Inter-observer agreement was assessed using Fleiss’ kappa. Overall scan positivity was 44% (22/50 patients) for [18F]DCFPyL PET/CT and 24% (12/50) for [18F]Fluciclovine PET/CT (p = 0.018). Detection rates increased with rising PSA levels for both tracers. Local recurrence was detected by both tracers in 16% (8/50) of patients. Metastatic disease detection rates for [18F]DCFPyL versus [18F]Fluciclovine were 22% vs. 8.0% for pelvic lymph nodes (p = 0.016), and 6.0% versus 2.0% for distant metastases (p = 0.50), respectively. Inter-observer agreement was moderate for both tracers (κ = 0.59 for [18F]DCFPyL and κ = 0.55 for [18F]Fluciclovine). This study demonstrated the superiority of [18F]DCFPyL over [18F]Fluciclovine in detecting pelvic lymph node metastases in patients presenting with BCR after RARP at low PSA levels. These findings suggest the potential of [18F]DCFPyL PET/CT to facilitate earlier and more personalized salvage treatment strategies.

Approximately 20-50% of patients develop biochemical recurrence (BCR) of prostate cancer within 10 years following radical prostatectomy (RP). The accurate identification of recurrent disease is crucial for guiding salvage treatment decisions. While multiparametric MRI (mpMRI) and prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) are both utilized for detecting local recurrence, their combined diagnostic benefits remain unclear. This study seeks to evaluate the diagnostic performance of both modalities alone and in conjunction for detecting local recurrence following RP in patients with BCR. A retrospective single-institution analysis included 37 post-RP patients with BCR who received mpMRI and PSMA PET/CT. Five board-certified radiologists reviewed images in three phases: mpMRI only, PSMA PET/CT only, and both modalities combined. Multidisciplinary tumor board consensus served as the reference standard. Diagnostic performance, inter-reader agreement, and radiologist confidence with each modality was examined. MpMRI outperformed PSMA PET/CT, yielding a higher sensitivity (73.0% vs. 65.2%) and specificity (77.1% vs. 75.7%). Interpretation of mpMRI and PSMA PET/CT together achieved the highest diagnostic accuracy (77.8%), representing a statistically-significant increase over PSMA PET/CT (p = 0.026) but a non-statistically-significant increase over mpMRI (p = 0.441). Combined imaging also resulted in greater specificity (90.0%) and inter-rater reliability (κ = 0.622). However, in some cases performance decreased with both modalities due to interpretive pitfalls. While mpMRI remains the preferred imaging modality for post-RP local recurrence surveillance, the integration of PSMA PET/CT may lead to improved specificity and inter-rater reliability. However, radiologists must understand each modality's limitations to avoid interpretive pitfalls.

Focal Cryo-Ablation for Treatment of Intermediate Favorable Risk (Grade Group 2) Prostate Cancer.

Re: Improved Survival with Enzalutamide in Biochemically Recurrent Prostate Cancer.

Positive surgical margins (PSMs) after robot-assisted radical prostatectomy (RARP) increase the risk of prostate cancer recurrence, often requiring salvage treatments that may compromise functional recovery. Intraoperative frozen section can detect PSM but is not feasible as a routine approach in most settings. Ex vivo fluorescence confocal microscopy (FCM) provides a rapid, real-time alternative, though evidence remains limited and knowledge gaps persist. This international Delphi consensus aimed to define expert recommendations on the clinical application of and workflow and research priorities for the safe integration of FCM during RARP. A modified Delphi process was conducted following the RAND/UCLA Appropriateness Method and reported according to the ACCORD checklist. In total, 32 international experts in urology and pathology participated in a hybrid consensus meeting after structured literature review and preparatory online sessions. Forty-four evidence-based multiple-choice items across patient selection, image acquisition, and surgical management domains were developed and anonymously voted on via a secure online platform. Consensus was predefined as ≥80% agreement among respondents. Consensus was achieved for 24 of 44 items (55%). Key agreements included a risk-adapted use of FCM (97%), its role as an adjunct to magnetic resonance imaging for nerve-sparing decisions (87%), adoption of en-face imaging as the preferred FCM technique (82%), and a maximum reporting time of 30 min (85%). The panel endorsed formal certification for image interpretation (83%), standardized reporting of positive margin length (82%), and feasibility of remote intra-institutional reporting (84%). Larger (>3 mm) PSM in high-risk cases warranted complete neurovascular bundle resection (96%). This consensus provides a structured framework for the intraoperative use of FCM during RARP, defining its indications, workflow standards, and training requirements. Future multicentre studies are needed to assess its oncological and functional impact and to establish standardized implementation pathways.

Aglatimagene besadenovec (CAN-2409) with radiotherapy for patients with localised prostate cancer: a phase 3, multicentre, randomised, double-blind, placebo-controlled trial.

Efficacy and safety of salvage brachytherapy for local recurrence after radiotherapy for prostate cancer.