PSMA PET/CT: joint EANM procedure guideline/SNMMI procedure standard for prostate cancer imaging 2.0.

Here we aim to provide updated guidance and standards for the indication, acquisition, and interpretation of PSMA PET/CT for prostate cancer imaging. Procedures and characteristics are reported for a variety of available PSMA small radioligands. Different scenarios for the clinical use of PSMA-ligand PET/CT are discussed. This document provides clinicians and technicians with the best available evidence, to support the implementation of PSMA PET/CT imaging in research and routine practice.

Joint EANM/SNMMI procedure guideline for the use of 177Lu-labeled PSMA-targeted radioligand-therapy (177Lu-PSMA-RLT).

Prostate-specific membrane antigen (PSMA) is expressed by the majority of clinically significant prostate adenocarcinomas, and patients with target-positive disease can easily be identified by PSMA PET imaging. Promising results with PSMA-targeted radiopharmaceutical therapy have already been obtained in early-phase studies using various combinations of targeting molecules and radiolabels. Definitive evidence of the safety and efficacy of [177Lu]Lu-PSMA-617 in combination with standard-of-care has been demonstrated in patients with metastatic castration-resistant prostate cancer, whose disease had progressed after or during at least one taxane regimen and at least one novel androgen-axis drug. Preliminary data suggest that 177Lu-PSMA-radioligand therapy (RLT) also has high potential in additional clinical situations. Hence, the radiopharmaceuticals [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T are currently being evaluated in ongoing phase 3 trials. The purpose of this guideline is to assist nuclear medicine personnel, to select patients with highest potential to benefit from 177Lu-PSMA-RLT, to perform the procedure in accordance with current best practice, and to prepare for possible side effects and their clinical management. We also provide expert advice, to identify those clinical situations which may justify the off-label use of [177Lu]Lu-PSMA-617 or other emerging ligands on an individual patient basis.

The Emerging Role of Next-Generation Imaging in Prostate Cancer.

PURPOSE OF REVIEW: Prostate cancer (PCa) is the most frequently diagnosed malignancy in men in developed countries and a leading cause of cancer death worldwide. Effective methods for diagnosing and staging PCa are necessary to guide treatment options in a personalized manner. The purpose of this paper is to review recent advances in molecular imaging and therapeutics and their expanding role in imaging and treating PCa. RECENT FINDINGS: Compared with conventional imaging, PSMA PET has proven more accurate at detecting PCa in patients with newly diagnosed PCa or biochemically recurrent PCa. PSMA PET can also induce management changes in patients due to its superior accuracy in detecting metastatic disease. Further research is necessary to understand the appropriate role of PSMA PET in patients with known metastatic PCa and the impact on clinical outcomes in patients who undergo treatment planning using findings from PSMA PET. We review the role of molecular imaging in primary and biochemically recurrent PCa. We find that molecular imaging is effective in detecting PCa and may lead to management changes.

First-in-human clinical trial to assess pharmacokinetics, pharmacodynamics, safety, and tolerability of iscalimab, an anti-CD40 monoclonal antibody.

Iscalimab is a fully human, CD40 pathway blocking, nondepleting monoclonal antibody being developed as an immunosuppressive agent. We describe a first-in-human, randomized, double-blind, placebo-controlled study investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of iscalimab in healthy subjects and rheumatoid arthritis patients. Healthy subjects (n = 56) received single doses of intravenous iscalimab (0.03, 0.1, 0.3, 1, or 3 mg/kg), or subcutaneous iscalimab (3 mg/kg), or placebo. Rheumatoid arthritis patients (n = 20) received single doses of intravenous iscalimab (10 or 30 mg/kg) or placebo. Iscalimab exhibited target-mediated drug disposition resulting in dose-dependent and nonlinear pharmacokinetics. Complete (≥90%) CD40 receptor occupancy on whole blood B cells was observed at plasma concentrations >0.3-0.4 µg/mL. In subjects receiving 3 mg/kg iscalimab, antibody responses to keyhole limpet hemocyanin were transiently suppressed. CD40 occupancy by iscalimab prevented ex vivo human rCD154-induced expression of CD69 on B cells in whole blood. All doses were generally safe and well tolerated, with no clinically relevant changes in any safety parameters, including no evidence of thromboembolic events. Iscalimab appears to be a promising blocker of the CD40-CD154 costimulatory pathway with potential use in transplantation and other autoimmune diseases.

Utility of Quantitative SPECT/CT Lymphoscintigraphy in Guiding Sentinel Lymph Node Biopsy in Head and Neck Melanoma.

PURPOSE: To investigate the use of advanced SPECT/CT quantification in guiding surgical selection of positive sentinel lymph nodes (SLNs) in head and neck melanoma. METHODS: We retrospectively reviewed data from patients with cutaneous head and neck melanoma who underwent lymphoscintigraphy with SPECT/CT prior to SLN biopsy (SLNB). Quantification of radiotracer uptake from SPECT/CT data was performed using in-house segmentation software. SLNs identified using SPECT/CT were compared to SLNs identified surgically using an intraoperative γ-probe. A radioactivity count threshold using SPECT/CT for detecting a positive SLN was calculated. RESULTS: One hundred and five patients were included. Median number of SLNs detected was 3/patient with SPECT/CT and 2/patient with intraoperative γ-probe. The hottest node identified by SPECT/CT and intraoperative γ-probe were identical in 85% of patients. All 20 histologically positive SLNs were identified by SPECT/CT and γ-probe. On follow-up, all nodal recurrences occurred at lymph node levels with the hottest node identified by SPECT/CT and either the hottest or second hottest node identified by γ-probe during SLNB. Using our data, a SPECT/CT radioactivity count threshold of 20% would eliminate the unnecessary removal of 11% of SPECT/CT identified nodes and 12% of intraoperatively detected nodes. CONCLUSION: Utilizing SPECT/CT quantification, we propose that a radioactivity count threshold can be developed to help guide the selective removal of lymph nodes in head and neck SLNB. Furthermore, the nodal level containing the hottest node identified by SPECT/CT quantification must be thoroughly investigated for SLNs and undergo careful follow-up and surveillance for recurrence.

Evolving understanding and categorization of prostate cancer: preventing progression to metastatic castration-resistant prostate cancer: RADAR IV.

INTRODUCTION To interpret data and update the traditional categorization of prostate cancer in order to help treating clinicians make more informed decisions. These updates include guidance regarding how to best use next generation imaging (NGI) with the caveat that the new imaging technologies are still a work in progress. MATERIALS AND METHODS: Literature review. RESULTS: Critical goals in prostate cancer management include preventing or delaying emergence of distant metastases and progression to castration-resistant disease. Pathways for progression to metastatic castration-resistant prostate cancer (mCRPC) involve transitional states: nonmetastatic castration-resistant prostate cancer (nmCRPC), metastatic hormone-sensitive prostate cancer (mHSPC), and oligometastatic disease. Determination of clinical state depends in part on available imaging modalities. Currently, fluciclovine and gallium-68 (68Ga) prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) are the NGI approaches with the most favorable combination of availability, specificity, and sensitivity. PET imaging can be used to help guide treatment selection in most patients. NGI can help determine patients who are candidates for new treatments, most notably (next-generation androgen antagonists, eg, apalutamide, enzalutamide, darolutamide), that can delay progression to advanced disease. CONCLUSIONS: It is important to achieve a consensus on new and more easily understood terminology to clearly and effectively describe prostate cancer and its progression to health care professionals and patients. It is also important that description of disease states make clear the need to initiate appropriate treatment. This may be particularly important for disease in transition to mCRPC.

A Clinician's Guide to Next Generation Imaging in Patients With Advanced Prostate Cancer (RADAR III).

PURPOSE: The advanced prostate cancer therapeutic landscape has changed dramatically in the last several years, resulting in improved overall survival of patients with castration naïve and castration resistant disease. The evolution and development of novel next generation imaging techniques will affect diagnostic and therapeutic decision making. Clinicians must navigate when and which next generation imaging techniques to use and how to adjust treatment strategies based on the results, often in the absence of correlative therapeutic data. Therefore, guidance is needed based on best available information and current clinical experience. MATERIALS AND METHODS: The RADAR (Radiographic Assessments for Detection of Advanced Recurrence) III Group convened to offer guidance on the use of next generation imaging to stage prostate cancer based on available data and clinical experience. The group also discussed the potential impact of next generation imaging on treatment options based on earlier detection of disease. RESULTS: The group unanimously agreed that progression to metastatic disease is a seminal event for patient treatment. Next generation imaging techniques are able to detect previously undetectable metastases, which could redefine the phases of prostate cancer progression. Thus, earlier systemic or locally directed treatment may positively alter patient outcomes. CONCLUSIONS: The RADAR III Group recommends next generation imaging techniques in select patients in whom disease progression is suspected based on laboratory (biomarker) values, comorbidities and symptoms. Currently 18F-fluciclovine and 68Ga prostate specific membrane antigen positron emission tomography/computerized tomography are the next generation imaging agents with a favorable combination of availability, specificity and sensitivity. There is ongoing research of additional next generation imaging technologies, which may offer improved diagnostic accuracy and therapeutic options. As next generation imaging techniques evolve and presumably result in improved global accessibility, clinician ability to detect micrometastases may be enhanced for decision making and patient outcomes.

Diagnostic Accuracy of F-18 FDG PET/CT for Preoperative Lymph Node Staging in Newly Diagnosed Bladder Cancer Patients: A Systematic Review and Meta-Analysis.

AIMS: We aimed to assess the diagnostic accuracy of F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for preoperative lymph node (LN) staging in newly diagnosed bladder cancer (BC) patients through a systematic review and meta-analysis. PATIENTS AND METHODS: MEDLINE, Embase, and the Cochrane Library database, from the earliest available date of indexing through June 30, 2017, were searched for studies evaluating the diagnostic performance of F-18 FDG PET/CT for preoperative LN staging in newly diagnosed BC. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR-), and constructed summary receiver operating characteristic curves. RESULTS: Across 14 studies (785 patients), the pooled sensitivity was 0.57 (95% CI: 0.49-0.64) and the pooled specificity was 0.92 (95% CI: 0.87-0.95). The LR syntheses gave an overall LR+ of 7.4 (95% CI: 4.4-12.3) and an LR- of 0.47 (95% CI: 0.39-0.56). The pooled diagnostic odds ratio was 16 (95% CI: 9-28). CONCLUSIONS: F-18 FDG PET/CT shows a low sensitivity and high specificity for the detection of metastatic LNs in patients with newly diagnosed BC.

Diagnostic accuracy of C-11 choline and C-11 acetate for lymph node staging in patients with bladder cancer: a systematic review and meta-analysis.

OBJECTIVE: We aimed to assess the diagnostic accuracy of C-11 choline and C-11 acetate positron emission tomography/computed tomography (PET/CT) for lymph node (LN) staging in bladder cancer (BC) patients through a systematic review and meta-analysis. METHODS: The MEDLINE, EMBASE, and Cochrane Library database, from the earliest available date of indexing through June 30, 2017, were searched for studies evaluating the diagnostic performance of C-11 choline and C-11 acetate PET/CT for LN staging in BC. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR-), and constructed summary receiver operating characteristic curves. RESULTS: Across 10 studies (282 patients), the pooled sensitivity was 0.66 (95% CI 0.54-0.75) without heterogeneity (χ2 = 12.4, p = 0.19) and a pooled specificity of 0.89 (95% CI 0.76-0.95) with heterogeneity (χ2 = 29.1, p = 0.00). Likelihood ratio (LR) syntheses gave an overall positive likelihood ratio (LR+) of 5.8 (95% CI 2.7-12.7) and negative likelihood ratio (LR-) of 0.39 (95% CI 0.28-0.53). The pooled diagnostic odds ratio (DOR) was 15 (95% CI 6-38). In meta-regression analysis, the study design (prospective vs retrospective) was the source of the study heterogeneity. CONCLUSION: C-11 choline and C-11 acetate PET/CT shows a low sensitivity and moderate specificity for the detection of metastatic LNs in patients with BC. Moreover, heterogeneity among the studies should be considered a limitation. Further large multicenter studies would be necessary to substantiate the diagnostic accuracy of C-11 choline and C-11 acetate PET/CT for this purpose.

Validation of Software Gating: A Practical Technology for Respiratory Motion Correction in PET.

Purpose To assess the performance of hardware- and software-gating technologies in terms of qualitative and quantitative characteristics of respiratory motion in positron emission tomography (PET) imaging. Materials and Methods Between 2010 and 2013, 219 fluorine 18 fluorodeoxyglucose PET examinations were performed in 116 patients for assessment of pulmonary nodules. All patients provided informed consent in this institutional review board-approved study. Acquisitions were reconstructed as respiratory-gated images by using hardware-derived respiratory triggers and software-derived signal (via an automated postprocessing method). Asymmetry was evaluated in the joint distribution of reader preference, and linear mixed models were used to evaluate differences in outcomes according to gating type. Results In blind reviews of reconstructed gated images, software was selected as superior 16.9% of the time (111 of 657 image sets; 95% confidence interval [CI]: 14.0%, 19.8%), and hardware was selected as superior 6.2% of the time (41 of 657 image sets; 95% CI: 4.4%, 8.1%). Of the image sets, 76.9% (505 of 657; 95% CI: 73.6%, 80.1%) were judged as having indistinguishable motion quality. Quantitative analysis demonstrated that the two gating strategies exhibited similar performance, and the performance of both was significantly different from that of nongated images. The mean increase ± standard deviation in lesion maximum standardized uptake value was 42.2% ± 38.9 between nongated and software-gated images, and lesion full width at half maximum values decreased by 9.9% ± 9.6. Conclusion Compared with vendor-supplied respiratory-gating hardware methods, software gating performed favorably, both qualitatively and quantitatively. Fully automated gating is a feasible approach to motion correction of PET images. (©) RSNA, 2016 Online supplemental material is available for this article.

SPECT/CT Improves Detection of Metastatic Sentinel Lymph Nodes in Patients with Head and Neck Melanoma.

BACKGROUND: A positive sentinel lymph node (SLN) is the most important prognostic factor for predicting survival in cutaneous melanoma. This study aimed to evaluate how the addition of single-photon emission computed tomography (SPECT) and computed tomography (CT) to planar lymphoscintigraphy (PL) alters SLN identification, yield, and localization of metastatic nodes in head and neck melanoma. METHODS: This retrospective review examined patients undergoing SLN biopsy for cutaneous melanoma of the head and neck between July 2003 and December 2015. Patient demographics and pathologic outcomes were compared for patients undergoing SPECT-CT versus PL. A multivariable logistic regression analysis was used to identify factors associated with the identification of a positive SLN. RESULTS: Among 176 patients undergoing SLN biopsy, 91 underwent PL and 85 underwent SPECT-CT and PL. The patients in the SPECT-CT group were older than the PL patients (p = 0.050) but the groups did not differ in gender (p = 0.447), Breslow thickness (p = 0.744), or total number of SLNs identified (p = 0.633). As shown by the multivariate regression analysis, only Breslow thickness [odds ratio (OR) 1.47; 95 % confidence interval (CI) 1.17-1.84] and SPECT-CT (OR 3.58; 95 % CI 1.24-10.4) were associated with a positive SLN. CONCLUSION: The use of SPECT-CT for patients with head and neck cutaneous melanoma significantly increases the likelihood of retrieving a positive SLN. Long-term follow-up evaluation is needed for further definition of the impact that SPECT-CT has on recurrence and survival.

Changes in Total Lesion Glycolysis Evaluated by Repeated F-18 FDG PET/CT as Prognostic Factor in Locally Advanced Esophageal Cancer Patients Treated with Preoperative Chemoradiotherapy.

AIMS: The present study was aimed to investigate whether volumetric parameters measured by sequential F-18 fluoro-D-glucose (F-18 FDG) positron emission tomography/computed tomography (PET/CT) could be used as prognostic factors in patients with locally advanced esophageal cancer (LAEC) who received preoperative chemoradiotherapy (CRT). METHODS: A total of 61 patients with LAEC were included in the current study. All patients were evaluated by F-18 FDG PET/CT before and after 46 Gy of radiotherapy with a concurrent cisplatin-based chemotherapy. Initial, second, and percent changes (Δ, %) of semiquantitative and volumetric parameters were used to calculate recurrence-free survival (RFS) and overall survival (OS). The median values of each parameter were used as cutoff values. The prognostic significance was assessed using univariate and multivariate Cox proportional hazard regression analyses. RESULTS: Cox proportional hazard regression analyses revealed that change in total lesion glycolysis (ΔTLG) was a potent predictor of RFS and OS. Kaplan-Meier survival curves showed better prognosis in higher ΔTLG. CONCLUSION: Our data suggest that ΔTLG measured by sequential F-18 FDG PET/CT after preoperative CRT could provide prognostic information in LAEC patients.

Cognitive-Motor Related Brain Activity During Walking: Differences Between Men and Women With Multiple Sclerosis.

OBJECTIVE: To determine if sex differences in glucose uptake, a marker of brain activity, are present in brain regions that facilitate walking performance in persons with multiple sclerosis (MS). DESIGN: Cross-sectional, observational pilot. SETTING: University laboratory. PARTICIPANTS: Positron emission tomography with fluorine-18-labeled deoxyglucose (FDG) was performed on persons with MS and healthy controls (4 men and 4 women per group; N=16) after a 15-minute walking test. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Brain activity was quantified as the mean standardized uptake value (SUV). RESULTS: The mean SUV was significantly lower in the thalamus (P=.029) and cerebellum (P=.029) for men with MS compared with women with MS, but not for the prefrontal (P=.057) or frontal (P=.057) cortices. Similar nonsignificant trends were found for healthy controls. No mean SUV group × sex interaction effects were found between the MS and healthy control groups (all P>.05). CONCLUSIONS: To our knowledge, this is the first study of brain activity sex differences based on FDG uptake in persons with MS during walking. Significantly less FDG uptake in the thalamus and cerebellum brain regions important for walking performance was found in men with MS compared with women with MS; however, these comparisons were not significantly different in the healthy control group. No differences in FDG uptake were found between the MS and healthy control groups in any of the brain regions examined. Results from this study provide pilot data for larger studies aimed at identifying underlying mechanisms responsible for accelerated disability in men with MS.

The efficacy of (177)Lu-labelled peptide receptor radionuclide therapy in patients with neuroendocrine tumours: a meta-analysis.

PURPOSE: This study was performed to evaluate the efficacy of (177)Lu-labelled peptide receptor radionuclide therapy (PRRT) in patients with inoperable or metastatic neuroendocrine tumours (NETs). METHODS: Systematic searches of MEDLINE and EMBASE databases were performed using the keywords of "neuroendocrine", "(177)Lu" and "prognosis". All published studies of neuroendocrine tumours treated with (177)Lu-labelled radiopharmaceuticals and evaluated with either Response Evaluation Criteria in Solid Tumours (RECIST) 1.0 or Southwest Oncology Group (SWOG) criteria or both were included. If there was more than one published study from the same institution, only one report with the information most relevant to this study was included. Each response criteria group was analysed for disease response rates and disease control rates, defined as the percentages of patients with complete response (CR) + partial response (PR), and CR + PR + stable disease (SD), respectively, to a therapeutic intervention in clinical trials of anticancer agents. The pooled proportions are presented with both a fixed-effects model and random-effects model. RESULTS: Six studies with 473 patients (4 in RECIST criteria group with 356 patients, 3 in SWOG criteria group with 375 patients and 1 in both groups) were included. The RECIST criteria group demonstrated disease response rates ranging between 17.6 and 43.8% with a pooled effect of 29% [95% confidence interval (CI) 24-34%]. Disease control rates ranged from 71.8 to 100%. The random-effects model showed an average disease control rate of 81% (95% CI 71-91%). The SWOG criteria group demonstrated disease response rates ranging between 7.0 and 36.5% with a pooled effect of 23% (95% CI 11-38%). Disease control rates ranged from 73.9 to 89.1%. The random-effects model showed an average disease control rate of 82% (95% CI 71-91%). CONCLUSION: (177)Lu-labelled PRRT is an effective treatment option for patients with inoperable or metastatic NETs.

Cancer immunotherapy: imaging assessment of novel treatment response patterns and immune-related adverse events.

Cancer immunotherapy is changing the imaging evaluation of cancer treatment response and treatment-related toxic effects. New emerging patterns of treatment response and treatment-related toxic effects after treatment with immunomodulating agents have been observed. Treatment response after immunomodulatory therapy can be associated with significantly delayed decrease in tumor size, and new or enlarging tumors observed soon after completion of treatment may not reflect disease progression. In addition, activation of the immune system to fight cancer may lead to unwanted autoimmune-mediated toxic effects that could be mistaken for metastatic disease or misdiagnosed as a non-treatment-related process and delay appropriate clinical management. Radiologists must recognize the novel treatment response patterns and the wide range of autoimmune toxic effects, which should not be mistaken for treatment failure or metastatic disease progression.

Novel Imaging of Prostate Cancer with MRI, MRI/US, and PET.

Imaging of prostate cancer presents many challenges to the imaging community. There has been much progress in this space in large part due to MRI and PET radiopharmaceuticals. Though MRI has been focused on the evaluation of local disease and PET on the detection of metastatic disease, these two areas do converge and will be complementary especially with the growth of new PET/MRI technologies. In this review article, we review novel MRI, MRI/US, and PET radiopharmaceuticals which will offer insight into the future direction of imaging in prostate cancer.

Assessment of pharmacokinetic drug-drug interaction between pradigastat and acetaminophen in healthy subjects.

PURPOSE: The purpose of this study was to evaluate the effect of pradigastat, a diacylglycerol acyltransferase-1 inhibitor, on the pharmacokinetics of acetaminophen, a gastric emptying marker. METHODS: Twenty-five healthy subjects were enrolled and received 1000 mg acetaminophen with meal in period 1, pradigastat (100 mg × 3 days followed by 40 mg × 7 days, 1 h before meal) in period 2, and 1000 mg acetaminophen at -2, -1, 0, +1, and +3 h with respect to meal timing in presence of steady-state pradigastat (40-mg maintenance dose) during periods 3-7. RESULTS: The geometric mean ratio and 90% confidence interval of Cmax and AUC of acetaminophen were within 80-125% suggesting that the rate ad extent of acetaminophen were not affected when given at various time points with respect to pradigastat/meal timing. The acetaminophen Tmax was also not impacted under all treatment conditions but increased from 0.75 to 2.00 h when administered 1 h after food. CONCLUSION: In the presence of steady-state pradigastat, the pharmacokinetics of acetaminophen is unchanged, when given before, with, or 3 h after a meal. However, when given 1 h after a meal, the Tmax of acetaminophen was delayed by ∼1.25 h without affecting Cmax or AUC.

¹8F-NaF PET/CT and ¹¹C-Choline PET/CT for the initial detection of metastatic disease in prostate cancer: overview and potential utilization.

With the rapid increase in new therapies to treat advanced prostate cancer, improved diagnosis tools are necessary to help refine patient management throughout the entire disease course. Many radiopharmaceuticals, most of which are imaged using positron emission tomography/computed tomography (PET/CT), are in development; two of these newer radiopharmaceuticals are ¹8F-sodium fluoride (NaF) and radiolabeled choline. Compared with traditional imaging, use ¹8F-NaF has been shown to improve sensitivity and specificity, and radiolabeled choline has been shown to detect recurrent and metastatic disease earlier. We briefly review these two imaging technologies and provide potential utilization strategies based on available data.

Expert Perspectives on Controversies in Castration-Sensitive Prostate Cancer Management: Narrative Review and Report of the First US Prostate Cancer Conference Part 1.

Purpose: Castration-sensitive prostate cancer (CSPC) is a complex and heterogeneous condition encompassing a range of clinical presentations. As new approaches have expanded management options, clinicians are left with myriad questions and controversies regarding the optimal individualized management of CSPC. Materials and Methods: The US Prostate Cancer Conference (USPCC) multidisciplinary panel was assembled to address the challenges of prostate cancer management. The first annual USPCC meeting included experts in urology, medical oncology, radiation oncology, and nuclear medicine. USPCC co-chairs and session moderators identified key areas of controversy and uncertainty in prostate cancer management and organized the sessions with multidisciplinary presentations and discussion. Throughout the meeting, experts responded to questions prepared by chairs and moderators to identify areas of agreement and controversy. Results: The USPCC panel discussion and question responses for CSPC-related topics are presented. Key advances in CSPC management endorsed by USPCC experts included the development and clinical utilization of gene expression classifiers and artificial intelligence (AI) models for risk stratification and treatment selection in specific patient populations, the use of advanced imaging modalities in patients with clinically localized unfavorable intermediate or high-risk disease and those with biochemical recurrence, recommendations of doublet or triplet therapy for metastatic CSPC (mCSPC), and consideration of prostate and/or metastasis-directed radiation therapy in select patients with mCSPC. Conclusions: CSPC is a diverse disease with many therapeutic options and the potential for adverse outcomes associated with either undertreatment or overtreatment. Future studies are needed to validate and clinically integrate novel technologies, including genomics, AI, and advanced imaging, to optimize outcomes among patients with CSPC.