Historically, prostate cancer has been staged with conventional imaging (bone scan plus either CT or MRI). Since many of the studies supporting therapeutic interventions for prostate cancer are predicated on the results of conventional imaging (bone scan plus either CT or MRI), there remains some uncertainty regarding the potential for improved outcomes based on PSMA PET imaging modalities. Nonetheless, there is ample evidence of the greater sensitivity of PSMA PET as compared with conventional imaging for identification of nodal and distant disease, and evidence that findings of PSMA PET imaging can substantially alter the treatment plan and expectations regarding outcomes of treatment (e.g., finding small volume metastatic disease on PSMA PET in a patient otherwise thought to have localized disease by conventional imaging).91  PET imaging using F-18 piflufolastat or Gallium-68 PSMA-11 has been approved by the FDA for staging prostate cancer, and additional agents are approved for detection of recurrence and metastatic disease. PSMA PET imaging with these tracers is performed in conjunction with CT or MRI for localization. PSMA PET imaging is standard of care for staging in the setting of recurrence after primary treatment as well as in certain scenarios of advanced disease.92 In localized disease, the data regarding sensitivity of PSMA PET for nodal staging vary widely depending on the study. For example, a single-arm study of 764 men with unfavorable intermediate- and high-risk disease using gallium-68 PSMA-11 PET CT showed a relatively low sensitivity for lymph node involvement (40%) with a specificity of 95%.93 Meanwhile, the proPSMA trial, which enrolled 302 men with similar disease characteristics, showed far higher sensitivity for lymph node involvement using gallium-68 PSMA-11 PET CT (91%).91 By contrast, in detection of nodal metastasis, MRI has been found to be associated with a low to moderate sensitivity (range 0.09 to 0.44) and high specificity (range 0.88 to 1.0).65, 69, 70, 94, 95 Therefore, most studies in which PSMA PET has been compared with conventional imaging for nodal staging have shown greater sensitivity and overall accuracy for PSMA PET. In the proPSMA trial, sensitivity for pelvic lymph nodes was 59% for conventional imaging, a 32% absolute difference compared to 91% for gallium-68 PSMA-11 PET CT; PSMA PET also had an advantage in sensitivity for detection of metastatic disease (74% versus 95%).93 A meta-analysis including 31 studies (2,431 patients) of patients with intermediate- and high-risk disease, showed PSMA PET to be more sensitive and specific than mpMRI (73.7% versus 38.9% and 97.5% versus 82.6%) and CT (73.2% versus 38.5% and 97.8% versus 83.6%) for detection of nodal involvement.96 Additionally, PSMA PET was more sensitive and specific than bone scan for skeletal metastases (98.0% versus 73.0% and 96.2% versus 79.1%, respectively). Because of the incremental predictive value of PSMA PET, it has been incorporated into nomograms designed to predict lymph node metastases.97  Importantly, however, the studies showing low sensitivity of PSMA PET imaging for nodal metastases (e.g., the Hope study, which showed only 40% sensitivity) indicate that a negative PSMA PET scan does not rule out nodal involvement.93 Taken together, the Panel recommends staging imaging for patients with unfavorable intermediate- and high-risk prostate cancer. PSMA PET imaging, where available, provides improved sensitivity for identification of lymph node involvement and metastatic disease and, therefore, may be preferred. However, many of the treatment paradigms are predicated on conventional imaging, and the association between staging with PSMA PET imaging and downstream oncologic outcomes has not been established. While some studies of PSMA PET for initial staging have included all intermediate-risk patients,98 the evidence is strongest for the high-risk and unfavorable intermediate-risk patients. Therefore, the Panel determined that the data were insufficient to warrant recommending routine use of staging imaging in favorable intermediate-risk patients.