Editing Prostate Cancer: Diagnosis and evaluation (section)

====== Potential roles of PSMA-PET imaging in prostate cancer ======

# '''<span style="color:#ff0000">Primary staging of high-risk prostate cancer</span>'''
#* '''<span style="color:#ff00ff">proPSMA (2020)</span>'''
#**Objective: determine whether PSMA PET-CT prior to treatment in patient with high risk prostate cancer increases detection of metastases, compared to conventional imaging
#**'''Population: 300 males with high-risk (PSA ≥20, grade group ≥3, or ≥cT3) prostate cancer being considered for radical prostatectomy or radiotherapy'''
#**'''Randomized to Ga-PSMA-11 PET-CT vs. conventional imaging (CT and bone scan), followed by second-line cross-over imaging.'''
#***Second-line cross-over imaging was done within 14 days of baseline imaging, unless ≥3 distant metastases identified on first-line imaging.
#***At 6 months, patients underwent repeat imaging as per randomised group with cross-over if
#****Baseline imaging evidence of metastasis (N1 or M1)
#****Biochemical or clinical suspicion of residual or recurrent disease.
#***'''Primary outcome: accuracy (based on area under the curve (AUC)) of first-line imaging at identifying either pelvic nodal or distant metastatic disease, compared to assessment of metastases at 6 months (reference standard)'''
#****Metastatic disease disease was defined by hard and soft criteria based on histopathologic, imaging, clinical, and biochemical findings.
#***'''Results:'''
#****'''Primary outcome: accuracy (based on AUC) significantly improved with PSMA PET-CT compared to conventional imaging (absolute difference: 27%, 92% PSMA PET-CT vs. 65% conventional imaging)'''
#*****Sensitivity: 85% PSMA PET-CT vs. 38% conventional imaging
#*****Specificity: 98% PSMA PET-CT vs. 91% conventional imaging
#***** PSMA PET-CT more sensitive and specific than conventional imaging for both pelvic nodal or distant metastases
#**** '''Secondary outcomes:'''
#***** '''Change in management more common with PSMA PET-CT (28% PSMA PET-CT vs. 15% conventional imaging)'''
#***** Less equivocal findings with PSMA PET-CT
#***** Radiation exposure reduced with PSMA PET-CT (8 mSv PSMA PET-CT vs. 19 mSv conventional imaging)
#*** Limitations:
#****Lack of histopathological evidence of metastasis in majority of cases; unclear validity of reference standard used in this study
#*****Only 23% of positive cases (pelvic nodal or distant metastasis) met "hard" criteria to define metastasis (true positive).
#******Hard criteria were histopathology showing prostate adenocarcinoma, or change of a bone lesion to sclerotic or blastic on follow-up imaging.
#*** [https://pubmed.ncbi.nlm.nih.gov/32209449/ Hofman, Michael S., et al.] "Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study." ''The Lancet'' 395.10231 (2020): 1208-1216.
#** '''Clinical implications (2):'''
#**# '''PSMA PET/CT may identify nodes outside of the routine surgical field, as well as additional sites of distant disease'''
#**# '''Sensitivity of PSMA PET/CT in detecting nodal disease not high enough to avoid treatment of lymph nodes''' in patients with risk of lymph node involvement
# '''<span style="color:#ff0000">Improved quantification of metastatic burden</span>'''
#* '''Oligometastatic disease may be identified, and such patients may be offered management in clinical trials or metastasis-directed surgery.'''
# '''<span style="color:#ff0000">Staging of biochemical recurrence</span>'''
#* '''Most common indication for PSMA-targeted PET'''
#* '''Management of biochemical recurrence depends on disease extent:''' local recurrence of local recurrence with regional nodal metastases vs. distant metastatic disease
# '''<span style="color:#ff0000">Determining patient suitability for PSMA-targeted radionuclide therapy</span>'''
#* '''Both 177Lu and 225Ac PSMA-targeted radioligand therapy are emerging as promising therapies for castration-resistant disease.'''
# '''<span style="color:#ff0000">Primary detection of tumor as an adjunct to multiparametric MRI</span>'''
#* Role of PSMA-targeted PET as an adjunct to mpMRI for primary detection of clinically significant prostate cancer is not well-established