Editing AUA: Advanced Prostate Cancer (2023) (section)

== Background ==

* Population covered in this guideline is assumed to have already received local or pelvic therapy, including adjuvant and salvage therapy (i.e., exhaustion of local treatment options).
* '''<span style="color:#ff0000">For the purpose of this guideline, consider ‘metastatic’ disease based on conventional imaging.</span>'''
** '''<span style="color:#ff0000">Definition of conventional imaging (3):</span>'''
**# '''<span style="color:#ff0000">CT</span>'''
**# '''<span style="color:#ff0000">MRI</span>'''
**# '''<span style="color:#ff0000">Bone scan (99mTc-methylene diphosphonate)</span>'''
** '''<span style="color:#ff0000">Conventional imaging infrequently detect metastases in the setting of early PSA recurrence (e.g., PSA <5 ng/mL).</span>'''
** '''<span style="color:#ff0000">Novel PET-CT scans have higher sensitivity than conventional imaging for the detection of prostate cancer recurrence and metastases at low PSA values (<2.0ng/mL).</span>'''
*** '''<span style="color:#ff0000">Oligometastatic disease may be identified, and such patients may be offered management in clinical trials or metastasis-directed surgery.</span>'''
**** '''<span style="color:#ff0000">Unknown if earlier identification of metastatic disease with the use of novel PET-CT scans improves overall survival.</span>'''
*** '''<span style="color:#ff0000">PET tracers (3):</span>'''
***# '''<span style="color:#ff0000">18F-fluciclovine</span>''' (pylarify)
***#* '''<span style="color:#ff0000">Most commonly used radiotracer in the U.S.</span>'''
***#* '''<span style="color:#ff0000">MOA: images amino acid metabolism.</span>'''
***#* Detection rate appears dependent upon both PSA kinetics and histologic grade.
***#* '''<span style="color:#ff0000">Outperforms standard CT in detection of nodal metastasis</span>'''
***#** Smallest short-axis diameter of nodes exhibiting uptake is 4-9mm, superior to CT.
***#* '''<span style="color:#ff0000">Comparable to standard bone scintigraphy in detection of bone metastases</span>'''
***#** Studies are limited.
***#* '''FDA approved for patients for whom local therapy fails to control disease.'''
***# '''<span style="color:#ff0000">68Ga-PSMA-11</span>'''
***#* '''<span style="color:#ff0000">MOA:</span>''' radiolabeled small molecule that '''<span style="color:#ff0000">binds to the prostate-specific membrane antigen (PSMA) receptor.</span>'''
***#** '''<span style="color:#ff0000">PSMA is a transmembrane protein highly overexpressed in >90% of prostate cancers.</span>'''
***#* '''<span style="color:#ff0000">High specificity and sensitivity</span>'''
***#** '''<span style="color:#ff0000">Outperforms standard CT and MRI in detection of nodal and osseous metastases.</span>'''
***#*** In a recent prospective study of men who had undergone prostatectomy and had a rising PSA still under 2.0ng/mL, PSMA-PET detected occult metastases 4.54x significantly more frequently than fluciclovine-PET[https://pubmed.ncbi.nlm.nih.gov/31375469/ §]
***#** At the time of guideline publication, had not received FDA approval in the U.S. '''Received FDA approval''' in December 2020.[https://www.fda.gov/news-events/press-announcements/fda-approves-first-psma-targeted-pet-imaging-drug-men-prostate-cancer §]
***# '''<span style="color:#ff0000">11C-choline</span>'''
***#* '''Lower sensitivity and specificity for metastatic disease'''
***#* '''FDA approved but no longer in routine use for prostate cancer.'''
*Discuss treatment options with advanced prostate cancer patients based on life expectancy, comorbidities, preferences, and tumor characteristics, ideally in a multidisciplinary setting.