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

== Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) ==

* '''<span style="color:#ff0000">Definition of HSPC: prostate cancer that has either not yet been treated with ADT or is still responsive to ADT</span>''' as manifested by the absence of clinical progression, radiographic progression, or a rising PSA of ≥2.0 ng/mL above nadir.
** Also be referred to as castrate-sensitive prostate cancer, endocrine-sensitive prostate cancer, and hormone-naïve prostate cancer.
* '''<span style="color:#ff0000">Categorize patients as de novo metastatic or having progression in stage after prior failed treatment.</span>'''
** '''De novo metastatic disease''' is present at the time of initial prostate cancer diagnosis rather than recurring after previous treatment of localized cancer
*** '''Associated with poorer prognosis than recurrent disease.''' 

=== <span style="color:#ff0000">Diagnosis and Evaluation</span> ===
*'''<span style="color:#ff0000">History and Physical Exam</span>'''
** '''<span style="color:#ff0000">Presence of symptoms from metastatic disease</span>'''
*** Symptoms in mHSPC have been shown to have prognostic value.
* '''<span style="color:#ff0000">Imaging</span>'''
** '''<span style="color:#ff0000">Assess the extent of metastatic disease (lymph node, bone, and visceral metastasis) in newly diagnosed mHSPC</span>'''
*** Extent of metastatic disease influences response.
*** '''<span style="color:#ff0000">CHAARTED definition of high-volume vs. low-volume</span>'''
**** '''<span style="color:#ff0000">High-volume:</span>'''
***** '''<span style="color:#ff0000">Visceral metastasis or</span>'''
***** '''<span style="color:#ff0000">≥4 bone metastases with ≥ 1 beyond the vertebral bodies and pelvis</span>'''
**** '''<span style="color:#ff0000">Low-volume: all others</span>'''
*** '''<span style="color:#ff0000">LATITUDE definition of high-risk vs. low-risk</span>'''
**** '''<span style="color:#ff0000">High-risk: ≥2 of the following 3 criteria:</span>'''
****# '''<span style="color:#ff0000">Visceral metastases</span>'''
****# '''<span style="color:#ff0000">≥ 3 bony metastases</span>'''
****# '''<span style="color:#ff0000">Gleason score ≥ 8</span>'''
**** LATITUDE excluded patients with “Low-risk” disease
* '''<span style="color:#ff0000">Genetic testing</span>'''
**'''<span style="color:#ff0000">Offer germline testing</span>'''
**'''<span style="color:#ff0000">Consider somatic testing and genetic counseling</span>'''

=== <span style="color:#ff0000">Management</span> ===
* '''<span style="color:#ff0000">First-line: ADT in combination with either (4):</span>'''
*# '''<span style="color:#ff0000">Abiraterone acetate plus prednisone</span>'''
*# '''<span style="color:#ff0000">Enzalutamide</span>'''
*#'''<span style="color:#ff0000">Apalutamide</span>'''
*# '''<span style="color:#ff0000">Docetaxel</span>'''
*#* No comparative data on efficacy exist between these 4 options.
*#* '''See [[Metastatic Hormone-Sensitive Prostate Cancer|Metastatic Hormone-Sensitive Prostate Cancer Chapter Notes]] for details on trials'''
* '''<span style="color:#ff0000">Primary radiotherapy to the prostate</span>'''
** '''<span style="color:#ff0000">May be offered in selected mHSPC patients with low-volume (CHAARTED definition) metastatic disease.</span>'''
** '''See [[Metastatic Hormone-Sensitive Prostate Cancer|Metastatic Hormone-Sensitive Prostate Cancer Chapter Notes]]  for details on trials'''
* '''De Novo mHSPC'''
** '''In selected patients with de novo mHSPC, clinicians should offer ADT in combination with docetaxel and either abiraterone acetate plus prednisone or darolutamide.''' 
*'''ADT'''
** Castrate levels of testosterone (<50ng/dL) may be achieved with:
*** LHRH agonists
*** GnRH antagonists
*** Surgical castration
** '''GnRH antagonists and orchiectomy as monotherapy have a rapid onset of action and avoid the ‘testosterone flare’ seen with LHRH analogues alone making them useful in situations needing rapid hormone ablation such as impending spinal cord compression.'''
** '''First generation antiandrogens (bicalutamide, flutamide, nilutamide) should not be used in combination with LHRH agonists in patients with mHSPC, except to block testosterone flare.'''
*** '''In the first week after LHRH agonists are administered, there is typically a surge in LH resulting in an increase in circulating testosterone. This may cause clinical “flares,” which may be associated with worsening of disease symptoms (e.g., bone pain, urinary tract obstruction) in approximately 10% of patients. This surge can be “blocked” by short term (i.e., 4 weeks or less) of a first-generation antiandrogen'''
** '''Insufficient evidence to support the use of first generation antiandrogens as monotherapy.'''
* '''Oral androgen pathway directed therapy'''
** Includes abiraterone acetate plus prednisone, apalutamide, bicalutamide, darolutomide, enzalutamide, flutamide, nilutamide)
** '''Should not be offered without ADT'''
*** All of the data suggesting that additional therapy (chemotherapy or androgen receptor-targeted therapy [ART]) significantly improves OS was in the context of continuous ADT; the Panel generally advises against intermittent ADT in otherwise healthy patients with mHSPC.

* '''Follow-up'''
** '''Obtain a baseline PSA and serial PSAs at 3-6 month intervals after initiation of ADT and consider periodic conventional imaging.'''
*** PSA at 3-6 month intervals allows for determination of the nadir and risk group stratification
**** '''PSA nadir after 6 months of ADT in newly diagnosed metastatic prostate cancer patients has been shown to be prognostic for survival.'''
*** PSA is also used in identifying CRPC
*** '''PSA alone is not completely predictive of cancer progression as some patients may demonstrate cancer growth in the absence of a PSA rise''' (e.g. poorly differentiated, ductal, and neuroendocrine tumors as well as mCRPC).
**** '''Symptom assessment is an important'''
**** '''Periodic imaging is reasonable to assess disease stability.'''
***** No set interval for imaging of men with mHSPC.
** '''Periodic testosterone measurement may also be used to confirm response to ADT.'''