Editing Management of Localized Prostate Cancer (section)

==== Evidence ====
* '''Disease-specific and all-cause survival have been high and compare favorably with longer-term outcomes after prostatectomy or various forms of radiotherapy in similar-risk men of low-risk tumors'''
**Observational studies demonstrate cumulative incidence of prostate cancer-specific mortality or metastasis of <1% at 10 years[https://pubmed.ncbi.nlm.nih.gov/31918957/][https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480884/]
*Use of AS for low-risk disease increasing over time, but remains suboptimal[https://pubmed.ncbi.nlm.nih.gov/36862409/]
'''<span style="color:#ff0000">Disease Reclassification on AS</span>'''
* '''Reclassification vs. progression'''
** '''The term progression while on AS should be replaced with disease reclassification, since most patients meeting surveillance criteria who are found to have high-grade or more extensive disease on surveillance biopsies are thought to have been misclassified initially, rather than experiencing true disease progression'''
*** One study found that 36% of men with Gleason score 5-6 on needle biopsy were found to have higher-grade disease at radical prostatectomy when tertiary grade was considered. Another study found that the 10-year actuarial rate of upgrading on annual surveillance biopsies in a large active surveillance experience was ≈30%. The similarity in the rate of upgrading at radical prostatectomy, and reclassification to high-grade disease on annual biopsies for men with low-grade cancer, strongly suggest that initial misclassification is the more common reason for re-classification on surveillance, and not “true” disease progression from low to high grade.
* '''<span style="color:#ff0000">≈25-50% of patients on AS develop evidence of disease reclassification within 5 years, depending on their individual risk factors:</span>'''
** '''<span style="color:#ff0000">Patient factors</span>'''
*** '''<span style="color:#ff0000">Race</span>'''
**** '''<span style="color:#ff0000">African-American males are at increased risk of progression on AS[https://pubmed.ncbi.nlm.nih.gov/34239046/]</span>'''
*** '''<span style="color:#ff0000">Germline mutations[https://pubmed.ncbi.nlm.nih.gov/30309687/]</span>'''
**** '''<span style="color:#ff0000">BRCA</span>'''
***** '''<span style="color:#ff0000">BRCA 2 associated with higher risk than BRCA 1</span>'''
****** '''<span style="color:#ff0000">BRCA 1 associated with 4x higher risk of prostate cancer</span>'''
****** '''<span style="color:#ff0000">BRCA 2 associated with 9x higher risk of prostate cancer</span>, higher Gleason scores, more advanced tumor stage, and shorter median survival'''
*** Body mass index[https://pubmed.ncbi.nlm.nih.gov/32852532/]
***Age[https://pubmed.ncbi.nlm.nih.gov/27469419/]
***'''Age, comorbid illness, and willingness to adhere to surveillance strategies must also be considered during patient selection'''
** '''<span style="color:#ff0000">Disease factors</span>'''
*** '''PSA density''' has been a consistent '''independent predictor of disease reclassification''' (both cancer volume on biopsy and grade) during surveillance.[https://pubmed.ncbi.nlm.nih.gov/34181465/][https://pubmed.ncbi.nlm.nih.gov/27469419/]
***Bilateral disease[https://pubmed.ncbi.nlm.nih.gov/34181465/]
***Percent of positive cores[https://pubmed.ncbi.nlm.nih.gov/32852532/][https://pubmed.ncbi.nlm.nih.gov/25819722/] (not percentage of core involvement) on most recent biopsy
***History of any negative biopsy after diagnosis[https://pubmed.ncbi.nlm.nih.gov/32852532/][https://pubmed.ncbi.nlm.nih.gov/25819722/]
***Total number of biopsies without grade reclassification[https://pubmed.ncbi.nlm.nih.gov/27469419/]
***Time since diagnosis[https://pubmed.ncbi.nlm.nih.gov/32852532/]
***'''PSA kinetics (velocity or doubling time)''' has been associated with adverse pathology in men on surveillance, but '''not consistently associated with disease reclassification'''
*** 2 gene expression (Oncotype DX and Polaris, see PSA and Other Markers Chapter Notes) assays are now commercially available for prostate cancer and are integrated with baseline clinical variables to provide more precise risk assessment for patients; however, to date it is unknown what role these tests will have in AS