Editing Prostate Cancer: Diagnosis and evaluation (section)

======<span style="color:#ff0000">Free-PSA (fPSA)</span>======
* '''<span style="color:#ff0000">%fPSA varies directly with age and volume, and indirectly with total PSA. Does not vary by race.</span>'''
*'''<span style="color:#ff0000">Low %fPSA is associated with increased risk of prostate cancer'''
**'''PSA produced by malignant cells escapes proteolytic processing more frequently, resulting in a <span style="color:#ff0000">greater fraction of serum PSA complexed</span> to α1-antichymotrypson and a lower %fPSA compared to men without cancer'''
**'''<span style="color:#ff00ff">Catalona et al. (1998)</span>'''
***Population:
****Prospective cohort study of 773 men aged 50-75 enrolled primarily through screening centers with PSA 4-10 and palpably benign gland that underwent diagnostic biopsy
*****49% had cancer, 51% had benign disease
*** Primary outcome:
****%fPSA that maintained 95% sensitivity for PC detection
***Results:
****%fPSA was inversely associated with risk of cancer
****AUC 0.72 %fPSA vs. 0.53 total PSA
****%fPSA cut-off:
*****≤25: sensitivity: 95%, specificity 20%
***** ≤22: sensitivity 90%, specificity 29%
****INSERT FIGURE
***Catalona, William J., et al. "Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter clinical trial." ''Jama'' 279.19 (1998): 1542-1547.
**'''%fPSA as a test is FDA-approved in men with a total PSA 4-10ng/mL and negative DRE'''
***'''%fPSA is most useful in the setting of PSA levels < 10ng/ml because the PPV of tPSA > 10- 20ng/ml has been shown to be ≈80%; it’s utility in PSA <4.0ng/ml is unknown'''
*** '''No %fPSA threshold has been established, proposed cut points generally range from 15-25%'''
***'''Debate remains surrounding the utility of %fPSA as a prognostic biomarker'''
*'''Complexed-PSA (as opposed to the free-PSA)'''
**'''Overall, at a high sensitivity, cPSA provides higher specificity than tPSA and comparable specificity to %fPSA in prostate cancer detection. A potential advantage of cPSA is the requirement for one assay''' 
*'''<span style="color:#ff0000">5ARIs lower total PSA levels by ≈50% after 12 months of treatment</span>'''
** '''With the use of 5ARIs, fPSA decreases in a similar fashion to tPSA, and the %fPSA is not altered significantly'''
**'''Finasteride 1 mg (Propecia) used for male pattern hair loss (androgenic alopecia) results in the same decline in serum PSA levels as the 5-mg dosage used for the treatment of BPH'''
**'''In the PCPT trial, PSA had statistically significantly better sensitivity and AUC for detecting prostate cancer in the finasteride arm[https://www.ncbi.nlm.nih.gov/pubmed/16912265]'''