The use of PSA as an instrument of evaluation in metastatic prostate cancers is common practice. In most reported studies, PSA is a measured variable and recorded at several time points at diagnosis and during treatment (baseline, induction [after a defined period of therapy], serial monitoring, and at progression). In many studies, PSA has demonstrated clear prognostic value and is used in many of the risk classification systems. In the SWOG 8894 trial, a comparison of bilateral orchiectomy with or without flutamide for treatment of metastatic prostate cancer, many clinical factors were analyzed in the assessment of risk including the finding that a higher PSA (adjusted OR=1.18 for log PSA; 95% CI: 1.03 to 1.34) was associated with poorer 10-year survival.77 Studies using the SEER registry database have found higher PSA is associated with worse cancer-specific survival (PSA <60 versus ≥60: HR=0.624; 95% CI: 0.535 to 0.727).78 Additionally, for studies showing prognostic risk group stratification, PSA or PSA metrics are consistent variables in determination of group assignment.79-81    PSA decline after initiation of ADT (nadir) has been shown to be prognostic based on several studies and is useful in patient counseling. It is also likely useful in risk stratification for clinical trials. There are several prospective studies that have demonstrated the power of the PSA nadir in risk stratification. In an early analysis of SWOG 9346 looking at intermittent ADT in patients with metastatic prostate cancer, results demonstrated that PSA nadir at 7 months, ≤4ng/mL versus >4ng/mL, risk stratified patients receiving ADT, showing median survivals of 69 months versus 16 months, p<0.0001.82 This was followed by a later analysis of SWOG 9346 trial demonstrating that PSA nadir after six to seven months of ADT in newly diagnosed metastatic prostate cancer patients was prognostic for survival. An initial analysis demonstrated 3 prognostic groups could be identified based on PSA nadir; PSA >4, PSA 0.2 to 4, and PSA <0.2 with median survivals of 13 months, 44 months, and 75 months, respectively (p<0.001).83 Obtaining PSA at three- to six-month intervals allows for determination of the nadir and risk group stratification, and assists in patient counseling and setting expectations. With the changes in systemic therapy combinations, it is important to validate the prognostic value of nadir in more contemporary systemic settings. A recent analysis of the CHAARTED study showed PSA nadir at 7 months was a strong prognostic factor for OS when comparing nadirs ≤0.2ng/mL versus >4ng/mL (60.4 months versus 22.2 months, P<.001).84 Similar analyses are being explored from RCTs previously evaluating abiraterone acetate as well as second generation AR targeted therapies to determine if the prognostic value will hold true with more potent androgen axis therapies. PSA has also been used for determination of treatment changes or alterations based on the belief that it provides insight as a measure of adequate response and in defining progression to castration resistance. There is no general consensus, but consideration for the use of PSA for defining an adequate response include length of initial treatment if induction of intermittent ADT is being considered as well as timing of re-initiation of therapy. PSA is also used in identifying CRPC, which includes a definition of rising PSA in the setting of a castrate level of testosterone. Definitions of CRPC are variable, but a common one is from the Prostate Cancer Working Group, which is now on the third version of a consensus on CRPC progression. This includes measuring PSA and identifying rising values at a minimum of 1-week intervals with a minimal value of 2.0ng/mL, with estimations of PSADT with at least 3 values measured ≥4 weeks apart.85 Use of periodic testosterone measurement may also be used to confirm response to ADT. There is clearly a consistent use of PSA and PSA metrics in the evaluation and risk stratification for men with HSPC; therefore, the recommendation for obtaining baseline levels and values every three to six months for monitoring is practical. Clinicians should be aware, however, that PSA alone is not completely predictive of cancer progression as some patients may demonstrate cancer growth in the absence of a PSA rise. This is particularly true in poorly differentiated, ductal, and neuroendocrine tumors as well as mCRPC. Symptom assessment is an important adjunct in these cases. Given that metastatic disease can progress in these patients even with relatively stable PSAs, periodic imaging is reasonable to assess disease stability. There is no set interval for imaging of men with mHSPC, but imaging can demonstrate progression in the absence of PSA changes or in the absence of symptoms and should be considered as a method of evaluation of these patients. Imaging can include PSMA PET or conventional imaging (CT, MRI, bone scan).