<p>Patients who are diagnosed with metastatic hormone-sensitive prostate cancer (mHSPC) may have significantly varied prognoses based on their underlying tumor biology and disease characteristics. Baseline and regular follow-up testing are important to monitor for changes in tumor characteristics that may signal improvement, disease recurrence, or the development of hormone-resistant disease.</p>

At baseline, I want to have imaging, prostate-specific antigen (PSA) measurements, and a comprehensive pathology assessment, including grading, done. I would also like to have a baseline serum testosterone level for 2 reasons. One is because it provides some expectation about the efficacy of ADT for the occasional patient who starts with a very low serum testosterone level, in whom ADT may be less effective. Also, it is helpful to know the baseline testosterone level in patients who might be candidates for future treatment interruptions so that we know if their testosterone has returned to normal if treatment is interrupted later.

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We also routinely recommend and offer tumor and germline genetic testing, particularly to those with de novo mHSPC. The results of the genetic testing probably have a greater impact on treatment considerations in patients who progress to castration-resistant disease, but certain results may also influence decisions about the optimal systemic therapy for those with mHSPC. Other information gathered from genetic testing may help clarify the patient’s risk for disease progression. For example, having de novo metastatic disease with genetic mutations in multiple tumor suppressor genes may be predictive of a worse outcome and therefore supports the decision to intensify therapy with ADT plus an ARPI and/or docetaxel. I think that it is a work in progress in terms of optimal treatment selection, but the information is best collected at the very beginning.

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In patients receiving ADT and ARPI therapy, at least every 3 months we conduct routine laboratory testing with a PSA and a comprehensive metabolic panel to assess liver function and for metabolic abnormalities. In addition, ARPIs have potential drug-drug interactions with commonly prescribed medications, including cholesterol-lowering agents, antihypertensives, and blood thinners, so a close partnership with primary care is required while the patient is on ARPI therapy to consider dose reductions or substitutions, when necessary.

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PSA tends to be a reliable marker of prostate cancer disease progression. So, if a patient’s PSA level is declining and remains low, they are almost certainly responding to therapy. In most patients, a rise in PSA is the first indication of disease progression. That said, PSA is not perfect, but I think that there are opportunities to look for complementary ways of monitoring treatment response and resistance, including circulating tumor DNA and imaging.

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National guidelines suggest that imaging be performed on an intermittent basis in patients with mHSPC, and I think that this is reasonable for the vast majority of patients. I would say that imaging has 3 functions. One is to establish a new baseline, so, if the patient’s PSA level rises later, you will have a more appropriate contemporary comparison rather than just diagnostic imaging. Second is to identify the occasional patient who will have progression despite a low PSA level. This is not very common, but it is important when you find it. I have the greatest interest in looking for that in patients who have a poor prognosis. And third is to restage the disease after some interval to help make decisions about patients who have a favorable prognosis for whom you might be considering treatment de-escalation.