<p><p>Treatment intensification can be more effective than ADT alone for metastatic prostate cancer. However, there is some confusion about when and in whom treatment should be intensified, leading some clinicians to still administer ADT alone despite evidence for widespread benefit with the addition of ARPIs.</p></p>

I can understand how the words “treatment intensification” may seem emotionally laden to patients because they might imply a disproportionate adoption of risk without benefit, since something that is intense sounds strong or potentially harmful. However, I think that, from a communications point of view, any terminology has its challenges. Although alternative terminology may be more precise, using a term such as “doublet” or “triplet” instead can be more problematic if it is not clear which doublet or triplet the health care provider is referring to.

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I add a second drug when it will cause more benefit than harm, which is what we all want to do. The guidelines primarily reflect disease characteristics, but we also have to think about the patient. Some patients with prostate cancer who have a low burden of disease may be very good candidates to receive 3-drug therapy because they have a particularly poor prognosis with a high risk of cancer-specific mortality due to their young age and good overall health. Some disease distinctions (ie, de novo vs recurrent) may reflect biologic differences in the cancer. I think that we will have a better understanding of the biology as time goes on, and I hope that tumor genetic testing will be incorporated into disease distinction considerations so that we can make more precise treatment recommendations for the patient in front of us.

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There was a period when the common view was that you should only intensify therapy with the addition of docetaxel in patients with a high burden of disease. I think that this concept carried forward with the development of ARPIs, regardless of evidence of benefits across a much broader spectrum of metastatic disease. The biggest impact that we might be able to make on the field currently is by adopting the evidence that we already have. Unfortunately, one of the most commonly administered treatments remains ADT monotherapy, despite consistent evidence across studies of improved overall survival (OS) with the addition of ARPIs. The lack of consistent treatment with ARPIs in patients with metastatic prostate cancer is a poor reflection on our field.

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Most of the studies looking at the addition of ARPIs for metastatic castration-sensitive disease had a high rate of crossover. However, despite this, there were clinically meaningful improvements in OS. This basically excludes the possibility that the patient would derive the same benefits from waiting to receive the treatment later. The benefits of ARPIs appear similar to those of ADT in terms of improving progression-free survival and OS. ADT and ARPIs have somewhat different safety profiles, so we can individualize treatment decisions when necessary, but the benefits substantially outweigh the potential risks. I would much rather see a patient start treatment with ADT and an ARPI and then need to discontinue the ARPI than for them never to have started ARPI therapy. However, the vast majority of patients are able to tolerate these drugs long-term.