There is no question that a prolonged MFS is meaningful to patients with advanced prostate cancer. Avoiding metastatic disease is a primary goal for both patients and clinicians, and MFS is an important end point, particularly for those starting treatment at early stages of the disease. In the analysis by Xie et al, MFS was a strong surrogate of overall survival in localized prostate cancer, and, certainly, if you can avoid metastasis, you want to. However, simultaneously avoiding both metastasis and overtreatment can be challenging. This is where the wisdom of clinicians and listening to patients become important. The issue of overtreatment and undertreatment exists for all stages of prostate cancer. We used to think that these concerns were limited to men with clinically localized disease at presentation, but we now know that, whether it is the use of androgen deprivation therapy, salvage therapy, secondary therapy, or tertiary therapy, you can both overtreat and undertreat. So, you look at not just the disease state, but also the extent of disease, its molecular characterization, the velocity of progression, and patient factors (eg, performance status, comorbidities, individual preferences). 

I am at a major medical cancer center, and most of my patients are very well educated by the time I see them. They have been to multiple providers, and they understand the landscape. Some patients who are feeling well, and even some patients with more advanced disease whose pain is currently being managed appropriately, may prefer to forgo additional treatments based on their comorbidities and the expected burden of additional therapy. Others may be ideal candidates for a trial  of a novel anti-androgen such as apalutamide, enzalutamide, or darolutamide. All 3 agents were approved by the US Food and Drug Administration on the basis of prolonging MFS in patients with nonmetastatic castration-resistant prostate cancer. Important differences between these agents may exist in terms of tolerability, and these differences should be further explored and demonstrated.