Current treatment for prostate cancer has become much more tailored compared with treatment in the past. Previously, we would use the same treatment approach for large groups of patients. However, as a result of a greater understanding of pathology and advances in both molecular imaging and genomic sequencing, we now have more insight into an individual’s disease biology. Instead of using rigid operational definitions for groups of patients who should receive the same treatment, we are going to see treatment selection and sequencing that is much more refined and specific to each individual patient. As such, I think that we will see the development and expansion of individual paradigms that match well with individual genomic characteristics and the extent of disease.

Regarding the role of focal/ablative techniques and their place in the spectrum of disease, the primary tumor is typically not the source of resistance in CRPC. It is in a limited subset of patients, but most individuals who experience recurrence/progression do so distantly rather than locally. Some individuals may experience local progression that might require ablative therapy, radiation-targeted therapy, focal high-intensity–focused ultrasound, cryotherapy, or surgery, but the focus has been more on the distant disease.

That said, with prostate-specific membrane antigen (PSMA) positron emission tomography, we are beginning to identify an oligometastatic disease state in which the issue of focal treatment for limited metastatic disease is highly relevant (eg, stereotactic body radiation therapy for oligometastases might help to improve outcomes). We have gained new insights into the metastatic involvement of lymph nodes from PSMA-based imaging. My clinic is conducting a phase 1 trial using an intra-operative PSMA fluorophore and an advanced Firefly camera to guide surgery. Initial results show that this approach is well tolerated, and I envision that it will be integrated fairly quickly into clinical practice for high-risk patients who are undergoing surgery or for those who previously underwent surgery or radiation therapy and currently have lymph node–only disease.

When I see a patient with CRPC, I begin thinking about not only my initial treatment but also the whole treatment sequence, because none of these treatment modalities alone are curative in this setting. Our goal is to extend the patient’s life for as long as possible with the best quality of life throughout that period.

I try to explain to my patients that each of these therapies is a bridge to another, and our goal is to determine the best sequence of therapy for them. Studies are beginning to evaluate this. I think that it is very significant that we are able to show that switching from one hormonal therapy to another is not particularly effective. It is important that clinicians are aware of this message, as these practices still exist. In contrast, one cytotoxic therapy after another often does offer benefit. Thus, we really need data to direct us to the optimal treatment sequences. We cannot assume that the same treatment sequence is best for all patients. 

When it comes to matching the right treatment with the right patient, an individual’s comorbidities and level of treatment tolerance must be considered. For instance, not all patients are candidates for chemotherapy. However, with the numerous dosing regimens available, most can tolerate at least some degree of chemotherapy. So, I would not categorically rule out chemotherapy based purely on a patient’s age or the presence of comorbidities.

A lot of this comes down to understanding the big picture for each patient. We need to understand how we can modify our regimens to make them tolerable for these individuals while they are still functional. Finally, we need to help patients understand that the goal is to keep them functional and symptom free for as long as possible.

In the treatment of metastatic prostate cancer, if hormones are used early and often, patients will likely experience better outcomes. In general, these therapies are fairly well tolerated, and these well-tolerated, orally administered agents are going to be the treatments that are typically used first line. That is what I do in my practice. The good news is that studies evaluating hormone combinations for metastatic disease have reported tremendous improvements in survival, with metastatic patients living 6 to 7 years. As things evolve, I believe that we will be able to extend life expectancy even longer by bringing newer therapies up front so that they are given earlier in the disease course.

However, when looking beyond hormone treatment, there are differences of opinion. Should we use immunotherapy? Bone-targeted radium-223? Chemotherapy? We now also have precision medicine agents that are targeted toward specific genomic alterations, such as homologous recombination repair defects, which are indicated in that post-hormone space. For example, olaparib has been approved for patients who have the genomic alterations that are favorable for an olaparib response. There is also PSMA-targeted radioligand therapy.

The armamentarium is becoming crowded, but that is a great problem to have. There is nothing that patients and oncologists like more than options. I think that we are going to be tailoring these therapies to the patient the best way that we know how and that we will really begin to look at combinations of therapies more. We currently have combination therapy with androgen deprivation agents and abiraterone, and there will be more trials of combination therapies. It is still a bit tricky and there is still a lot of controversy, but we are making progress. For me, the more options, the better.