Over the past decade, the development of advanced prostate cancer (PCa) treatment options has been nothing short of revolutionary, especially for those of us who trained in an era when androgen deprivation therapy (ADT) was all we had. When ADT failed, there was little else to do. Our options were high-dose steroids and ineffective chemotherapy. Now, we are blessed with a regimen of multimodality therapies, including bone health regimens, immunotherapies, androgen synthesis inhibitors, androgen receptor/pathway inhibitors, radiopharmaceuticals, and newer chemotherapies. At last estimate, there are more than 40 potential future therapies in phase 3 clinical trials, and new tests make it possible to genetically stratify patient’s disease and potentially identify genetic risks for their offspring and other relatives.
As a whole, this is a hopeful time for patients with PCa that is metastatic, castration resistant, or both. Newer therapies have significant survival advantages with relatively tolerable side effect profiles. With this growing menu of therapies, however, there is a growing challenge for clinicians to identify patients, organize care plans, and standardize treatment regimens for optimal benefit. It becomes confusing, perhaps even overwhelming, to manage all facets of advanced PCa care.
At Oregon Urology Institute (OUI) in Springfield, we continuously strive to optimize the care of patients with advanced PCa. We began years ago by first identifying all patients who were receiving ADT. We standardized a recommendation that all patients should be taking calcium and vitamin D3. We added a recommendation that patients undergo DEXA scans at ADT initiation, now also a Merit-based Incentive Payment System (MIPS) measure. Frequently, patients have below-normal bone density at the time of ADT initiation and, of course, with ADT this will tend to worsen without use of a bone-targeting agent. Identification of patients on ADT and addressing their bone health early leads to better selection of potential therapies for these patients in the future.
Recently, our group agreed that patients who progressed to metastatic disease or castration-resistant PCa (CRPC) should be referred within our group to providers with a special interest in advanced disease. Rather than each provider in our group having a handful of these patients, we feel the best care of these patients should be centered with a smaller subset of physicians who have an interest in keeping up with this rapidly changing landscape.
The most recent development this year is approval of 2 oral therapies for non-metastatic CRPC. These therapies have been shown to delay the development of metastases by about 2 years. Add this to new data that a patient who presents with newly diagnosed metastatic PCa should be considered for ADT plus either chemotherapy or an oral androgen synthesis inhibitor. Overall, these are good advances for patients, but they have increased the complexity of care and underscore the importance of establishing a baseline scan to confirm a patient does not have metastatic disease prior to treatment. In fact, studies have shown that more than 30% of men whom the clinician believed to have non-metastatic disease are confirmed to have metastases when imaging is performed.
There is evidence across many studies that early identification of advanced PCa patients for initiation of numerous therapies shows improved outcomes when compared with implementation of these therapies at later stages. This is particularly evident with immunotherapy, where patients with less bulky disease and before pain or other symptoms have developed show improved outcomes. In addition to the favorable side effect profile, data on immunotherapy have shown that when these therapies are deployed early, when the immune system is intact, patients live longer. In some cases this survival advantage extends beyond 1 year.1 This is also true of radiopharmaceutical therapy where the regimen extends over 6 months and late identification of the patient who is a candidate for this surgery may preclude the patient from completing the entire regimen of 6 infusions. Earlier is better.
Data analytics are an essential tool for identifying patients with CRPC and/or metastatic disease. Protocols for monitoring patients and a regular scanning cadence are essential to ensure patients receive the appropriate treatment for their disease state. Patients on continuous ADT who have 2 PSA rises from the nadir PSA should now be flagged as a new CRPC patient, and imaging should be considered. Use of next generation imaging, such as the fluciclovine F 18 PET/CT scan, can identify patients with early metastatic disease and allow us to initiate first-line treatment with immunotherapy as recommended by NCCN, RADAR II and UroGPO guidelines. Data analytics can also be used for tracking patients as they progress and aid in identifying patients who may benefit from a different or additional layered treatment. The idea is not always to treat every patient with every therapy, but to be proactive in the identification of patients so they can be considered for right therapies at the right time.
We are now beginning to add to our protocols genomic tests to identify variants that may dictate different treatment pathways. The information here is growing. We now also understand that, for example, BRCA testing in select patient groups may identify patients and related family members at higher risk of aggressive disease not only of PCa, but also breast, ovarian and pancreatic cancers. As urologists, we have heard of BRCA as it relates to women and breast cancer, but the link with our male patients with PCa is relatively new.
Many urology groups have a growing interest in treating advanced PCa, but getting started can be somewhat daunting. Inevitably, a urologist will start with one patient and prescribe one therapy and then as the patient usually progresses over time, this will lead to the recommendation of additional therapies. Of course, more patients will come along over time and the need for further standardization and operational growth will become necessary.
The most important factor is to remain focused on the best treatment path for each patient. The work here is gratifying and patients are clearly benefiting from the development of advanced prostate cancer clinics. All of this points to better outcomes for our patients, including many who had few options only a several years ago.
Bryan A. Mehlhaff, MD, is Medical Director of Research at the Oregon Urology Institute in Springfield and a former board member of the Large Urology Group Practice Association (LUGPA).
1 Schellhammer PF, Chodak G, Whitmore JB, et al. Lower baseline prostate-specific antigen is associated with a greater overall survival benefit from sipuleucel-T in the Immunotherapy for Prostate Adenocarcinoma Treatment (IMPACT) trial. Urology. 2013;81:1297-1302.