While novel hormonal therapies (NHT) have revolutionized androgen deprivation therapy (ADT) for metastatic castration-sensitive prostate cancer (mCSPC), the optimal intensification of treatment remains a challenge. Existing studies have primarily relied on claims data, limiting the understanding of treatment patterns in de novo mCSPC patients and the influence of disease burden on treatment decisions. Now, a retrospective study presented at the 2023 ASCO Annual Meeting has shed light on the real-world baseline characteristics and first-line treatment patterns in patients diagnosed with de novo mCSPC, categorized by disease volume.
In the current study, Freedland and colleagues aimed to address these gaps by analyzing baseline characteristics and first-line treatment approaches in patients with high-volume (HV) versus low-volume (LV) de novo mCSPC (Abstract e17081). The analysis utilized the VA Informatics and Computing Infrastructure to identify adult men diagnosed with de novo mCSPC between February 2018 and June 2020. The disease volume was categorized as HV or LV based on the CHAARTED trial (NCT00309985) criteria. Clinical chart review confirmed the diagnosis and treatment initiation, which included ADT alone, ADT with first-generation non-steroidal anti-androgens (NSAA), or ADT with NHT. Baseline characteristics and first-line treatment data were analyzed descriptively.
Among the 380 de novo mCSPC patients reviewed, 57 percent had HV disease, while 43 percent had LV disease. The mean age was comparable between HV (74.5 years) and LV (75.2 years) cohorts. The distribution of Black and White patients was similar in both cohorts, with 34 percent and 35 percent being Black and 66 percent and 65 percent being White, respectively. Baseline data showed that HV patients had higher median prostate-specific antigen levels (153.1 ng/mL vs. 73.8 ng/mL) and alkaline phosphatase levels (192.0 IU/L vs. 106.0 IU/L) compared to LV patients.
Notably, HV patients were less likely to have diabetes and cardiovascular comorbidities compared to LV patients, while the distribution of Charlson Comorbidity Index scores was similar between the two cohorts (mean [SD]: 4.4 [3.1] vs. 4.2 [3.1]). Among patients with bone metastases only, HV patients had a significantly higher proportion (65%) of "too numerous to count" bone metastases, whereas LV patients accounted for only 9 percent. Although HV patients had slightly higher utilization of ADT+NHT (35%) compared to LV patients (27%), the most common first-line treatment in both cohorts was ADT+/-NSAA. The median duration of first-line treatment was shorter in HV patients (286 days) compared to LV patients (358 days).
Oncology Times connected with lead study author, Stephen Freedland, MD, at Cedars-Sinai for additional insights into their research. He is Director of the Center for Integrated Research in Cancer and Lifestyle, Co-Director of the Cancer Genetics and Prevention Program, and Associate Director for Faculty Development at the Cancer Institute. He is also a faculty physician in the Division of Urology of Cedars-Sinai Surgery Department at Cedars-Sinai Medical Center, Los Angeles.
Oncology Times: What factors may contribute to the underutilization of treatment intensification in patients with de novo mCSPC, regardless of disease burden, as indicated by the study findings?
Freedland: "This is a complex question for which there is no easy answer. Guidelines are quite clear about what we should be doing and yet study after study shows that a large percentage of men are not getting treatment intensification. For this study, the years were 2018-2020. 2018 was early in the intensification era and the data were not as strong. Even when new data is released, it takes a while for all care providers to become aware and implement changes to their practice. Thus, I would say a lack of knowledge of the data is a key driver along with clinicians' and patients' preferences for treatment.
"Another factor that likely plays a role is that standard treatment (ADT alone) works well in reducing PSA levels. Thus, many physicians may think this is sufficient. Finally, there are both financial barriers (not as much an issue in the Veterans Health Administration) and clinicians' perceptions about tolerability. Treatment intensification does come with more side effects. Overall, these effects are modest given the impressive improvements in survival, but for some, this may be enough to prevent them from using these agents."
Oncology Times: Based on the retrospective analysis of real-world data, what are the key implications for clinical practice and future research regarding the optimal treatment approach for patients who have de novo mCSPC, and how can treatment intensification be improved to meet the unmet needs of these patients?
Freedland: "We know, across many studies, that treatment intensification by adding either novel hormonal therapies, chemotherapy, or both to standard ADT improves survival. Herein, we see, yet again, the uptake of this is far from ideal in real-world studies. Thus, research needs to pinpoint the exact reasons. There are likely multiple reasons, and the reasons may vary from provider to provider and patient to patient.
"One key barrier, in my opinion, is provider knowledge. Thus, we, as a community, need to better educate physicians and care providers about the dramatic survival benefits of these treatments. We also need to educate them about the side effects and how to manage the side effects. Once someone knows how to assess and manage a side effect, it no longer seems so scary. Thus, education needs to play a major role in improving these practice patterns.
"Going forward, other questions will arise, particularly in that many metastases are being diagnosed via PSMA. Does a PSMA+ lesion require the same level of intensive therapy? What if someone undergoes metastases-directed therapy-do they need any systemic therapy and, if so, how and for how long? Understanding patterns in this ever-changing world can help us identify what is happening in the real world, what the gaps are and, hopefully, the best treatment approaches to optimize both quality and quantity of life."
Dibash Kumar Das is a contributing writer.