October 22, 2023
Exploring the Influence of Ultra-Low PSA in Prostate Cancer Treatment
By Dibash Kumar Das, PhD
In the realm of metastatic castration-sensitive prostate cancer (mCSPC) treatment, the integration of novel therapies and precision medicine has been a game-changer. A recent study, presented by Chowdhury, et al, sheds light on the remarkable influence of rapid ultra-low prostate-specific antigen decline (UL PSA) in mCSPC patients undergoing treatment with apalutamide (APA) in combination with androgen deprivation therapy (ADT).
In the TITAN trial (NCT02489318), mCSPC patients treated with a combination of APA and ADT experienced a rapid and deep prostate-specific antigen (PSA) decline of ≤0.2 ng/mL within 3 months of treatment initiation. This decline was associated with significant improvements in overall survival (OS). Building on this intriguing observation, new research presented at the European Society for Medical Oncology (ESMO) Congress 2023, held in Madrid, Spain, aimed to explore the effects of UL PSA on various clinical outcomes (Abstract 1786P).
The study analyzed data from 525 patients receiving 240 mg/day of APA and 527 patients receiving a placebo (PBO) in conjunction with ADT. Two distinct UL PSA groups were examined: 1) those with PSA levels >0.02 to ≤0.2 ng/mL (UL1) and those with PSA levels ≤0.02 ng/mL (UL2). The analysis focused on their association with OS, radiographic progression-free survival, time to castration resistance, and time to PSA progression, employing landmark analysis, the Kaplan-Meier method, and Cox proportional hazards modeling.
The results revealed significant insights into the effect of UL PSA during the study. It was found that 49 percent of APA-treated patients and 17 percent of those on PBO achieved UL2 PSA values. By 3 months, UL1 and UL2 were observed in 38 percent and 23 percent of APA patients and 15 percent and 5 percent of PBO patients. At 6 months, these values changed to 29 percent and 36 percent (APA) and 17 percent and 6 percent (PBO).
Patients treated with APA who achieved UL1/UL2 PSA at 3 months had lower baseline PSA levels and a higher percentage of low-volume disease compared to those with PSA levels >0.2 ng/mL. Patients who reached UL1/UL2 PSA at 3 or 6 months experienced improved long-term outcomes, irrespective of disease volume. Importantly, volume-adjusted outcomes were significantly enhanced in patients achieving UL1/UL2 at 3 months or 6 months.
At 42 months of follow-up post-landmark analysis, survival rates demonstrated the profound impact of UL PSA decline. The survival rate was 89 percent (UL2 achieved at 3 months), 81 percent (UL2 achieved after 3 months), and 34 percent (never achieved UL2 after 3 months). A similar trend was observed at 6 months. Patients achieving UL1, UL2, or none of these at any time exhibited survival rates of 59 percent, 92 percent, and 33 percent, respectively.
Importantly, “the safety profile of APA across PSA response subgroups and between treatment groups was consistent with previous reports. Treatment-emergent adverse events by PSA declined at 3 months,” according to study author, Neeraj Agarwal, MD, Professor of Medicine and Presidential Endowed Chair of Cancer Research at the Huntsman Cancer Institute (HCI), University of Utah. He also directs the Genitourinary Oncology Program and the Center of Investigational Therapeutics at the HCI.
The TITAN trial's findings underscore the significance of UL PSA decline in mCSPC patients receiving APA. Agarwal concluded that “it is important to take into consideration a broader view of what treatment success looks like for metastatic castration-sensitive prostate cancer patients with ultra-low PSA. These populations, when treated, showed improved outcomes compared with those who achieved PSA >0.2 ng/mL regardless of disease volume. Evaluation of treatment strategies, including treatment escalation and de-escalation trials, should continue to focus on rapid and deep PSA decline and how it will impact future options for prostate cancer patients.”
Dibash Kumar Das is a contributing writer.