A new real-world analysis from the IRONMAN registry confirms that achieving an undetectable PSA nadir (<0.2 ng/mL) within the first year of treatment is strongly associated with improved outcomes for patients with metastatic hormone-sensitive prostate cancer (mHSPC).

While intensified treatment with androgen receptor pathway inhibitors (ARPIs) and/or docetaxel has been shown to improve survival in clinical trials, this study provides real-world evidence on how PSA responses vary across treatment regimens and their impact on disease progression.

The study included 1,377 patients from the United States, Canada, Spain, and England who were treated with ADT monotherapy (n=375), ADT + ARPI (n=775), or ADT + docetaxel (n=227) between 2017 and August 2023. Patients receiving triplet therapy (ADT + ARPI + docetaxel) were excluded due to small numbers.

At 6 months, 40% of patients overall achieved PSA nadir <0.2 ng/mL, while by 12 months, this increased to 51%.

However, PSA response rates varied by treatment:

At 6 months: 51% of patients on ADT + ARPI reached an undetectable PSA nadir. Only 27% of those on ADT monotherapy and 26% on ADT + docetaxel achieved the same.

At 12 months: The highest PSA suppression rate was seen in the ADT + ARPI group (63%). ADT monotherapy and ADT + docetaxel lagged behind at 38% and 32%, respectively.

With a median follow-up of 18 months, 291 patients (21%) experienced disease relapse, with 19% showing PSA progression (a PSA increase of ≥25% from nadir and an absolute rise of >2 ng/mL).

When dividing patients based on whether they reached PSA nadir <0.2 ng/mL at 6 months, those who achieved this milestone had lower rates of disease relapse at 12, 24, and 36 months across all treatment groups.

This reinforces prior clinical trial findings that early deep PSA responses are linked to better long-term outcomes.

In a nutshell:

• ADT + ARPI leads to the highest rates of undetectable PSA nadir, outperforming ADT alone or ADT + docetaxel in achieving deep PSA suppression at both 6 and 12 months.
• Patients who reach PSA nadir <0.2 ng/mL within 6 months have lower relapse rates, emphasizing the importance of early PSA monitoring.

Real-world data aligns with clinical trials, confirming that PSA nadir is a valuable predictor of treatment success in mHSPC.

Source.