ASCO GU 2025: Impact of Physicians’ Awareness of Prostate-Specific Antigen Doubling Time on Treatment Decisions in High-Risk Biochemically Recurrent Prostate Cancer

(UroToday.com) The 2025 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Annual Symposium held in San Francisco, CA between February 13–15, 2025 was host to prostate cancer poster session. Dr. Alicia Morgans presented the results of a study evaluating the impact of physicians’ awareness of prostate-specific antigen doubling time (PSADT) on treatment decisions in high-risk (HR) biochemically recurrent (BCR) prostate cancer (PCa).

PSADT is one of the strongest predictors of outcomes in patients with BCR PCa and a criterion for defining HR BCR, non-metastatic hormone-sensitive PCa (nmHSPC).¹ Given new treatment recommendations specific to patients with HR BCR nmHSPC (i.e., enzalutamide, based on the EMBARK study),^2-4 the determination of PSADT is of even higher importance in today’s clinical practice. However, it is unclear whether physicians routinely calculate and document PSADT in electronic medical records (EMRs) and how this influences treatment in routine practice.

This was a retrospective, observational, multisite, physician-abstracted medical chart review using existing EMR data from the Cardinal Health Oncology Provider Extended Network in the United States (January 1, 2018–December 12, 2022). This study included adult patients with HR BCR nmHSPC, defined as per the EMBARK trial criteria:

• PSADT ≤9 months with prostate-specific antigen (PSA) level ≥1 ng/mL for patients with a prior radical prostatectomy (with or without postoperative radiotherapy) or ≥2 ng/mL above the nadir for patients who had radiotherapy without prior radical prostatectomy

The index date was defined as date of HR BCR nmHSPC diagnosis (PSADT ≤9 months), occurring between January 1, 2018, and December 31, 2020. Follow-up was defined as the time from index date until disease progression, last follow-up (≥12 months), end of the study period, or death, whichever occurred first. The data abstraction period ranged from October 31, 2022, to December 12, 2022. 

With regards to PSADT identification, physicians reported PSADT in electronic case report forms (eCRFs) using doubling time from labs, clinical judgement, or an online calculator—these values were used for the known PSADT (kPSADT) group in subsequent analyses. If not provided in the eCRF, PSADT was assumed to be unavailable and, thus, unknown to the physician when treating the patient. In these cases, PSADT was retrospectively calculated based on physician-reported PSA values up to the index date, using the Memorial Sloan Kettering Cancer Center PSADT calculator.⁵ These calculated values were used for the unknown PSADT (uPSADT) group in subsequent analyses. For patients with kPSADT as well, PSADT was retrospectively calculated (using the same method as for uPSADT) to assess any discrepancy between physician-reported and retrospectively calculated PSADT.

With regards to statistical methods, baseline patient characteristics and treatment patterns were described and comparisons between the kPSADT and uPSADT groups were explored using chi-square tests and t-tests for categorical and continuous variables, respectively. Time to first treatment within 60 days after index was compared between the kPSADT and uPSADT groups using the Kaplan–Meier method. Discrepancy between physician-reported and retrospectively calculated PSADT values within the kPSADT group was assessed using a scatter plot. All comparisons were exploratory in nature with no power considerations.

This study included 284 patients (with chart reviews abstracted by 32 physicians), of whom 37% had kPSADT (abstracted by 14 physicians) and 63% had uPSADT (abstracted

by 24 physicians). Patients with kPSADT were older than those with uPSADT. Compared to patients with uPSADT, a higher proportion of patients with kPSADT had some characteristics of more aggressive disease, including a time from PCa diagnosis to BCR of <2 years, a Gleason score ≥8, an Eastern Cooperative Oncology Group performance status (ECOG PS) score ≥1, as well as higher PSA levels at nmHSPC and HR BCR diagnoses. However, patients with kPSADT also had some characteristics of less aggressive disease: more patients in this group had a longer PSADT at index of >3 to ≤9 months, whereas more patients with uPSADT had a shorter PSADT of ≤3 months.

The median time from index to end of follow-up was 30 months for the total study population, 26 months for the kPSADT group, and 32 months for the uPSADT group. The proportion of patients that received treatment within 60 days of index in the kPSADT group was >3-fold higher than that in the uPSADT group (64% versus 17%; p<0.001), with a significantly shorter median time to treatment (1 vs 6.7 months; hazard ratio [HR]: 3.4; 95% confidence interval [CI]: 2.6–4.4; p<0.0001; Figure 1).

The type of treatment received within 60 days after index varied significantly between the groups (p<0.001):

• A higher proportion of patients with kPSADT received:
  • Androgen-deprivation therapy (ADT) + androgen receptor pathway inhibitor (27% vs 1%)
  • ADT only (14% vs 8%)
  • ADT + radiation +/- nonsteroidal antiandrogen (8% vs 1%)
• A higher proportion of patients with uPSADT received observation only (83% vs 37%)
• The same proportion of patients with kPSADT and uPSADT received external beam radiation therapy only (6% vs 6%)

What about discrepancies between physician-reported and retrospectively calculated PSA in the kPSADT group? 88% of physician-reported kPSADTs were overestimated (i.e., longer) in comparison to a retrospective calculation of the PSADTs, potentially leading to underestimation of tumor aggressiveness and risk of metastasis for a majority of patients (Figure 2). Compared with the retrospectively calculated PSADTs, physician-reported kPSADTs were overestimated by 1 to <3 months in 36% of patients and by ≥3 months in 33% of patients. 11% of physician-reported kPSADTs were underestimated compared with the retrospectively calculated PSADTs.
Dr. Morgans acknowledged potential limitations to this study:

• Unreported PSADT values were assumed to be unknown by the physician based on their eCRF input; however, PSADT may have been calculated but not provided in the eCRF
• Discrepancies in reported PSADT values may exist due to variation in the methods used by physicians to assess PSADT (e.g., gestalt vs actual calculation)
• The analyses presented in this study were based on a small sample size of physicians and mostly descriptive in nature, and time to treatment was not adjusted for by baseline patient characteristics

Dr. Morgans concluded her presentation as follows:

• PSADT was unknown by the treating physician for nearly two-thirds of patients at the time of HR BCR nmHSPC diagnosis.
• Physicians more commonly calculated PSADT for patients who were older; had a shorter interval between PCa and biochemical recurrence; and had higher Gleason scores, ECOG PS scores, and baseline PSA levels.
• This suggests that physicians might have calculated PSADT for patients whom they considered to be at high risk for other reasons.
• When physicians knew PSADT, it was often overestimated when compared with a retrospective calculation of the PSADT.
• This overestimation of PSADT suggests that physicians underestimated tumor aggressiveness and risk of progression.
• A greater proportion of patients received treatment within a shorter timeframe when PSADT was known than when it was unknown.
• Many patients with HR BCR nmHSPC may remain unidentified in clinical practice. Greater use of formal PSADT calculators and documentation of PSADT by physicians could improve rates of treatment intensification and time to treatment, contributing to better outcomes for patients with HR BCR nmHSPC.

Presented by: Alicia K. Morgans, MD, MPH, Associate Professor, Department of Medicine, Medical Director of the Survivorship Program at Dana-Farber Cancer Institute, Massachusetts General Hospital, Boston, MA 

Written by: Rashid K. Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025.  

Related content: Improving PSA Doubling Time Calculation for High Risk Biochemical Recurrence - Alicia Morgans

1. Shore ND, Moul JW, Pienta KJ, et al. Biochemical recurrence in patients with prostate cancer after primary definitive therapy: treatment based on risk stratification. Prostate Cancer Prostatic Dis. 2024; 27(2):192-201.
2. Freedland SJ, de Almeida Luz M, De Giorgio U, et al. Improved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer. N Engl J Med. 2023; 389(16):1453-1465.
3. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V.1.2025. ©National Comprehensive Cancer Network, Inc. 2025. https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459. Access on February 13, 2025.
4. © European Association of Urology. EAU - EANM - ESTRO - ESUR - ISUP - SIOG Guidelines on Prostate Cancer. https://d56bochluxqnz.cloudfront.net/documents/full-guideline/EAU-EANM-ESTRO-ESUR-ISUP-SIOG-Guidelines-on-Prostate- Cancer-2024_2024-04-09-132035_ypmy_2024-04-16-122605_lqpk.pdf.
5. Memorial Sloan Kettering Cancer Center. PSA Doubling Time. Accessed February 13, 2025. https://www.mskcc.org/nomograms/prostate/psa_doubling_time.