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Article

February 13, 2025

Elevated PSA Link to Higher Recurrence Risk in Intermediate-Risk Prostate Cancer

Author(s):

Ryan Scott

Fact checked by:

Spencer Feldman

Key Takeaways

  • High pre-treatment PSA levels correlate with increased recurrence and treatment failure in intermediate-risk prostate cancer patients treated with HIFU.
  • Gleason grade 3 or higher is associated with both in-field and overall recurrence, emphasizing its prognostic significance.
  • Sexual and urinary functions remain stable post-HIFU, suggesting minimal impact on quality of life.
  • Careful patient selection is crucial for HIFU, offering modest cancer control with minimal side effects for appropriate candidates.
SHOW MORE

Among those with intermediate-risk prostate cancer, high PSA levels prior to HIFU led to an increased risk of overall recurrence and treatment failure.

Illustration of body highlighting prostate area.

High pre-HIFU PSA levels in intermediate-risk prostate cancer were linked to increased recurrence and treatment failure, per ASCO 2025 research.

Among patients with intermediate-risk prostate cancer, high prostate-specific antigen (PSA) levels before treatment with a High-Intensity Focused Ultrasound (HIFU) had a link to an increased risk of overall recurrence and treatment failure, according to research published in a poster at the 2025 ASCO Genitourinary Cancers Symposium.

In this investigation of 108 men with intermediate-risk prostate cancer following HIFU, investigators found that in-field and overall recurrence on 1-year biopsy was 41% and 54%, respectively. Moreover, Gleason grade (GG) 3 or higher was associated with both in-field and overall recurrence on biopsy, while sexual and urinary function scores did not vary before vs after HIFU.

“Higher pre-HIFU PSA was associated with treatment failure and overall recurrence on biopsy, and GG3 [or higher] was associated with in-field and overall recurrence on biopsy, first study author Dr. Kevin Shee, and authors wrote in the abstract of the study.

Shee currently works in the Department of Urology, University of California, San Francisco (UCSF), UCSF Health, and is a Resident of Urology at the UCSF School of Medicine.

Glossary:

Gleason Grade: a number that describes how abnormal prostate cancer cells appear under a microscope.

High-Intensity Focused Ultrasound (HIFU): a non-invasive procedure that uses ultrasound waves to destroy abnormal tissue.

Prostate-specific antigen (PSA): protein in the blood that can indicate prostate cancer.

Breaking Down the Methods of the Research

Definitive therapy and active surveillance are both common ways to manage intermediate-risk prostate cancer. Although definitive treatments, such as radical prostatectomy or radiation therapy, are effective, they are often associated with significant side effects. For patients with favorable-risk disease, active surveillance may be an option, but this approach carries the risk of cancer progression over time.

Focal therapies selectively ablate cancerous tissue while minimizing the impact on quality of life, providing a more balanced approach. One such therapy is High-Intensity Focused Ultrasound (HIFU), which utilizes magnetic resonance imaging (MRI) and ultrasound to deliver high-frequency acoustic energy. Despite the potential benefits of HIFU, concerns regarding disease recurrence and progression to salvage treatment have limited its widespread adoption. To address investigators investigated pre-treatment characteristics associated with treatment progression and biopsy-confirmed recurrence following HIFU.

In investigation, male patients were eligible for enrollment if they had biopsy-confirmed intermediate-risk prostate cancer, had undergone HIFU at UCSF Health between 2021 and 2023, and had a one-year post-treatment biopsy. Eligible participants received a single ablative treatment using FocalOne HIFU, with ablation contours designed to maintain a 10mm margin around the tumor while sparing the nerves and urethra.

Key outcomes of interest included biopsy-confirmed recurrence, treatment failure requiring salvage therapy or indicating metastatic progression, and changes in urinary and sexual function.

A total of 108 men with a median age of 65 years were enrolled on the study. The median prostate volume of those enrolled was 36 cc’s, the median PSA was 6.1 ng/ML and the median year of diagnosis was 2021 . A majority of patients enrolled were White, (82%), though other races and ethnicities included were Asian/Pacific Islander (5%), African American (5%), and Mixed (8%).

Clinical T-stage of patients ranged from T1 (32%) to T2 (65%) and T3 (3%), while some were missing. The pre-HIFU GG were GG2 (73%), GG3 (22%), and GG4-5 (5%). Additionally, patients’ primary treatments were HIFU (56%) or active surveillance (44%).

Delving Into Further Findings

In Model 1, which evaluated continuous PSA, for biopsy-proven overall recurrence, GG grade (GG3+ versus GG2) was associated with higher recurrence risk, as were PSA levels. In Model 2, which categorized PSA levels, a PSA level greater than 10 ng/mL versus less than 6 ng/mL was also associated with increased recurrence risk. 

For biopsy-proven in-field recurrence, GG remained a significant factor in both models. Regarding treatment failure, PSA levels remained a predictor. In Model 1, higher PSA levels were associated with an increased risk of treatment failure. In Model 2, which was the categorical PSA model, PSA levels greater than 10 ng/mL versus less than 6 ng/mL were also linked to treatment failure.

Shee and study authors conclude the study’s abstract by stating: “These findings emphasize the importance of careful patient selection for HIFU, which has potential for modest cancer control with minimal side effects in the appropriate [patient with] intermediate-risk prostate cancer.”

Reference:

“Determining optimal patient selection for high-intensity focused ultrasound (HIFU) for prostate cancer: Results from a single-institution cohort” by Dr. Kevin Shee et al., Journal of Clinical Oncology.

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