High PSA Before HIFU Tied to Increased Recurrence, Treatment Failure
High prostate-specific antigen levels before High-Intensity Focused Ultrasound were linked to higher recurrence and treatment failure in intermediate-risk prostate cancer.
Two prostate cancer cells in the final stage of cell division: ©PRB ARTS - stock.adobe.com
Research presented in a poster at the 2025 ASCO Genitourinary Cancers Symposium found that high prostate-specific antigen (PSA) levels before High-Intensity Focused Ultrasound (HIFU) were associated with a greater risk of overall recurrence and treatment failure in patients with intermediate-risk prostate cancer.
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 3 or higher (≥GG3) was associated with both in-field and overall recurrence on biopsy, while sexual (P = .36) and urinary (P = .28) 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 Kevin Shee, MD, 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.
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 adverse 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 (IQR, 59-72) were enrolled on the study. The median prostate volume of those enrolled was 36 cc’s (IQR, 28-48), the median PSA was 6.1 ng/ML (IQR, 4.4-8.3), and the median year of diagnosis was 2021 (IQR, 2018-2022). 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 Gleason Grade’s (GG) were GG2 (73%), GG3 (22%), and GG4-5 (5%). Moreover, the CAPRA clinical risk was low (44%), intermediate (59%), or high (8%); the MRI PI-RADS were 1-2 (8%), 3 (14%), or 4-5 (77%); and the genomic risk was low (63%) or high (37%). 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, Gleason grade (GG3+ vs GG2) was associated with higher recurrence risk (odds ratio [OR], 3.12; 95% CI, 1.05–9.29, P = .04). Additionally, PSA levels were also associated with higher recurrence (OR, 1.21; 95% CI, 1.06–1.39; P < .01). 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 (OR, 5.51; 95% CI, 1.48–20.46; P = .01).
For biopsy-proven in-field recurrence, Gleason grade remained a significant factor in both models; Model 1 showed an OR of 3.13 (95% CI, 1.14–8.59; P = .03) and Model 2 showed an OR of 3.01 (95% CI, 1.09–8.28; P = .03). Regarding treatment failure, PSA levels remained a predictor. In Model 1, higher PSA levels were associated with an increased risk of treatment failure (HR, 1.15, 95% CI, 1.06–1.25; P < .01). 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 (HR, 5.70; 95% CI, 1.69–19.28; P < .01).
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.”
