Study Validates PSA-Based Recurrence Definitions for Prostate Cancer Prognostication

A study recently published in The Prostate externally validated multiple biochemical recurrence definitions to predict treatment outcomes among patients with localized prostate cancer (PCa) following the use of high-intensity focused ultrasound (HIFU) as focal therapy.

For patients with PCa, follow-up visits involving scheduled biopsies or MRI can potentially become overwhelming, the study authors noted. Furthermore, MRIs are costly and come with their own obstacles related to access and technician variability, and prostate biopsies come with a risk of adverse events that necessitate hospitalization or medication. Finding a biomarker that is more reliable, cost-effective, and noninvasive would provide many benefits for patient care because clinicians could better anticipate treatment needs or outcomes.

Currently, postoperative prostate-specific antigen (PSA) levels are the preferred noninvasive biomarker in patient follow-ups, but sufficient criteria for predicting biochemical recurrence have not been outlined, the authors explained. Considering this, the researchers examined data from patients who underwent HIFU as their primary treatment for localized PCa to determine which of several PSA criteria are the most effective in detecting treatment failure after focal therapy.

The authors noted that the indications of HIFU and its advantages have not been fully established; however, previous studies have explored its usefulness as a treatment for localized PCa and found it may elicit similar outcomes to standard curative treatments such as prostatectomy and radiotherapy but with fewer treatment-related adverse events.

In the study, researchers compared multiple PSA-based biochemical recurrence definitions:

• PSA nadir
• time to PSA nadir
• percentage of PSA reduction
• Huber et al. criteria defined as PSA nadir + 1 ng/mL at 12 months or PSA nadir + 1.5 ng/mL at 24−36 months

Data from June 2001 through November 2020 were retrospectively gathered from patients who received HIFU at Jules Bordet Institute. The exclusion criteria included individuals without any visible lesions in their preoperative MRI, those who received androgen deprivation therapy (ADT) before treatment or who looked to HIFU as a salvage treatment, and those with metastatic PCa.

“Treatment failure” was defined as a postoperative PCa biopsy classified as ISUP grade group 2 (a scale in which higher grades indicate higher probability a patient’s cancer will spread); any need for salvage radical therapy such as radiotherapy or radical prostatectomy; the need for systemic treatment; devleopment of metastases; or death related to PCa.

A total of 178 patients were eligible for inclusion, 62% of which were classified as ISUP group 1, and 26% as ISUP group 2 at the time of preoperative biopsy. The median follow-up after treatment was 52 months.

Patients in the final analysis had a median PSA nadir of 1 ng/mL, median time to PSA nadir of 3 months, and percentage of PSA reduction of 85. The Huber et al. criteria proved highly effective and registered the best Harrell’s concordance-index (c-index) for predicting the necessity of further treatment (HR, 10; 95% CI, 4.5-22; P < .001; c‐index, 84%) and treatment failure (HR, 9.1; 95% CI, 3.3-25; P < .001; c‐index, 82%) following HIFU.

In total, 61 (34%) of patients needed additional treatment within a median of 24 months (range, 12-24). Additionally, 41 (23%) of patients experienced treatment failure within a median of 26 months. When analyzing the need for additional treatment and the rate of failure-free survival at 60 months, the overall cohort had rates of 89% and 98%, respectively, vs 26% and 49% of patients who met the Huber et al criteria.

The authors found that the Huber et al. criteria gave the most accurate predictions for treatment failure or additional treatment need after the use of HIFU for localized PCa. While they recognize that the single-center nature of their study and high proportion of ISUP grade 1 individuals could introduce potential biases, their results strengthen reports from previous studies on this subject. They hope that their exploration of the impact of Huber et al. criteria can serve as a useful guide for clinicians’ approaches to patient treatment and help determine when MRI or prostate biopsies are needed.

Reference

Mattlet A, Limani K, Alexandre P, Hawaux E, et al. External validation of biochemical recurrence definition to predict oncologic outcomes following focal therapy for localized prostate cancer using high intensity focused ultrasound. Prostate. Published online August 13, 2023. doi: 10.1002/pros.24614