Sequential Imaging of Suspicion of Prostate Cancer: Reducing Overdiagnosis and Unnecessary Biopsy with Timely Diagnosis of Significant Cancer (SPROUT)-Prospective Multicentre Cohort Study Protocol

Overdiagnosis of clinically insignificant prostate cancer (International Society of Urological Pathology Grade Group 1 [ISUP GG1]) remains a concern. Many men with Prostate Imaging Reporting and Data System (PI-RADS 3) or selected PI-RADS 4 lesions have no cancer or only ISUP GG1 on biopsy. A strategy of deferred decision-making on biopsy indication using longitudinal information may reduce overdiagnosis and biopsy burden. The SPROUT trial evaluates longitudinal prostate-specific antigen density (PSAD) and magnetic resonance imaging (MRI) monitoring, triggering biopsy only upon progression while preserving safety for detecting clinically significant (ISUP GG ≥2) cancer.

The SPROUT study is a phase 2, multicentre, single-arm trial across seven Dutch centres, enrolling 503 biopsy-naïve men aged >18 yr with PI-RADS 3, or PI-RADS 4 with PSAD ≤ 0.15 ng/ml/cm³. Instead of immediate biopsy, participants undergo PSA testing every 6 mo and annual MRI for up to 4 yr. If follow-up MRI shows no suspicious lesion, monitoring de-escalates to twice-yearly PSA testing alone, with MRI retriggered in the event of subsequent biochemical progression. Targeted biopsies are triggered by progression to PI-RADS 4 with PSAD >0.15 ng/ml/cm³ or PI-RADS 5. Men with persistent PI-RADS 3 or 4 lesions after 48 mo undergo an end-of-study biopsy. Image quality is assessed using a standardised scoring system for Prostate Image Quality (PI-QUAL) version 2.

Primary endpoints are the proportion of avoided biopsies that would have been negative or ISUP GG1 (effectiveness), and the proportion of ISUP GG ≥ 2 cancers missed by monitoring, using the end-of-study biopsy as the reference (safety). Secondary endpoints include grade shifts, detection of ISUP GG ≥ 3, health-related quality of life (EPIC-26, short STAI-6), and cost-effectiveness.

Safety will be assessed using a ≤5% noninferiority margin for missed ISUP GG ≥ 2 cancers, defined as cases detected only at end-of-study biopsy. Effectiveness will be measured by ISUP GG1 and negative biopsy rates.

Strengths include the intermediate-term follow-up and MRI quality control during the study. Limitations include the nonrandomised design, which might result in selection bias.

This trial was approved by the Medical Research Ethics Committee Utrecht (ClinicalTrials.gov, NCT07180381).

Not all prostate cancers require treatment. This study focuses on men with an intermediate risk of harbouring aggressive prostate cancer, based on PSA blood levels and MRI findings. Instead of undergoing immediate prostate biopsy, participants are closely monitored with PSA testing every 6 mo and MRI annually over a 4-yr period. A biopsy is performed only if there are signs of disease progression. If no biopsy has been performed during the study but a lesion remains visible on the final MRI, end-of-study biopsies will be conducted to assess any potentially missed aggressive cancers. This approach aims to reduce unnecessary biopsies and avoid overdiagnosis of nonaggressive prostate cancers, while still ensuring timely detection of cancers that require treatment.