Targeted Biopsy, Rapid Pathology, and Immediate Surgery in USTC High-Risk Prostate Cancer: A Prospective Multicenter Study

Study Design and Setting This is a prospective, multicenter, single-arm, open-label clinical study conducted in 12 tertiary hospitals in China that have established multidisciplinary prostate cancer teams.

Screening and Enrollment Male patients with clinical suspicion of prostate cancer undergo serum total PSA testing and 3.0T multiparametric MRI. Prostatic volume is measured to calculate prostate-specific antigen density (PSAD), and the index lesion is scored using PI-RADS v2.1. These parameters are entered into the USTC online nomogram (https://ustcprostatecancerprediction.shinyapps.io/dynnomapp/) to generate a predicted probability of clinically significant prostate cancer (csPCa). Patients with a predicted probability ≥0.60, who meet all eligibility criteria (PSA 4-100 ng/mL, at least one PI-RADS ≥3 lesion, ECOG 0-1, no contraindication to general anesthesia or radical prostatectomy, and no evidence of metastasis), are fully informed and asked to provide written consent. Enrolled participants proceed directly to the interventional pathway.

Intervention Under general anesthesia, MRI/ultrasound fusion targeted biopsy (2-4 cores from the index lesion) is performed. The cores are immediately submitted for frozen section hematoxylin-eosin staining and rapid immunohistochemistry (key antibodies: P63, P504s, CK5/6). A pathologist provides a report within 30-60 minutes.

If csPCa is diagnosed intraoperatively, the patient is repositioned and laparoscopic radical prostatectomy is completed under the same anesthesia session.

If rapid pathology returns benign tissue, atypical small acinar proliferation, high-grade prostatic intraepithelial neoplasia, or is non-diagnostic, the procedure is stopped; only the biopsy is performed, and further management follows standard care.

Endpoints and Follow-up Primary endpoints: Positive Predictive Value (PPV) of intraoperative frozen section combined with rapid immunohistochemistry for clinically significant prostate cancer (csPCa) Secondary endpoints: ① Positive surgical margin rate; ② Agreement rate between intraoperative rapid pathology and postoperative paraffin-embedded pathology according to the ISUP grading system. ② Biochemical recurrence rates at 3, 6, and 12 months postoperatively (defined as two consecutive postoperative serum PSA levels ≥ 0.2 ng/mL with an interval of at least 3 weeks; cumulative incidence will be calculated). ③ Incidence of perioperative complications. ③ Incidence of serious adverse events (SAEs). ④ Intraoperative blood loss (mL) and perioperative (intraoperative to 30 days postoperatively) transfusion rate. ⑤ Rehospitalization rate within 30 days postoperatively. ⑥ Urinary continence recovery rate at 3, 6, and 12 months postoperatively.

Follow-up visits occur at 30 days, 3, 6, and 12 months post-procedure. All data are captured via paper case report forms and managed centrally

• Positive surgical margin rate [Time frame: At the time of final paraffin pathology report (usually within 7-14 days after surgery)]
• Concordance of ISUP grade between intraoperative rapid pathology and postoperative paraffin pathology Concordance of ISUP grade between intraoperative rapid pathology and postoperative paraffin pathology [Time frame: At the time of final paraffin pathology report (usually within 7-14 days after surgery)]
• Perioperative complication rate [Time frame: Up to 30 days after surgery]
• Rate of serious adverse events (SAEs) [Time frame: From the day of surgery through 12 months of follow-up]
• Intraoperative blood loss and perioperative blood transfusion rate [Time frame: Intraoperative and up to 30 days after surgery]
• 30-day readmission rate [Time frame: 30 days after initial discharge]
• Urinary continence recovery rate Urinary continence recovery rate Urinary continence recovery rate [Time frame: 3, 6, and 12 months after surgery]