Neoadjuvant therapies for surgical management of high risk, localized prostate cancer

Along with external beam radiation therapy (XRT) with concomitant androgen deprivation therapy (ADT), radical prostatectomy (RP) is a first-line treatment for high-risk, clinically localized prostate cancer. These patients have negative staging exams (e.g., nuclear bone scan, cross sectional imaging) and presumed local or loco-regional disease. Goals of surgical treatment are cure through eradication of macro- and microscopic cancer, pathological staging to determine the need for adjuvant therapies such as pelvic XRT +/？ ADT, and local control to reduce risk of urinary tract obstruction, gross hematuria, etc. should the patient develop advanced disease. High-risk disease is conventionally defined using D’Amico criteria, which include prostate-specific antigen (PSA) ≥20 ng/dL, Gleason score 4+4=8 (Grade group 4) or higher, and clinical stage ≥T2c. These patients often have aggressive disease phenotypes, reflected in greater risk of metastatic progression and death without treatment, greater risk of recurrence following local treatment, and greater need for adjuvant or salvage therapies (1,2). While traditionally XRT + ADT has been used for high risk patients based on concern for the ineffectiveness of surgery, RP has been increasingly used for localized, high risk disease (3,4) with principles of wide resection and extended lymphadenectomy to achieve the objectives detailed above. Retrospective series have demonstrated the effectiveness of surgery similar to XRT (5)