A Phase I Trial of Neoadjuvant Stereotactic Body Radiotherapy Prior to Radical Prostatectomy for Locally Advanced Prostate Cancer

Purpose: Men with locally advanced prostate cancer who undergo radical prostatectomy (RP) often develop recurrence and require post-operative radiotherapy. We aimed to determine the safety of neoadjuvant stereotactic body radiotherapy (SBRT) prior to RP in this population.

Patients and Methods: A single institution phase I trial (NCTXXXX) of men with high-risk or node positive prostate cancer enrolled between 3/2017-10/2017. The primary endpoint was to determine the maximum tolerated dose of SBRT based on a composite 30-day post-RP toxicity goal of ≤28% of patients experiencing a dose-limiting toxicity (DLT). Secondary outcomes included toxicity, efficacy, and multiple quality of life (QoL) inventories. SBRT (30-35 Gy/5 fractions) was delivered to the prostate and seminal vesicles, and 25 Gy/5 fractions to the pelvic lymph nodes. RP was performed a median of 6 weeks post-SBRT. Hormone therapy was not allowed.

Results: Median follow-up was 40 months (range, 33-44). Twenty-five percent of patients (n=4) experienced a DLT within 30-days post-RP, however the trial was stopped early (n=16 of planned 38 patients) due to the proportion and severity of late adverse events. Post-RP grade 3 genitourinary and gastrointestinal toxicities occurred in 75% (n=12) and 25% (n=4) of patients, respectively. Two patients required cystectomy and urinary diversion ≥2 years post-RP. At 24-months post-RP, 75% (n=12) of men used ≥1 pad/day and 0% had erections suitable for intercourse. Surgical margins were negative in all patients, and 31% (n=5) had complete or partial (pre-RP) MRI-response to SBRT. Three-year biochemical recurrence and distant metastasis were 45% (95%CI 5-68%) and 28% (95%CI 0-49%), respectively.

Conclusion: Neoadjuvant SBRT followed by RP resulted in unacceptably high toxicity and severe QoL declines.

Liat Hammer, MD, PhD,1 Ralph Jiang, MA,2 Jason Hearn, MD,1 Jack Lashbrook,1 Amyre Mitchell, NP,1 Stephanie Daignault-Newton, MS,3 Robert T Dess, MD,1 William C Jackson, MD,1 Zachery Reichert, MD, PhD,4 Joshi J. Alumkal, MD,4 Samuel Kaffenberger, MD,5 Arvin George, MD,5 Jeffrey Montgomery, MD,5 Simpa S. Salami, MD, MPH,5 Todd M. Morgan, MD,5 David Miller, MD, MPH,5 Daniela Wittman, PhD, LMSW,5 Brent Hollenbeck, MD,5 Rohit Mehra, MD,6 Matthew S. Davenport, MD,7 Yilun Sun, PhD,8 Matthew Schipper, PhD,8 Ganesh Palapattu, MD,5 Daniel E. Spratt, MD1,9

  1. Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA
  2. Department of Biostatistics, University of Michigan, Ann Arbor, MI, USADepartment of Biostatistics and the Department of Urology, University of Michigan, Ann Arbor, MI, USA
  3. Department of Medicine, University of Michigan, Ann Arbor, MI, USA
  4. Department of Urology, University of Michigan, Ann Arbor, MI, USA
  5. Department of Pathology, University of Michigan, Ann Arbor, MI, USA
  6. Departments of Radiology and Urology, University of Michigan, Ann Arbor, MI, USA
  7. Department of Biostatistics and the Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA
  8. Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Cleveland, OH, USA

Source: Hammer, L., Jiang R., Hearn J. et al. A Phase I Trial of Neoadjuvant Stereotactic Body Radiotherapy Prior to Radical Prostatectomy for Locally Advanced Prostate Cancer. Internation Journal of Radiation Oncology. 2022. DOI: https://doi.org/10.1016/j.ijrobp.2022.07.016
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