AUA 2018: Early Experience of a Randomized Controlled Trial of Radical Prostatectomy for Oligo-Metastatic Prostate Cancer: Challenges to Patient Recruitment and Effective Solutions

San Francisco, CA (UroToday.com) Standard of care for oligo-metastatic prostate cancer is currently ADT +/- chemotherapy. However, over the last several years, some retrospective studies have assessed the feasibility and safety of men undergoing radical prostatectomy in the setting of metastatic disease [1-3]. The general consensus of these studies is that radical prostatectomy is safe in highly selected patients, and decreases side-effects of locally advanced disease.

Currently, the results of a phase II, single arm trial in the US assessing radical prostatectomy in oligometastatic prostate cancer are maturing, with a phase III SWOG trial set to roll out in 2019 (personal communication, Brian Chapin, MD). Our colleagues in the UK are also running a similar trial, the Testing Radical prostatectomy in men with prostate cancer and oligoMetastases to the bone (TRoMbone) trial, a feasibility study.

Prasanna Sooriakumaran, MD, and colleagues discussed some of the initial challenges to patient recruitment and solutions implemented to overcome them.

For this trial, 50 men with synchronous oligo-metastatic prostate cancer, defined as 1-3 skeletal lesions on standard-of-care bone imaging, will be randomized 1:1 over an 18 month period to ADT +/- chemotherapy versus ADT +/- chemotherapy plus radical prostatectomy with extended pelvic lymphadenectomy. The primary outcome of the study presented today was to assess the early experience of patient recruitment and the results of a qualitative recruitment investigation incorporated into the study to understand issues and implement proposed solutions.

During the first two months of the study open at three sites, no patients were recruited. The initial qualitative recruitment investigation at that point in time demonstrated that: 

  • Surgeons and oncologists showed lack of equipoise during consultations
  • Networks were poorly configured to identify eligible patients
  • Increasing use of chemotherapy resulted in patients missing their eligibility window
  • Inconsistent use of imaging technologies meant clinicians were unclear as to patient eligibility.
Based on these findings, several potential solutions were determined:

  • Equipoise training for patient consultations
  • Re-configuring oncologist-surgeon referral pathways
  • Amending the protocol such that patients within 12 monhts of starting systemic therapy are eligible
  • Clarifying the definition of oligo-metastatic disease per imaging modality 
Most recently, TRoMbone is 50% through its recruitment period (month 9 of 18) and, as a result of the above solutions being implemented, has reached 36% of its target recruitment (18/50 men). At current rates, TRoMbone is projected to reach 60% recruitment (30/50 men) by the two-thirds stage (12 months), 70% recruitment (35/50 men) by the three-quarters stage (13.5 months), and 100% recruitment (50/50 men) by the trial recruitment end date (18 month). 

These types of qualitative analyses are important to publish and discuss within academic settings. Particularly with regards to trials that may have anticipated difficult trial enrolment, qualitative recruitment investigation appears to improve subsequent recruitment. Sooriakumaran and colleagues concluded that initial poor recruitment was investigated qualitatively and several challenges identified. With solutions implemented, recruitment has markedly increased such that successful target accrual is expected. 


References:
1. Satkunasivam R, Kim AE, Desai M, et al. Radical prostatectomy or external beam radiatiotherapy vs no local therapy for survival benefit in metastatic prostate cancer: A SEER-Medicare analysis. J Urol 2015;194(2):378-385.
2. Gratzke C, Engel J, Stief CG. Role of radical prostatectomy in metastatic prostate cancer: Data from the Munich Cancer Registry. Eur Urol 2014;66(3):602-603.
3. Heidenreich A, Pfister D, Porres D. Cytoreductive radical prostatectomy in patients with prostate cancer and low volume skeletal metastases: Results of a feasibility and case-control study. J Urol 2015;193(3):832-838.


Presented by: Prasanna Sooriakumaran, MD, Ph.D. FRCSUrol FEBU, University College London Hospital
Co-Authors: Prabhakar Rajan, Ashwin Sridhar, Pramit Khetrapal, London, United Kingdom, Christopher Eden, Surrey, United Kingdom, Freddie Hamdy, Oxford, United Kingdom, John Kelly, Senthil Nathan, London, United Kingdom, Caroline Wilson, Bristol, United Kingdom

Written by:  Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA