Syed Hammad Tirmazy: Key Debate Emerging from the PROTEUS Trial in High-Risk cN1 Prostate Cancer
Syed Hammad Tirmazy/eos-uae.com

Syed Hammad Tirmazy: Key Debate Emerging from the PROTEUS Trial in High-Risk cN1 Prostate Cancer

Syed Hammad Tirmazy, EMA Cultural Committe Chairperson at Emirates Oncology Society, shared a post on LinkedIn:

“Interesting and important discussion emerging from the PROTEUS trial in high-risk/cN1 prostate cancer.

I find the comparison with STAMPEDE particularly fascinating because the two studies represent very different treatment philosophies.

STAMPEDE demonstrated excellent outcomes with a radiotherapy-based approach using pelvic RT + long-term ADT + 2 years of abiraterone, despite understandable concerns regarding toxicity and treatment duration.

PROTEUS, meanwhile, takes a surgery-based strategy with peri-operative ADT/apalutamide + radical prostatectomy + pelvic lymph node dissection (PLND), and clearly shows strong biological activity with improved pathological responses and MFS.

However, several important questions remain:

  • Does PLND control microscopic pelvic nodal disease as effectively as pelvic RT?
  • Did neoadjuvant ADT/ARPI downstage disease to the point that we lose the ability to identify who truly needed adjuvant/salvage RT?
  • Could some patients actually be undertreated in the pelvis despite intensified systemic therapy?
  • Is 1 year of systemic intensification enough when STAMPEDE used 2 years?
  • How variable was the quality and extent of RP/PLND between surgeons and centres?
  • Will PROTEUS truly improve long-term outcomes, or mainly expand acceptance of surgery in more locally advanced disease?

For me, PROTEUS is definitely positive and important, but at this stage probably more hypothesis-changing than fully practice-changing until we see mature OS data, nodal subgroup analyses, surgical quality metrics and patterns of pelvic relapse.

Curious to hear views from uro-oncology colleagues regarding management of cN1/pelvic nodal disease and whether this changes MDT decision-making in routine practice.”