Retrospective data have shown that patients scheduled for radical prostatectomy who are staged with PSMA PET/CT have less risk of recurrence (Sweere et al. 2025). This suggests a significant improvement in patient selection, most likely because conventional imaging fails to identify patients who should have been recommended systemic therapy. PSMA PET/CT has now made its way into international guidelines, and the nuclear physician discipline is fully integrated in all aspects of urological oncology.
Introduction of novel and more sensitive diagnostic tests poses several common dilemmas in clinical practice; stage migration being the most challenging factor, but also the fact that most existing research evidence is based on conventional tests. Publications supporting the use of PSMA PET/CT are rapidly increasing, and the initial skepticism that existed in the early phases of its application is diminishing. However, many questions remain unanswered, and one of the most controversial topics is the management of the regional lymph nodes. Even before the introduction of molecular imaging, no clear evidence has been provided to guide the decision whether to perform pelvic lymph node dissection (PLND) or not. It has been concluded that there is no evidence supporting a therapeutic benefit, even though no robust randomized studies have been conducted to date. PLND was previously recommended to gain prognostic information. Now that PSMA PET/CT provides a more accurate staging of the lymph nodes, it is unclear what role the PLND plays for the patient and the surgeon.
Two main questions arise in this context:
- If the PSMA PET/CT is negative for nodal affection, can we safely avoid PLND?
- If the PSMA PET/CT indicates positive regional lymph nodes, can PLND have a therapeutic role?
In the prePSMA trial, patients scheduled for radical prostatectomy are staged with PSMA PET/CT and randomized to extended PLND (ePLND) or no ePLND if the imaging is negative for regional lymph nodes (Figure 1). If we were to find proper answers to both aforementioned questions, we should have randomized patients with positive regional lymph nodes in the same fashion. This would, however, be considered ethically questionable. Leaving radiologically proven disease untreated could put patients at risk of worse outcomes. We anticipate that some patients in the PSMA PET/CT-negative cohort will have micrometastatic disease, potentially representing the subgroup in which a treatment effect can be seen, should it exist.
Figure 1: Trial schema. PSMA = prostate-specific membrane antigen; PET = positron emission tomography; CT = computed tomography; RALP = robot-assisted radical prostatectomy; ePLND = extended pelvic lymph node dissection; mi = molecular imaging.
Written by:
- Lars F. Qvigstad, MD, Department of Cancer Surgery, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
- Viktor Berge, MD, PhD, Department of Cancer Surgery, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway