We read with great interest the article by Demirbilek et al [1] on their external validation of nomograms for predicting pelvic lymph-node metastases and assessment of the added value of the prostate-specific membrane antigen (PSMA) positron emission tomography (PET)-based PRIMARY score. Their findings provide meaningful contributions to the ongoing refinement of preoperative lymph-node staging in prostate cancer.
From a methodological perspective, we commend the authors for their rigorous inclusion criteria, standardized PSMA PET protocol, and detailed pathological evaluation by experienced uropathologists. Their confirmation of the superior diagnostic performance of the Amsterdam-Brisbane-Sydney nomogram (area under the receiver operating characteristic curve [AUC] 0.862) aligns with emerging evidence supporting PSMA-informed staging tools in contemporary clinical practice [2].
Nonetheless, several methodological considerations merit discussion. The incorporation of PSMA PET findings into clinical decision-making may introduce verification bias: as patients with positive PET findings are more likely to undergo extensive lymph-node dissection, the likelihood of identifying pN1 disease in this group inherently increases [3]. The marginal improvement in AUC after adding the PRIMARY score (0.870 vs 0.862) showed overlapping confidence intervals, which emphasizes the need for larger prospective trials to confirm true clinical significance beyond statistical refinement.
From a translational standpoint, the study highlights the biological relevance of intraprostatic PSMA uptake patterns. Higher PRIMARY scores for pN1 cases are consistent with prior evidence linking PSMA expression to tumor aggressiveness, alterations in androgen-receptor signaling genes, stromal-epithelial interactions, and hypoxia-driven PSMA upregulation [4], [5]. Such biological insights support the integration of intraprostatic PSMA metrics (maximum and mean standardized uptake values, PRIMARY score) into decision-making tools for a more molecularly grounded approach to nodal staging.
In conclusion, the study by Demirbilek et al [1] represents an important contribution to the evolving landscape of PSMA-based prostate cancer staging. We encourage future prospective multicenter studies with centralized imaging review to better define the clinical impact of PRIMARY-integrated nomograms on surgical decision-making and long-term oncological outcomes.
Conflict of interest: The authors have nothing to disclose.
References
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