The position paper endorsed by the Italian Society of Urology (SIU)1 offers a comprehensive and authoritative synthesis of current evidence and expert consensus regarding the clinical use of photodynamic diagnosis (PDD) in the management of non-muscle invasive bladder cancer (NMIBC). While PDD has been widely investigated over the past two decades, with data from randomized controlled trials supporting its value in improving tumor detection and reducing recurrence, its integration into routine clinical practice has remained heterogeneous across national settings.2 The rationale behind its adoption is justified by the high bladder cancer recurrence rates despite postoperative intravesical chemotherapy, immunotherapy, or regular cystoscopy surveillance. In this context, ongoing efforts aim to identify novel diagnostic markers and imaging techniques to improve risk stratification and capture the full biological spectrum of early-stage disease.3-6 Indeed, failure to detect and adequately treat satellite lesions and/or the full extent of the primary tumor may contribute to 20-40% of recurrences.2, 7, 8 Mechanistically, PDD enhances the visualization of suspicious bladder cancer lesions, particularly carcinoma in situ (CIS), by exploiting the selective accumulation of photosensitizers in neoplastic cells and their excitation under specific wavelengths.9 Initial transurethral resection of the bladder (TURB) remains crucial for accurate risk stratification and appropriate follow-up in patients with NMIBC.10-12 In this setting, PDD may be particularly helpful during the initial TURB to avoid missing CIS or small papillary lesions that could lead to residual disease or early recurrence. The SIU panel outlines several key clinical scenarios in which PDD may add value: •papillary lesions with positive cytology (suggestive of underlying high-grade disease); •large tumors (>3 cm), which carry a 70% likelihood of harbouring high-grade features;13 •multifocal tumors or atypical macroscopic features such as sessile or solid appearance; •negative cystoscopy and imaging in the context of positive urine cytology – where PDD may replace random biopsies, given the 60% sensitivity of cytology for CIS.9 In all such cases, the use of PDD may enhance diagnostic precision and support more individualized treatment pathways. The Panel also strongly advises the use of PDD during re-TURB, unless already performed at initial resection. In the follow-up setting, PDD may be indicated in recurrent tumors with high-risk features (tumor size >3 cm, multifocality, positive cytology), in intermediate-high or high-risk NMIBC, and to assess CIS response following BCG therapy. Importantly, PDD can aid in ruling out BCG-unresponsive NMIBC – although a prior history of BCG exposure may increase false-positive rates and reduce diagnostic accuracy.14, 15 While the value of PDD is widely supported, controversy remains. A recent randomized trial reported no significant benefit in recurrence-free survival (RR 0.94, P=0.70) or quality-adjusted life years, while incurring higher costs for PDD-guided TURB.2 In addition, potential drawbacks – such as hypotension, nausea, phototoxicity, and false positives due to inflammation or metaplasia - must be considered. Notably, false-positive findings are more common at the bladder neck, trigone, and ureteral orifices.16 Thus, while PDD is undoubtedly a valuable tool for improving bladder cancer detection, its use should be thoughtfully balanced with system-level considerations of cost-effectiveness and healthcare resource allocation. Ultimately, this position paper by the SIU makes a significant contribution to the literature. It provides a clear, evidence-informed roadmap for Italian clinicians, reinforces the role of PDD as an adjunct to optimize NMIBC management, and may serve as a reference for other national urological societies seeking to integrate advanced diagnostic technologies into everyday clinical pathways.
Comment on: "The current role of photodynamic diagnosis (PDD) in the management of non-muscle invasive bladder cancer: the Italian Society of Urology (SIU) Position Paper"
Lasorsa, Francesco;Ditonno, Pasquale;Lucarelli, Giuseppe
2025-01-01
Abstract
The position paper endorsed by the Italian Society of Urology (SIU)1 offers a comprehensive and authoritative synthesis of current evidence and expert consensus regarding the clinical use of photodynamic diagnosis (PDD) in the management of non-muscle invasive bladder cancer (NMIBC). While PDD has been widely investigated over the past two decades, with data from randomized controlled trials supporting its value in improving tumor detection and reducing recurrence, its integration into routine clinical practice has remained heterogeneous across national settings.2 The rationale behind its adoption is justified by the high bladder cancer recurrence rates despite postoperative intravesical chemotherapy, immunotherapy, or regular cystoscopy surveillance. In this context, ongoing efforts aim to identify novel diagnostic markers and imaging techniques to improve risk stratification and capture the full biological spectrum of early-stage disease.3-6 Indeed, failure to detect and adequately treat satellite lesions and/or the full extent of the primary tumor may contribute to 20-40% of recurrences.2, 7, 8 Mechanistically, PDD enhances the visualization of suspicious bladder cancer lesions, particularly carcinoma in situ (CIS), by exploiting the selective accumulation of photosensitizers in neoplastic cells and their excitation under specific wavelengths.9 Initial transurethral resection of the bladder (TURB) remains crucial for accurate risk stratification and appropriate follow-up in patients with NMIBC.10-12 In this setting, PDD may be particularly helpful during the initial TURB to avoid missing CIS or small papillary lesions that could lead to residual disease or early recurrence. The SIU panel outlines several key clinical scenarios in which PDD may add value: •papillary lesions with positive cytology (suggestive of underlying high-grade disease); •large tumors (>3 cm), which carry a 70% likelihood of harbouring high-grade features;13 •multifocal tumors or atypical macroscopic features such as sessile or solid appearance; •negative cystoscopy and imaging in the context of positive urine cytology – where PDD may replace random biopsies, given the 60% sensitivity of cytology for CIS.9 In all such cases, the use of PDD may enhance diagnostic precision and support more individualized treatment pathways. The Panel also strongly advises the use of PDD during re-TURB, unless already performed at initial resection. In the follow-up setting, PDD may be indicated in recurrent tumors with high-risk features (tumor size >3 cm, multifocality, positive cytology), in intermediate-high or high-risk NMIBC, and to assess CIS response following BCG therapy. Importantly, PDD can aid in ruling out BCG-unresponsive NMIBC – although a prior history of BCG exposure may increase false-positive rates and reduce diagnostic accuracy.14, 15 While the value of PDD is widely supported, controversy remains. A recent randomized trial reported no significant benefit in recurrence-free survival (RR 0.94, P=0.70) or quality-adjusted life years, while incurring higher costs for PDD-guided TURB.2 In addition, potential drawbacks – such as hypotension, nausea, phototoxicity, and false positives due to inflammation or metaplasia - must be considered. Notably, false-positive findings are more common at the bladder neck, trigone, and ureteral orifices.16 Thus, while PDD is undoubtedly a valuable tool for improving bladder cancer detection, its use should be thoughtfully balanced with system-level considerations of cost-effectiveness and healthcare resource allocation. Ultimately, this position paper by the SIU makes a significant contribution to the literature. It provides a clear, evidence-informed roadmap for Italian clinicians, reinforces the role of PDD as an adjunct to optimize NMIBC management, and may serve as a reference for other national urological societies seeking to integrate advanced diagnostic technologies into everyday clinical pathways.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
