Trial Casts Shadow on Photodynamic Surgery for Bladder Cancer

MILAN — Photodynamic diagnosis-guided transurethral resection of bladder tumors did not reduce recurrence rates of non–muscle-invasive bladder cancer (NMIBC) in the longer term compared with standard white light cystoscopy, according to a recent randomized trial conducted in the UK.

An economic analysis also found that the photodynamic approach was costlier.

In a real-world setting comparing white light and photodynamic diagnosis for primary, intermediate to high-risk NMIBC, the trial suggests “no difference in recurrence at 3 years,” Rakesh Heer, PhD, professor of urology at Newcastle University, Newcastle upon Tyne, United Kingdom, said in an oral presentation at the European Association of Urology (EAU) Congress. Results of the trial were also published in NEJM Evidence last September.

For those of you who use the photodynamic diagnosis-guided procedure in this setting, “Are you still going to”? Heer asked audience members.

Overall, as many as 40% of NMIBCs recur after transurethral bladder resection of tumor (TURBT), likely the result of incomplete excision of malignant tissue. Evidence suggests that photodynamic diagnosis-guided resection offers improved diagnostic accuracy over white light cystoscopy, increasing the likelihood of complete resection and reducing the risk of recurrence. However, the evidence surrounding long-term efficacy and cost-effectiveness remains limited, Heer said.

To determine whether photodynamic diagnosis-guided TURBT offers superior recurrence-free survival for patients with NMIBC, Heer and colleagues conducted the pragmatic PHOTO trial, an open-label, parallel-group, randomized trial at 22 hospitals in the UK.

The authors recruited patients with a suspected first diagnosis of NMIBC who were at intermediate or high risk for recurrence based on routine visual assessment prior to TURBT. Overall, 209 were randomly assigned to photodynamic diagnosis-guided TURBT (“PDD group”) and 217 to white light-guided TURBT (“WL group”). 

Recurrences occurred in 86 patients in the PDD group and 84 patients in the WL group (hazard ratio [HR], 0.94; P = .7). The 3-year recurrence rates were similar — 57.8% in the PDD group and 61.6% in the WL group (absolute difference, 3.8 percentage points).

Rates of adverse events were under 2% and similar between the groups, with no significant differences in health-related quality of life.

Overall, the photodynamic option cost £876 ($1057) more than white light-guided option “with no evidence of a difference in quality-adjusted life years,” Heer and colleagues noted.

Invited discussant Morgan Rouprêt, MD, PhD, from Pitié-Salpêtrière Hospital in Paris, expressed skepticism about the study findings, given previous trials demonstrating strong evidence for the benefits of photodynamic diagnosis.

After acknowledging financial ties to Photocure, manufacturer of a contrast agent used in photodynamic diagnosis, Rouprêt suggested that the PHOTO trial was underpowered, noting that across 22 centers in the UK, there were only a median of 19 patients per center.

He also pointed to the learning curve required for surgical procedures, noting “operator experience and equipment are fundamental to achieving good results.”

In a rebuttal, Heer explained that the trial had a pragmatic design and was conducted in a real-world setting.

“Efficacy studies have tight controls, which don’t apply to routine practice on the whole. This is why we see many things that fail,” Heer said. “Statistically speaking, the study is still appropriately powered. It gives a real indication of the effect size, and it just does not exist.”

Heer added that “as urologists we just have to ask ourselves, if we get presented with evidence we don’t like, should we be looking at ourselves, or should we be shooting down the evidence, which appears to be the case today?”

The PHOTO trial was funded by the UK National Institute for Health and Care Research Health Technology Assessment program. Heer reports no relevant financial relationships. Disclosures for the other co-authors can be found here. Rouprêt reported a consultant and advisory role for Photocure and other companies.

European Association of Urology Annual Congress (EAU 2023). Presented March 11, 2023.

NEJM Evidence. Published September 2, 2022. Full text

Neil Osterweil, an award-winning medical journalist, is a long-standing and frequent contributor to Medscape.

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