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© 2023 The Authors. Société Internationale d'Urologie Journal, published by the Société Internationale d'Urologie, Canada.

SIUJ.ORG SIUJ  •  Volume 4, Number 3  •  May 2023

Key Words Competing Interests Article Information

Bladder cancer, NMIBC, blue light cystoscopy None declared. Received on November 15, 2022 
Accepted on December 24, 2022 
This article has been peer reviewed.

Soc Int Urol J. 2023;4(3):223–225

DOI: 10.48083/ANXW6767

223

PRO AND CON

Continued Use and Expansion  
of Photodynamic TURBT

Michael E. Rezaee, Max Kates

Johns Hopkins Medical Institutions, Baltimore, United States

Doubt is not a pleasant condition, but certainty is an absurd one. – Voltaire

Urology has been fraught with informing practice based on weak evidence, and when a randomized controlled trial 
comes along in our field, it should be applauded. But to applaud the completion of a trial does not mean to kneel at 
its altar. We should ask ourselves 2 questions of every clinical trial: (1) does the trial address an important question, 
and (2) was the trial designed and conducted in such a way to successfully answer the intended question. The PHOTO 
trial, which was recently published in the New England Journal of Medicine Evidence is a trial that successfully answers 
a question that is largely unimportant.

Among patients with intermediate-risk non-muscle invasive bladder cancer (NMIBC) with low rates of both carci-
noma in situ (CIS) and adjuvant Bacillus Calmette-Guérin (BCG) therapy, initial photodynamic transurethral resec-
tion of bladder tumor (TURBT) did not perform any better than traditional white-light TURBT in terms of 3-year 
disease recurrence in a large, multicenter, randomized trial[1]. As such, many urologists now wonder if photodynamic 
TURBT should be abandoned, especially given the costs associated with this technology. The answer is no. In fact, we 
favor the continued use and expansion of photodynamic TURBT in appropriate patients.

The risk for disease recurrence in intermediate-risk NMIBC ranges from 40% to 56% based on European Organ-
isation for Research and Treatment of Cancer (EORTC) estimates, while up to 75% to 80% of patients with high-risk 
disease will experience a recurrence[2]. As such, the PHOTO trial enrolled patients with suspected intermediate or 
high-risk NIMBC who were expected to have recurrences. However, study enrollment was based on tumor cysto-
scopic appearance (eg, flat velvety erythematous mucosal changes) or imaging characteristics (eg, tumor ≥ 3 cm), not 
pathology specimens. This resulted in 89 patients (16.5%) being automatically excluded from the trial due to having 
muscle-invasive bladder cancer (MIBC) or no tumor at the time of TURBT. In addition, 374 (88%) patients enrolled 
in the trial had EORTC intermediate-risk disease (46% intermediate-risk by National Institute for Health and Care 
Excellence criteria[3]), while 32 (7.5%) had high-risk disease and 18 (4.2%) could not be classified. This enrollment 
design reduced the number of potential tumor recurrences (the main study outcome) that could have been observed 
in the trial by 1) enrolling patients who would never have a recurrence, and 2) primarily enrolling patients at only 
intermediate risk for recurrence. The authors explain that the primary implication of this limitation is a reduction 
in predefined study power from 90% to around 80%. However, we believe this enrollment methodology likely also 
shifted the population of interest away from patients who would benefit from photodynamic TURBT the most.

Patients with high-risk NMIBC experience the greatest benefit from photodynamic TURBT, particularly those 
with CIS[4,5]. Photodynamic TURBT has been shown to detect 32% more high-risk tumors compared to white-light 
TURBT and 36% more CIS lesions, specifically[6]. In fact, multiple studies have demonstrated the additive benefit of 
photodynamic TURBT in detecting CIS compared with white-light TURBT[7,8]. Unfortunately, only 32 (7.5%) and  
51 (9.5%) patients enrolled in the PHOTO trial had EORTC high-risk NMIBC and CIS, respectively. Thus, the results 
of the PHOTO trial likely do not adequately represent the true potential benefit of photodynamic TURBT in high-risk 
patients, for which the technology is most appropriate for.

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Another important limitation of the PHOTO trial 
was the underutilization of adjuvant BCG, an intraves-
ical therapy known to reduce tumor recurrences and 
progression in NMIBC[9]. Only 68 (16.0%) patients in 
the final analysis cohort received induction plus mainte-
nance BCG and 35 (8.2%) received induction BCG alone. 
BCG use was particularly dismal among patients with 
high-risk disease, with only 14 patients receiving induc-
tion and 7 receiving maintenance. These utilization rates 
are concerning given the known oncological benefits of 
BCG in high-risk NMIBC[2]. Most importantly, these 
rates suggest that many patients did not receive standard 
of care for adjuvant intravesical therapy. It is therefore 
not surprising that although at 1 year there is separation 
of the recurrence-free survival curves favoring photo-
dynamic TURBT, by 3 years there was no difference. 
The fact that most patients in the trial were EORTC 
intermediate-risk NMIBC without CIS means that the 
trial is studying a population with fewer recurrences, 
lower stakes for patients and providers, and less proven 
outcomes with use of photodynamic technology. In the 
small group of patients with EORTC high-risk NMIBC, 
the fact that a small fraction was treated with standard-
of-care intravesical therapy means that the trial merely 
demonstrates that untreated high-risk NMIBC leads to 
recurrences.

A recent meta-analysis of 12 randomized trials found 
that photodynamic TURBT improved recurrence-free 
survival compared to white-light TURBT at 2 years 
of follow-up[4]. The PHOTO trial does not erase this 
prior evidence supporting the utility of photodynamic 
TURBT. Instead, it adds to a growing literature base 

Abbreviations 
BCG Bacillus Calmette-Guérin
CIS carcinoma in situ
EORTC Organisation for Research and Treatment of Cancer
NMIBC non-muscle invasive bladder cancer
TURBT transurethral resection of bladder tumor

available to urologists to continue to improve the quality 
of care delivered to patients with bladder cancer. Over-
all, NMIBC care is highly nuanced with varying disease 
trajectories, surveillance strategies, and treatment 
options. The PHOTO trial suggests that photodynamic 
TURBT may have limited utility when used at the initial 
diagnosis of patients with intermediate-risk disease, 
but there are many patients and clinical scenarios that 
other studies have shown derive benefit from photody-
namic TURBT. Our approach to the patient demands 
that we be nuanced in interpreting the trial’s findings. 
An example of this is the use of immediate postopera-
tive intravesical chemotherapy in intermediate-risk 
NMIBC. Intermediate-risk patients with an EORTC 
recurrence score ≥ 6 (e.g., multiple tumors, at least one 
≥ 3 cm) do not benefit from postoperative intravesi-
cal chemotherapy. However, those with a score < 6 can 
experience up to a 35% reduction in recurrence risk[10]. 
Despite not having any oncologic benefit in some inter-
mediate-risk patients, postoperative intravesical chemo-
therapy is commonly pursued in all intermediate-risk 
patients because the potential benefit for some patients 
outweighs the risk in most patients. If 1 in 10 or 1 in 20 
patients derives benefit from the introduction of a tech-
nology, then all it takes is a few interventions like that to 
impact a sizable portion of patients with bladder cancer. 
Because the PHOTO trial did not enroll many patients 
with CIS or high-risk NMIBC, it was not powered to 
identify these differences.

Based on the limitations of the PHOTO trial, avail-
able prior research, and the nuances of bladder cancer 
care, we support the continued use and expansion of 
photodynamic TURBT in NMIBC. This technology 
should be used in patients with high-risk NMIBC, espe-
cially those with CIS. Use in intermediate-risk disease 
is also likely justified for many patients, despite the trial 
results. Based on our experience, we also believe there 
is significant utility for this technology in restaging 
TURBTs to identify CIS, during mucosal mapping for 
partial cystectomy and trimodality therapy planning, 
and for assessing response to intravesical therapy.

224 SIUJ  •  Volume 4, Number 3  •  May 2023 SIUJ.ORG

PRO AND CON

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Continued Use and Expansion of Photodynamic TURBT

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