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

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

Key Words Competing Interests Article Information

Targeted biopsy, prostate cancer, 
multiparametric MRI, fusion biopsy

None declared. Received on October 15, 2022 
Accepted on October 22, 2022 
This article has been peer reviewed.

Soc Int Urol J. 2023;4(3):226–227

DOI: 10.48083/LTML9783

226

PRO AND CON

The End of Photodynamic Surgery 
for Bladder Cancer Has Arrived

Benjamin Davies

Department of Urology, University of Pittsburgh Medical Center Health System, Pittsburgh, United States

The PHOTO study was a real-world—or “pragmatic” in the proper diction of the UK investigators—prospective 
randomized controlled trial (RCT) to evaluate bladder cancer recurrence rates with over 3 years of follow-up. This 
is the longest RCT performed on this technology published. It was extraordinarily vigorous—even for the high 
standards of any RCT. There was central randomization with concealed allocation, blinding of personnel and 
outcome assessors, low rates of attrition, and a pre-published analytics plan. Critically, the funding was governmental 
not pharmaceutical. The control arm and study arm were equally balanced. This study did allow for the appropriate 
use of postoperative intravesical therapy and adjuvant treatment, all of which were equally balanced in both arms. A 
real-world trial has shown—without any doubt at all—that the use of photodynamic diagnosis (PDD) for the express 
purpose of preventing recurrence after the initial diagnosis of bladder cancer is unhelpful.

This negative result should not be a surprise. Urologists only have to recall the original randomized trial that 
formed the basis for the approval of PDD at the FDA to remind themselves this technology was always borderline[1]. 
In the final phase 3 trial, PDD met only one of its prespecified endpoints and failed to achieve superiority in compar-
ison for follow-up recurrence rates. The proportion of the PDD group patients detected (16%) did exceed the prespec-
ified 10% threshold, however. Supporting documentation at the time (Study 304), which did randomize to white light 
versus PDD, did not show a reduction in recurrence. The FDA advisory committee voted 9 to 8 in favor of sufficient 
risk to benefit for using PDD. A “slow-clap” approval if there ever was one.

After the PHOTO study has been disseminated, studied, and dissected—we should see an international steep 
decline in the pro forma use of PDD for the purposes of preventing bladder cancer recurrence. Why? It doesn’t work. 
In countries such as the United States where pharmaceutical representatives foot the bill for the lion’s share of post-
graduate education, PDD use will likely plod along buttressed by conflicted experts. In the United Kingdom, home of 
the PHOTO study and where general adherence to evidence-based medicine can happen, PDD use will peter out and 
be used in select cases only.

Physicians do not consider one study to inform their practice. Instead, physicians should consider all the high-
value studies packaged into a meta-analysis. Urologists should therefore appreciate the work of Maisch et al.[2], who 
in 2021 (prior to PHOTO) performed a rigorous systematic review of all studies on PDD and recurrence rates. Those 
authors downgraded the certainty of evidence by two levels according to the Grading of Recommendations Assess-
ment, Development and Evaluation (GRADE) framework. They found there was significant unexplained heteroge-
neity in the data on PDD and recurrence. If the PHOTO trial was added, according to Heer et al. [3], and the analysis 
was restricted to only robust trials with a priori protocols—the entirety of all PDD RCT studies would result in a 
nonsignificant result. PDD just cannot get a break.

There are many reports in the literature that PDD provides superior diagnostic capabilities in the setting of carci-
noma in situ (CIS), a point the PDD lobbyists will surely cling to. Those reports—while numerous and retrospective—
have heterogeneous patient characteristics and study design[4]. Now, we have the clear cover of a modern real-world 

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RCT, which was enriched with 12.9% of the PDD group 
versus 11.1% of the WL group, with CIS, showing no 
clear difference in recurrence rates.

Modern high-definition cystoscopy, unavailable in 
the original RCT but available to all currently, is one 
obvious reason PDD crumbled in this non-pharmaceu-
tically sponsored PHOTO trial. The real-world addition 
of intravesical therapy and re-resection of tumors also 

undoubtedly contributed. All told, payors and national 
health services should restrict this expensive technol-
ogy immediately. Thomas Jefferson was fond of saying,  
“He who knows nothing is closer to the truth than he 
whose mind is filled with falsehoods and errors.” Time 
to shed the errors and realize the truth: PDD is past its 
prime and high-definition optics has come to the fore.

References

1. Grossman HB, Stenzl A, Fradet Y, Mynderse L A, Kriegmair M, 
Witjes JA, et al. Long-term decrease in bladder cancer recurrence 
with hexaminolevulinate enabled fluorescence cystoscopy.  
J Urol.2012;188(1):58–62. doi: 10.1016/j.juro.2012.03.007. PMID: 
22583635; PMCID: PMC3372634.

2. Maisch P, Koziarz A, Vajgrt J, Narayan V, Kim MH, Dahm P. Blue 
versus white light for transurethral resection of non-muscle invasive 
bladder cancer. Cochrane Database Syst Rev.2021;12(12):CD013776. 
doi: 10.1002/14651858.CD013776.pub2. PMID: 34850382; PMCID: 
PMC8632646.

3. Heer R, Lewis R, Vadiveloo T, Yu G, Mariappan P, Cresswell J, et al.  
A randomized trial of PHOTOdynamic surgery in non–muscle-invasive 
bladder cancer. NEJM Evid.2022;1(10). doi: 10.1056/EVIDoa2200092.

4. Veeratterapillay R, Gravestock P, Nambiar A, Gupta A, Aboumarzouk 
O, Rai B, et al. Time to turn on the blue lights: a systematic review 
and meta-analysis of photodynamic diagnosis for bladder cancer. Eur 
Urol Open Sci.2021;31:17–27. doi: 10.1016/j.euros.2021.06.011. PMID: 
34467237; PMCID: PMC8385287.b renal cell carcinomas in patients 
with comorbidities. Jpn J Radiol. 2021;39(12):1213–1222. doi: 10.1007/
s11604-021-01168-8. PMID: 34228240.

227SIUJ.ORG SIUJ  •  Volume 4, Number 3  •  May 2023

The End of Photodynamic Surgery for Bladder Cancer Has Arrived

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