A Randomized Trial of PHOTOdynamic Surgery in Non-Muscle-Invasive Bladder Cancer

Rakesh Heer; Rebecca Lewis; Thenmalar Vadiveloo; Ge Yu; Paramananthan Mariappan; Joanne Cresswell; John McGrath; Ghulam Nabi; Hugh Mostafid; Henry Lazarowicz; John Kelly; Anne Duncan; Steven Penegar; Matt Breckons; Laura Wilson; Emma Clark; Andy Feber; Giovany Orozco-Leal; Zafer Tandogdu; Ernest Taylor; James N'Dow; John Norrie; Craig Ramsay; Stephen Rice; Luke Vale; Graeme MacLennan; Emma Hall

doi:10.1056/EVIDoa2200092

A Randomized Trial of PHOTOdynamic Surgery in Non-Muscle-Invasive Bladder Cancer

Rakesh Heer, Rebecca Lewis, Thenmalar Vadiveloo, Ge Yu, Paramananthan Mariappan, Joanne Cresswell, John McGrath, Ghulam Nabi, Hugh Mostafid, Henry Lazarowicz, John Kelly, Anne Duncan, Steven Penegar, Matt Breckons, Laura Wilson, Emma Clark, Andy Feber, Giovany Orozco-Leal, Zafer Tandogdu, Ernest TaylorJames N'Dow, John Norrie, Craig Ramsay, Stephen Rice, Luke Vale, Graeme MacLennan, Emma Hall

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND

Recurrence of non–muscle-invasive bladder cancer (NMIBC) is common after transurethral resection of bladder tumor (TURBT). Photodynamic diagnosis (PDD) provides better diagnostic accuracy and more complete tumor resection and may reduce recurrence. However, there is limited evidence on the longer-term clinical effectiveness and cost-effectiveness of PDD-guided resection.

METHODS

In this pragmatic, open-label, parallel-group randomized trial conducted in 22 U.K. National Health Service hospitals, we recruited participants with a suspected first diagnosis of NMIBC at intermediate or high risk for recurrence on the basis of routine visual assessment before being listed for TURBT. Participants were assigned (1:1) to PDD-guided TURBT or to standard white light (WL)–guided TURBT. The primary clinical outcome was time to recurrence at 3 years of follow-up, analyzed by modified intention to treat.

RESULTS

A total of 538 participants were enrolled (269 in each group), and 112 participants without histologic confirmation of NMIBC or who had had cystectomy were excluded. After 44 months’ median follow-up, 86 of 209 in the PDD group and 84 of 217 in the WL group had recurrences. The hazard ratio for recurrence was 0.94 (95% confidence interval [CI], 0.69 to 1.28; P=0.70). Three-year recurrence-free rates were 57.8% (95% CI, 50.7 to 64.2) and 61.6% (95% CI, 54.7 to 67.8) in the PDD and WL groups, respectively, with an absolute difference of −3.8 percentage points (95% CI, −13.37 to 5.59) favoring PDD. Adverse events occurred in less than 2% of participants, and rates were similar in both groups, as was health-related quality of life. PDD-guided TURBT was £876 (95% CI, −766 to 2518; P=0.591) more costly than WL-guided TURBT over a 3-year follow-up, with no evidence of a difference in quality-adjusted life years (−0.007; 95% CI, −0.133 to 0.119; P=0.444).

CONCLUSIONS

PDD-guided TURBT did not reduce recurrence rates, nor was it cost-effective compared with WL at 3 years. (Funded by the National Institute for Health and Care Research Health Technology Assessment program; ISRCTN number, ISRCTN84013636.)

Original language	English
Article number	EVIDoa2200092
Number of pages	10
Journal	NEJM evidence
Volume	1
Issue number	10
DOIs	https://doi.org/10.1056/EVIDoa2200092
Publication status	Published - Oct 2022

Bibliographical note

Sponsored by The Newcastle upon Tyne Hospitals NHS Foundation Trust and coordinated by the Clinical Trials and Statistics Unit at The Institute of Cancer Research. Data management and statistical analyses were conducted by the Centre for Healthcare Randomised Trials at the University of Aberdeen. Cost-effectiveness analysis was conducted by the Health Economics Group at Newcastle University. This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment program and will be published in full in Health Technology Assessment Journal. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. See the NIHR Journals Library website (https://www.journalslibrary.nihr.ac.uk/hta/#/) for further project information.

Data Availability Statement

A data sharing statement provided by the authors is available with the full text of this article.

Keywords

Humans
Photosensitizing Agents
Aminolevulinic Acid
Non-Muscle Invasive Bladder Neoplasms
Urinary Bladder Neoplasms/diagnosis
Urologic Surgical Procedures

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1056/EVIDoa2200092Licence: Unspecified

Cite this

Heer, R., Lewis, R., Vadiveloo, T., Yu, G., Mariappan, P., Cresswell, J., McGrath, J., Nabi, G., Mostafid, H., Lazarowicz, H., Kelly, J., Duncan, A., Penegar, S., Breckons, M., Wilson, L., Clark, E., Feber, A., Orozco-Leal, G., Tandogdu, Z., ... Hall, E. (2022). A Randomized Trial of PHOTOdynamic Surgery in Non-Muscle-Invasive Bladder Cancer. NEJM evidence, 1(10), Article EVIDoa2200092. https://doi.org/10.1056/EVIDoa2200092

Heer, R, Lewis, R, Vadiveloo, T, Yu, G, Mariappan, P, Cresswell, J, McGrath, J, Nabi, G, Mostafid, H, Lazarowicz, H, Kelly, J, Duncan, A, Penegar, S, Breckons, M, Wilson, L, Clark, E, Feber, A, Orozco-Leal, G, Tandogdu, Z, Taylor, E, N'Dow, J, Norrie, J, Ramsay, C, Rice, S, Vale, L, MacLennan, G & Hall, E 2022, 'A Randomized Trial of PHOTOdynamic Surgery in Non-Muscle-Invasive Bladder Cancer', NEJM evidence, vol. 1, no. 10, EVIDoa2200092. https://doi.org/10.1056/EVIDoa2200092

@article{66a131f448a94388b95bec218d291fc5,

title = "A Randomized Trial of PHOTOdynamic Surgery in Non-Muscle-Invasive Bladder Cancer",

abstract = "BACKGROUNDRecurrence of non–muscle-invasive bladder cancer (NMIBC) is common after transurethral resection of bladder tumor (TURBT). Photodynamic diagnosis (PDD) provides better diagnostic accuracy and more complete tumor resection and may reduce recurrence. However, there is limited evidence on the longer-term clinical effectiveness and cost-effectiveness of PDD-guided resection.METHODSIn this pragmatic, open-label, parallel-group randomized trial conducted in 22 U.K. National Health Service hospitals, we recruited participants with a suspected first diagnosis of NMIBC at intermediate or high risk for recurrence on the basis of routine visual assessment before being listed for TURBT. Participants were assigned (1:1) to PDD-guided TURBT or to standard white light (WL)–guided TURBT. The primary clinical outcome was time to recurrence at 3 years of follow-up, analyzed by modified intention to treat.RESULTSA total of 538 participants were enrolled (269 in each group), and 112 participants without histologic confirmation of NMIBC or who had had cystectomy were excluded. After 44 months{\textquoteright} median follow-up, 86 of 209 in the PDD group and 84 of 217 in the WL group had recurrences. The hazard ratio for recurrence was 0.94 (95% confidence interval [CI], 0.69 to 1.28; P=0.70). Three-year recurrence-free rates were 57.8% (95% CI, 50.7 to 64.2) and 61.6% (95% CI, 54.7 to 67.8) in the PDD and WL groups, respectively, with an absolute difference of −3.8 percentage points (95% CI, −13.37 to 5.59) favoring PDD. Adverse events occurred in less than 2% of participants, and rates were similar in both groups, as was health-related quality of life. PDD-guided TURBT was £876 (95% CI, −766 to 2518; P=0.591) more costly than WL-guided TURBT over a 3-year follow-up, with no evidence of a difference in quality-adjusted life years (−0.007; 95% CI, −0.133 to 0.119; P=0.444).CONCLUSIONSPDD-guided TURBT did not reduce recurrence rates, nor was it cost-effective compared with WL at 3 years. (Funded by the National Institute for Health and Care Research Health Technology Assessment program; ISRCTN number, ISRCTN84013636.)",

keywords = "Humans, Photosensitizing Agents, Aminolevulinic Acid, Non-Muscle Invasive Bladder Neoplasms, Urinary Bladder Neoplasms/diagnosis, Urologic Surgical Procedures",

author = "Rakesh Heer and Rebecca Lewis and Thenmalar Vadiveloo and Ge Yu and Paramananthan Mariappan and Joanne Cresswell and John McGrath and Ghulam Nabi and Hugh Mostafid and Henry Lazarowicz and John Kelly and Anne Duncan and Steven Penegar and Matt Breckons and Laura Wilson and Emma Clark and Andy Feber and Giovany Orozco-Leal and Zafer Tandogdu and Ernest Taylor and James N'Dow and John Norrie and Craig Ramsay and Stephen Rice and Luke Vale and Graeme MacLennan and Emma Hall",

note = "Sponsored by The Newcastle upon Tyne Hospitals NHS Foundation Trust and coordinated by the Clinical Trials and Statistics Unit at The Institute of Cancer Research. Data management and statistical analyses were conducted by the Centre for Healthcare Randomised Trials at the University of Aberdeen. Cost-effectiveness analysis was conducted by the Health Economics Group at Newcastle University. This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment program and will be published in full in Health Technology Assessment Journal. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. See the NIHR Journals Library website (https://www.journalslibrary.nihr.ac.uk/hta/#/) for further project information.",

year = "2022",

month = oct,

doi = "10.1056/EVIDoa2200092",

language = "English",

volume = "1",

journal = "NEJM evidence",

issn = "2766-5526",

number = "10",

}

TY - JOUR

T1 - A Randomized Trial of PHOTOdynamic Surgery in Non-Muscle-Invasive Bladder Cancer

AU - Heer, Rakesh

AU - Lewis, Rebecca

AU - Vadiveloo, Thenmalar

AU - Yu, Ge

AU - Mariappan, Paramananthan

AU - Cresswell, Joanne

AU - McGrath, John

AU - Nabi, Ghulam

AU - Mostafid, Hugh

AU - Lazarowicz, Henry

AU - Kelly, John

AU - Duncan, Anne

AU - Penegar, Steven

AU - Breckons, Matt

AU - Wilson, Laura

AU - Clark, Emma

AU - Feber, Andy

AU - Orozco-Leal, Giovany

AU - Tandogdu, Zafer

AU - Taylor, Ernest

AU - N'Dow, James

AU - Norrie, John

AU - Ramsay, Craig

AU - Rice, Stephen

AU - Vale, Luke

AU - MacLennan, Graeme

AU - Hall, Emma

N1 - Sponsored by The Newcastle upon Tyne Hospitals NHS Foundation Trust and coordinated by the Clinical Trials and Statistics Unit at The Institute of Cancer Research. Data management and statistical analyses were conducted by the Centre for Healthcare Randomised Trials at the University of Aberdeen. Cost-effectiveness analysis was conducted by the Health Economics Group at Newcastle University. This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment program and will be published in full in Health Technology Assessment Journal. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. See the NIHR Journals Library website (https://www.journalslibrary.nihr.ac.uk/hta/#/) for further project information.

PY - 2022/10

Y1 - 2022/10

N2 - BACKGROUNDRecurrence of non–muscle-invasive bladder cancer (NMIBC) is common after transurethral resection of bladder tumor (TURBT). Photodynamic diagnosis (PDD) provides better diagnostic accuracy and more complete tumor resection and may reduce recurrence. However, there is limited evidence on the longer-term clinical effectiveness and cost-effectiveness of PDD-guided resection.METHODSIn this pragmatic, open-label, parallel-group randomized trial conducted in 22 U.K. National Health Service hospitals, we recruited participants with a suspected first diagnosis of NMIBC at intermediate or high risk for recurrence on the basis of routine visual assessment before being listed for TURBT. Participants were assigned (1:1) to PDD-guided TURBT or to standard white light (WL)–guided TURBT. The primary clinical outcome was time to recurrence at 3 years of follow-up, analyzed by modified intention to treat.RESULTSA total of 538 participants were enrolled (269 in each group), and 112 participants without histologic confirmation of NMIBC or who had had cystectomy were excluded. After 44 months’ median follow-up, 86 of 209 in the PDD group and 84 of 217 in the WL group had recurrences. The hazard ratio for recurrence was 0.94 (95% confidence interval [CI], 0.69 to 1.28; P=0.70). Three-year recurrence-free rates were 57.8% (95% CI, 50.7 to 64.2) and 61.6% (95% CI, 54.7 to 67.8) in the PDD and WL groups, respectively, with an absolute difference of −3.8 percentage points (95% CI, −13.37 to 5.59) favoring PDD. Adverse events occurred in less than 2% of participants, and rates were similar in both groups, as was health-related quality of life. PDD-guided TURBT was £876 (95% CI, −766 to 2518; P=0.591) more costly than WL-guided TURBT over a 3-year follow-up, with no evidence of a difference in quality-adjusted life years (−0.007; 95% CI, −0.133 to 0.119; P=0.444).CONCLUSIONSPDD-guided TURBT did not reduce recurrence rates, nor was it cost-effective compared with WL at 3 years. (Funded by the National Institute for Health and Care Research Health Technology Assessment program; ISRCTN number, ISRCTN84013636.)

AB - BACKGROUNDRecurrence of non–muscle-invasive bladder cancer (NMIBC) is common after transurethral resection of bladder tumor (TURBT). Photodynamic diagnosis (PDD) provides better diagnostic accuracy and more complete tumor resection and may reduce recurrence. However, there is limited evidence on the longer-term clinical effectiveness and cost-effectiveness of PDD-guided resection.METHODSIn this pragmatic, open-label, parallel-group randomized trial conducted in 22 U.K. National Health Service hospitals, we recruited participants with a suspected first diagnosis of NMIBC at intermediate or high risk for recurrence on the basis of routine visual assessment before being listed for TURBT. Participants were assigned (1:1) to PDD-guided TURBT or to standard white light (WL)–guided TURBT. The primary clinical outcome was time to recurrence at 3 years of follow-up, analyzed by modified intention to treat.RESULTSA total of 538 participants were enrolled (269 in each group), and 112 participants without histologic confirmation of NMIBC or who had had cystectomy were excluded. After 44 months’ median follow-up, 86 of 209 in the PDD group and 84 of 217 in the WL group had recurrences. The hazard ratio for recurrence was 0.94 (95% confidence interval [CI], 0.69 to 1.28; P=0.70). Three-year recurrence-free rates were 57.8% (95% CI, 50.7 to 64.2) and 61.6% (95% CI, 54.7 to 67.8) in the PDD and WL groups, respectively, with an absolute difference of −3.8 percentage points (95% CI, −13.37 to 5.59) favoring PDD. Adverse events occurred in less than 2% of participants, and rates were similar in both groups, as was health-related quality of life. PDD-guided TURBT was £876 (95% CI, −766 to 2518; P=0.591) more costly than WL-guided TURBT over a 3-year follow-up, with no evidence of a difference in quality-adjusted life years (−0.007; 95% CI, −0.133 to 0.119; P=0.444).CONCLUSIONSPDD-guided TURBT did not reduce recurrence rates, nor was it cost-effective compared with WL at 3 years. (Funded by the National Institute for Health and Care Research Health Technology Assessment program; ISRCTN number, ISRCTN84013636.)

KW - Humans

KW - Photosensitizing Agents

KW - Aminolevulinic Acid

KW - Non-Muscle Invasive Bladder Neoplasms

KW - Urinary Bladder Neoplasms/diagnosis

KW - Urologic Surgical Procedures

U2 - 10.1056/EVIDoa2200092

DO - 10.1056/EVIDoa2200092

M3 - Article

C2 - 38319866

SN - 2766-5526

VL - 1

JO - NEJM evidence

JF - NEJM evidence

IS - 10

M1 - EVIDoa2200092

ER -

A Randomized Trial of PHOTOdynamic Surgery in Non-Muscle-Invasive Bladder Cancer

Abstract

Bibliographical note

Data Availability Statement

Keywords

UN SDGs

Access to Document

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