Risks and Benefits of Adjuvant Radiotherapy After Inguinal Lymphadenectomy in Node-positive Penile Cancer

A Systematic Review by the European Association of Urology Penile Cancer Guidelines Panel

Richard Robinson, Lorenzo Marconi, Ekelechi MacPepple, Oliver W. Hakenberg, Nick Watkin, Yuhong Yuan, Thomas Lam, Steven MacLennan, Temitope E. Adewuyi, Alberto Coscione, Suks S. Minhas, Eva M. Compérat, Andrea Necchi

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Abstract

Context

Management of men with penile squamous cell carcinoma (PSCC) who have high-risk features following radical inguinal lymphadenectomy (ILND) remains controversial. European Association of Urology guidelines state that adjuvant inguinal radiotherapy (AIRT) is “not generally recommended”. Despite this, many centres continue to offer AIRT to a subset of men.

Objective

To undertake a systematic review of the evidence on AIRT in node-positive men with PSCC.

Evidence acquisition

A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with no language or date restriction. Inclusion criteria were men with PSCC, pathologically staged inguinal node positive after ILND. The intervention included ILND with AIRT compared with ILND alone. Primary outcomes were relapse-free survival and toxicity. Risk of bias assessment was undertaken.

Evidence synthesis

A total of 913 abstracts were identified and screened independently by two reviewers. Seven studies were eligible for inclusion: six full-text manuscripts and one conference abstract. All were retrospective series and at a high risk of bias. The selected studies included 1605 men. Indications for AIRT varied but were typically involvement of two or more inguinal nodes or extranodal extension. Regional recurrence rate following AIRT was reported at 10–91.7%. Only one study reported on toxicity. Two studies compared recurrence and survival between men who received and who did not receive AIRT, with no significant difference (p > 0.05).

Conclusions

The evidence indicates that men treated with AIRT do not gain benefit with respect to relapse or survival. Uncertainty remains due to the retrospective nature and high risks of bias across the evidence. Given the lack of evidence supporting AIRT, it cannot be recommended for routine practice.

Patient summary

Men with penile cancer who have involvement of the inguinal lymph nodes are at a high risk of cancer recurrence and death. We reviewed the literature to see if radiation treatment after removal of the nodes provided benefit. We did not find any good-quality evidence supporting this treatment, and hence it cannot be recommended.

Original languageEnglish
Pages (from-to)76-83
Number of pages8
JournalEuropean Urology
Volume74
Issue number1
Early online date24 Apr 2018
DOIs
Publication statusPublished - Jul 2018

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Penile Neoplasms
Adjuvant Radiotherapy
Groin
Lymph Node Excision
Guidelines
Recurrence
Squamous Cell Carcinoma
Survival
Manuscripts

Keywords

  • penile cancer
  • adjuvant radiotherapy
  • lymph nodes

Cite this

Risks and Benefits of Adjuvant Radiotherapy After Inguinal Lymphadenectomy in Node-positive Penile Cancer : A Systematic Review by the European Association of Urology Penile Cancer Guidelines Panel. / Robinson, Richard; Marconi, Lorenzo; MacPepple, Ekelechi; Hakenberg, Oliver W.; Watkin, Nick; Yuan, Yuhong; Lam, Thomas; MacLennan, Steven; Adewuyi, Temitope E.; Coscione, Alberto; Minhas, Suks S.; Compérat, Eva M.; Necchi, Andrea.

In: European Urology, Vol. 74, No. 1, 07.2018, p. 76-83.

Research output: Contribution to journalArticle

Robinson, Richard ; Marconi, Lorenzo ; MacPepple, Ekelechi ; Hakenberg, Oliver W. ; Watkin, Nick ; Yuan, Yuhong ; Lam, Thomas ; MacLennan, Steven ; Adewuyi, Temitope E. ; Coscione, Alberto ; Minhas, Suks S. ; Compérat, Eva M. ; Necchi, Andrea. / Risks and Benefits of Adjuvant Radiotherapy After Inguinal Lymphadenectomy in Node-positive Penile Cancer : A Systematic Review by the European Association of Urology Penile Cancer Guidelines Panel. In: European Urology. 2018 ; Vol. 74, No. 1. pp. 76-83.
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title = "Risks and Benefits of Adjuvant Radiotherapy After Inguinal Lymphadenectomy in Node-positive Penile Cancer: A Systematic Review by the European Association of Urology Penile Cancer Guidelines Panel",
abstract = "ContextManagement of men with penile squamous cell carcinoma (PSCC) who have high-risk features following radical inguinal lymphadenectomy (ILND) remains controversial. European Association of Urology guidelines state that adjuvant inguinal radiotherapy (AIRT) is “not generally recommended”. Despite this, many centres continue to offer AIRT to a subset of men.ObjectiveTo undertake a systematic review of the evidence on AIRT in node-positive men with PSCC.Evidence acquisitionA systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with no language or date restriction. Inclusion criteria were men with PSCC, pathologically staged inguinal node positive after ILND. The intervention included ILND with AIRT compared with ILND alone. Primary outcomes were relapse-free survival and toxicity. Risk of bias assessment was undertaken.Evidence synthesisA total of 913 abstracts were identified and screened independently by two reviewers. Seven studies were eligible for inclusion: six full-text manuscripts and one conference abstract. All were retrospective series and at a high risk of bias. The selected studies included 1605 men. Indications for AIRT varied but were typically involvement of two or more inguinal nodes or extranodal extension. Regional recurrence rate following AIRT was reported at 10–91.7{\%}. Only one study reported on toxicity. Two studies compared recurrence and survival between men who received and who did not receive AIRT, with no significant difference (p > 0.05).ConclusionsThe evidence indicates that men treated with AIRT do not gain benefit with respect to relapse or survival. Uncertainty remains due to the retrospective nature and high risks of bias across the evidence. Given the lack of evidence supporting AIRT, it cannot be recommended for routine practice.Patient summaryMen with penile cancer who have involvement of the inguinal lymph nodes are at a high risk of cancer recurrence and death. We reviewed the literature to see if radiation treatment after removal of the nodes provided benefit. We did not find any good-quality evidence supporting this treatment, and hence it cannot be recommended.",
keywords = "penile cancer, adjuvant radiotherapy, lymph nodes",
author = "Richard Robinson and Lorenzo Marconi and Ekelechi MacPepple and Hakenberg, {Oliver W.} and Nick Watkin and Yuhong Yuan and Thomas Lam and Steven MacLennan and Adewuyi, {Temitope E.} and Alberto Coscione and Minhas, {Suks S.} and Comp{\'e}rat, {Eva M.} and Andrea Necchi",
note = "Richard Robinson certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Dr. Thomas Lam is a company consultant for and has received company speaker honoraria from Pfizer, GSK, Astellas, and Ipsen. Mr. Suks S. Minhas receives company speaker honorarium for Lilly and has received a fellowship/medical travel grant from American Medical systems Fellowship. Dr. Andrea Necchi is a company consultant for and has received company speaker honoraria from Bayer and Astra Zeneca, and has received a fellowship/medical travel grant from Pierre Fabre; he has been involved with trial participation for Roche, Merck Sharp & Dohme, BMS, and Novartis, as well as receiving grants/research supports from GlaxoSmithKline and Millenium. Oliver Hakenberg, Nick Watkin, Richard Robinson, Yuhong Yuan, Ekelechi MacPepple, Temitope E. Adewuyi, Steven MacLennan, Alberto Coscione, and Eva M. Comp{\'e}rat have nothing to declare.",
year = "2018",
month = "7",
doi = "10.1016/j.eururo.2018.04.003",
language = "English",
volume = "74",
pages = "76--83",
journal = "European Urology",
issn = "0302-2838",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Risks and Benefits of Adjuvant Radiotherapy After Inguinal Lymphadenectomy in Node-positive Penile Cancer

T2 - A Systematic Review by the European Association of Urology Penile Cancer Guidelines Panel

AU - Robinson, Richard

AU - Marconi, Lorenzo

AU - MacPepple, Ekelechi

AU - Hakenberg, Oliver W.

AU - Watkin, Nick

AU - Yuan, Yuhong

AU - Lam, Thomas

AU - MacLennan, Steven

AU - Adewuyi, Temitope E.

AU - Coscione, Alberto

AU - Minhas, Suks S.

AU - Compérat, Eva M.

AU - Necchi, Andrea

N1 - Richard Robinson certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Dr. Thomas Lam is a company consultant for and has received company speaker honoraria from Pfizer, GSK, Astellas, and Ipsen. Mr. Suks S. Minhas receives company speaker honorarium for Lilly and has received a fellowship/medical travel grant from American Medical systems Fellowship. Dr. Andrea Necchi is a company consultant for and has received company speaker honoraria from Bayer and Astra Zeneca, and has received a fellowship/medical travel grant from Pierre Fabre; he has been involved with trial participation for Roche, Merck Sharp & Dohme, BMS, and Novartis, as well as receiving grants/research supports from GlaxoSmithKline and Millenium. Oliver Hakenberg, Nick Watkin, Richard Robinson, Yuhong Yuan, Ekelechi MacPepple, Temitope E. Adewuyi, Steven MacLennan, Alberto Coscione, and Eva M. Compérat have nothing to declare.

PY - 2018/7

Y1 - 2018/7

N2 - ContextManagement of men with penile squamous cell carcinoma (PSCC) who have high-risk features following radical inguinal lymphadenectomy (ILND) remains controversial. European Association of Urology guidelines state that adjuvant inguinal radiotherapy (AIRT) is “not generally recommended”. Despite this, many centres continue to offer AIRT to a subset of men.ObjectiveTo undertake a systematic review of the evidence on AIRT in node-positive men with PSCC.Evidence acquisitionA systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with no language or date restriction. Inclusion criteria were men with PSCC, pathologically staged inguinal node positive after ILND. The intervention included ILND with AIRT compared with ILND alone. Primary outcomes were relapse-free survival and toxicity. Risk of bias assessment was undertaken.Evidence synthesisA total of 913 abstracts were identified and screened independently by two reviewers. Seven studies were eligible for inclusion: six full-text manuscripts and one conference abstract. All were retrospective series and at a high risk of bias. The selected studies included 1605 men. Indications for AIRT varied but were typically involvement of two or more inguinal nodes or extranodal extension. Regional recurrence rate following AIRT was reported at 10–91.7%. Only one study reported on toxicity. Two studies compared recurrence and survival between men who received and who did not receive AIRT, with no significant difference (p > 0.05).ConclusionsThe evidence indicates that men treated with AIRT do not gain benefit with respect to relapse or survival. Uncertainty remains due to the retrospective nature and high risks of bias across the evidence. Given the lack of evidence supporting AIRT, it cannot be recommended for routine practice.Patient summaryMen with penile cancer who have involvement of the inguinal lymph nodes are at a high risk of cancer recurrence and death. We reviewed the literature to see if radiation treatment after removal of the nodes provided benefit. We did not find any good-quality evidence supporting this treatment, and hence it cannot be recommended.

AB - ContextManagement of men with penile squamous cell carcinoma (PSCC) who have high-risk features following radical inguinal lymphadenectomy (ILND) remains controversial. European Association of Urology guidelines state that adjuvant inguinal radiotherapy (AIRT) is “not generally recommended”. Despite this, many centres continue to offer AIRT to a subset of men.ObjectiveTo undertake a systematic review of the evidence on AIRT in node-positive men with PSCC.Evidence acquisitionA systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with no language or date restriction. Inclusion criteria were men with PSCC, pathologically staged inguinal node positive after ILND. The intervention included ILND with AIRT compared with ILND alone. Primary outcomes were relapse-free survival and toxicity. Risk of bias assessment was undertaken.Evidence synthesisA total of 913 abstracts were identified and screened independently by two reviewers. Seven studies were eligible for inclusion: six full-text manuscripts and one conference abstract. All were retrospective series and at a high risk of bias. The selected studies included 1605 men. Indications for AIRT varied but were typically involvement of two or more inguinal nodes or extranodal extension. Regional recurrence rate following AIRT was reported at 10–91.7%. Only one study reported on toxicity. Two studies compared recurrence and survival between men who received and who did not receive AIRT, with no significant difference (p > 0.05).ConclusionsThe evidence indicates that men treated with AIRT do not gain benefit with respect to relapse or survival. Uncertainty remains due to the retrospective nature and high risks of bias across the evidence. Given the lack of evidence supporting AIRT, it cannot be recommended for routine practice.Patient summaryMen with penile cancer who have involvement of the inguinal lymph nodes are at a high risk of cancer recurrence and death. We reviewed the literature to see if radiation treatment after removal of the nodes provided benefit. We did not find any good-quality evidence supporting this treatment, and hence it cannot be recommended.

KW - penile cancer

KW - adjuvant radiotherapy

KW - lymph nodes

U2 - 10.1016/j.eururo.2018.04.003

DO - 10.1016/j.eururo.2018.04.003

M3 - Article

VL - 74

SP - 76

EP - 83

JO - European Urology

JF - European Urology

SN - 0302-2838

IS - 1

ER -