Risks from Deferring Treatment for Genitourinary Cancers: A Collaborative Review to Aid Triage and Management During the COVID-19 Pandemic

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Abstract

Context

The coronavirus disease 2019 (COVID-19) pandemic is leading to delays in the treatment of many urologic cancers.

Objective

To provide a contemporary picture of the risks from delayed treatment for urologic cancers to assist with triage.

Evidence acquisition

A collaborative review using literature published as of April 2, 2020.

Evidence synthesis

Patients with low-grade non–muscle-invasive bladder cancer are unlikely to suffer from a 3–6-month delay. Patients with muscle-invasive bladder cancer are at risk of disease progression, with radical cystectomy delays beyond 12 wk from diagnosis or completion of neoadjuvant chemotherapy. Prioritization of these patients for surgery or management with radiochemotherapy is encouraged. Active surveillance should be used for low-risk prostate cancer (PCa). Treatment of most patients with intermediate- and high-risk PCa can be deferred 3–6 mo without change in outcomes. The same may be true for cancers with the highest risk of progression. With radiotherapy, neoadjuvant androgen deprivation therapy (ADT) is the standard of care. For surgery, although the added value of neoadjuvant ADT is questionable, it may be considered if a patient is interested in such an approach. Intervention may be safely deferred for T1/T2 renal masses, while locally advanced renal tumors (≥T3) should be treated expeditiously. Patients with metastatic renal cancer may consider vascular endothelial growth factor targeted therapy over immunotherapy. Risks for delay in the treatment of upper tract urothelial cancer depend on grade and stage. For patients with high-grade disease, delays of 12 wk in nephroureterectomy are not associated with adverse survival outcomes. Expert guidance recommends expedient local treatment of testis cancer. In penile cancer, adverse outcomes have been observed with delays of ≥3 mo before inguinal lymphadenectomy. Limitations include a paucity of data and methodologic variations for many cancers.

Conclusions

Patients and clinicians should consider the oncologic risk of delayed cancer intervention versus the risks of COVID-19 to the patient, treating health care professionals, and the health care system.

Patient summary

The coronavirus disease 2019 pandemic has led to delays in the treatment of patients with urologic malignancies. Based on a review of the literature, patients with high-grade urothelial carcinoma, advanced kidney cancer, testicular cancer, and penile cancer should be prioritized for treatment during these challenging times.

Take Home Message

The coronavirus disease 2019 (COVID-19) pandemic is leading to delays in the treatment of many urologic cancers. Patients and clinicians should consider the oncologic risk of delayed cancer intervention versus the risks of COVID-19 to patients, treating health care professionals, and the health care system.

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Most cited references 85

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Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China

Wenhua Liang, Weijie Guan, Ruchong Chen … (2020)

China and the rest of the world are experiencing an outbreak of a novel betacoronavirus known as severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). 1 By Feb 12, 2020, the rapid spread of the virus had caused 42 747 cases and 1017 deaths in China and cases have been reported in 25 countries, including the USA, Japan, and Spain. WHO has declared 2019 novel coronavirus disease (COVID-19), caused by SARS-CoV-2, a public health emergency of international concern. In contrast to severe acute respiratory system coronavirus and Middle East respiratory syndrome coronavirus, more deaths from COVID-19 have been caused by multiple organ dysfunction syndrome rather than respiratory failure, 2 which might be attributable to the widespread distribution of angiotensin converting enzyme 2—the functional receptor for SARS-CoV-2—in multiple organs.3, 4 Patients with cancer are more susceptible to infection than individuals without cancer because of their systemic immunosuppressive state caused by the malignancy and anticancer treatments, such as chemotherapy or surgery.5, 6, 7, 8 Therefore, these patients might be at increased risk of COVID-19 and have a poorer prognosis. On behalf of the National Clinical Research Center for Respiratory Disease, we worked together with the National Health Commission of the People's Republic of China to establish a prospective cohort to monitor COVID-19 cases throughout China. As of the data cutoff on Jan 31, 2020, we have collected and analysed 2007 cases from 575 hospitals (appendix pp 4–9 for a full list) in 31 provincial administrative regions. All cases were diagnosed with laboratory-confirmed COVID-19 acute respiratory disease and were admitted to hospital. We excluded 417 cases because of insufficient records of previous disease history. 18 (1%; 95% CI 0·61–1·65) of 1590 COVID-19 cases had a history of cancer, which seems to be higher than the incidence of cancer in the overall Chinese population (285·83 [0·29%] per 100 000 people, according to 2015 cancer epidemiology statistics 9 ). Detailed information about the 18 patients with cancer with COVID-19 is summarised in the appendix (p 1). Lung cancer was the most frequent type (five [28%] of 18 patients). Four (25%) of 16 patients (two of the 18 patients had unknown treatment status) with cancer with COVID-19 had received chemotherapy or surgery within the past month, and the other 12 (25%) patients were cancer survivors in routine follow-up after primary resection. Compared with patients without cancer, patients with cancer were older (mean age 63·1 years [SD 12·1] vs 48·7 years [16·2]), more likely to have a history of smoking (four [22%] of 18 patients vs 107 [7%] of 1572 patients), had more polypnea (eight [47%] of 17 patients vs 323 [23%] of 1377 patients; some data were missing on polypnea), and more severe baseline CT manifestation (17 [94%] of 18 patients vs 1113 [71%] of 1572 patients), but had no significant differences in sex, other baseline symptoms, other comorbidities, or baseline severity of x-ray (appendix p 2). Most importantly, patients with cancer were observed to have a higher risk of severe events (a composite endpoint defined as the percentage of patients being admitted to the intensive care unit requiring invasive ventilation, or death) compared with patients without cancer (seven [39%] of 18 patients vs 124 [8%] of 1572 patients; Fisher's exact p=0·0003). We observed similar results when the severe events were defined both by the above objective events and physician evaluation (nine [50%] of 18 patients vs 245 [16%] of 1572 patients; Fisher's exact p=0·0008). Moreover, patients who underwent chemotherapy or surgery in the past month had a numerically higher risk (three [75%] of four patients) of clinically severe events than did those not receiving chemotherapy or surgery (six [43%] of 14 patients; figure ). These odds were further confirmed by logistic regression (odds ratio [OR] 5·34, 95% CI 1·80–16·18; p=0·0026) after adjusting for other risk factors, including age, smoking history, and other comorbidities. Cancer history represented the highest risk for severe events (appendix p 3). Among patients with cancer, older age was the only risk factor for severe events (OR 1·43, 95% CI 0·97–2·12; p=0·072). Patients with lung cancer did not have a higher probability of severe events compared with patients with other cancer types (one [20%] of five patients with lung cancer vs eight [62%] of 13 patients with other types of cancer; p=0·294). Additionally, we used a Cox regression model to evaluate the time-dependent hazards of developing severe events, and found that patients with cancer deteriorated more rapidly than those without cancer (median time to severe events 13 days [IQR 6–15] vs 43 days [20–not reached]; p<0·0001; hazard ratio 3·56, 95% CI 1·65–7·69, after adjusting for age; figure). Figure Severe events in patients without cancer, cancer survivors, and patients with cancer (A) and risks of developing severe events for patients with cancer and patients without cancer (B) ICU=intensive care unit. In this study, we analysed the risk for severe COVID-19 in patients with cancer for the first time, to our knowledge; only by nationwide analysis can we follow up patients with rare but important comorbidities, such as cancer. We found that patients with cancer might have a higher risk of COVID-19 than individuals without cancer. Additionally, we showed that patients with cancer had poorer outcomes from COVID-19, providing a timely reminder to physicians that more intensive attention should be paid to patients with cancer, in case of rapid deterioration. Therefore, we propose three major strategies for patients with cancer in this COVID-19 crisis, and in future attacks of severe infectious diseases. First, an intentional postponing of adjuvant chemotherapy or elective surgery for stable cancer should be considered in endemic areas. Second, stronger personal protection provisions should be made for patients with cancer or cancer survivors. Third, more intensive surveillance or treatment should be considered when patients with cancer are infected with SARS-CoV-2, especially in older patients or those with other comorbidities.

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Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials.

Richard J. Sylvester, Adrian P.M. van der Meijden, Willem Oosterlinck … (2006)

To provide tables that allow urologists to easily calculate a superficial bladder cancer patient's short- and long-term risks of recurrence and progression after transurethral resection. A combined analysis was carried out of individual patient data from 2596 superficial bladder cancer patients included in seven European Organization for Research and Treatment of Cancer trials. A simple scoring system was derived based on six clinical and pathological factors: number of tumors, tumor size, prior recurrence rate, T category, carcinoma in situ, and grade. The probabilities of recurrence and progression at one year ranged from 15% to 61% and from less than 1% to 17%, respectively. At five years, the probabilities of recurrence and progression ranged from 31% to 78% and from less than 1% to 45%. With these probabilities, the urologist can discuss the different options with the patient to determine the most appropriate treatment and frequency of follow-up.

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Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial

David Dearnaley, Isabel Syndikus, Helen Mossop … (2016)

Summary Background Prostate cancer might have high radiation-fraction sensitivity that would give a therapeutic advantage to hypofractionated treatment. We present a pre-planned analysis of the efficacy and side-effects of a randomised trial comparing conventional and hypofractionated radiotherapy after 5 years follow-up. Methods CHHiP is a randomised, phase 3, non-inferiority trial that recruited men with localised prostate cancer (pT1b–T3aN0M0). Patients were randomly assigned (1:1:1) to conventional (74 Gy delivered in 37 fractions over 7·4 weeks) or one of two hypofractionated schedules (60 Gy in 20 fractions over 4 weeks or 57 Gy in 19 fractions over 3·8 weeks) all delivered with intensity-modulated techniques. Most patients were given radiotherapy with 3–6 months of neoadjuvant and concurrent androgen suppression. Randomisation was by computer-generated random permuted blocks, stratified by National Comprehensive Cancer Network (NCCN) risk group and radiotherapy treatment centre, and treatment allocation was not masked. The primary endpoint was time to biochemical or clinical failure; the critical hazard ratio (HR) for non-inferiority was 1·208. Analysis was by intention to treat. Long-term follow-up continues. The CHHiP trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN97182923. Findings Between Oct 18, 2002, and June 17, 2011, 3216 men were enrolled from 71 centres and randomly assigned (74 Gy group, 1065 patients; 60 Gy group, 1074 patients; 57 Gy group, 1077 patients). Median follow-up was 62·4 months (IQR 53·9–77·0). The proportion of patients who were biochemical or clinical failure free at 5 years was 88·3% (95% CI 86·0–90·2) in the 74 Gy group, 90·6% (88·5–92·3) in the 60 Gy group, and 85·9% (83·4–88·0) in the 57 Gy group. 60 Gy was non-inferior to 74 Gy (HR 0·84 [90% CI 0·68–1·03], pNI=0·0018) but non-inferiority could not be claimed for 57 Gy compared with 74 Gy (HR 1·20 [0·99–1·46], pNI=0·48). Long-term side-effects were similar in the hypofractionated groups compared with the conventional group. There were no significant differences in either the proportion or cumulative incidence of side-effects 5 years after treatment using three clinician-reported as well as patient-reported outcome measures. The estimated cumulative 5 year incidence of Radiation Therapy Oncology Group (RTOG) grade 2 or worse bowel and bladder adverse events was 13·7% (111 events) and 9·1% (66 events) in the 74 Gy group, 11·9% (105 events) and 11·7% (88 events) in the 60 Gy group, 11·3% (95 events) and 6·6% (57 events) in the 57 Gy group, respectively. No treatment-related deaths were reported. Interpretation Hypofractionated radiotherapy using 60 Gy in 20 fractions is non-inferior to conventional fractionation using 74 Gy in 37 fractions and is recommended as a new standard of care for external-beam radiotherapy of localised prostate cancer. Funding Cancer Research UK, Department of Health, and the National Institute for Health Research Cancer Research Network.

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Author and article information

Contributors

James W.F. Catto

Zachary Klaassen

Journal

Journal ID (nlm-ta): Eur Urol

Journal ID (iso-abbrev): Eur. Urol

Title: European Urology

Publisher: Published by Elsevier B.V. on behalf of European Association of Urology.

ISSN (Print): 0302-2838

ISSN (Electronic): 1873-7560

Publication date PMC-release: 3 May 2020

Publication date (Electronic): 3 May 2020

Affiliations

[a ]Department of Urology, Vanderbilt University Medical Center, Nashville, TN, USA

[b ]Department of Surgery, Oncology, and Gastroenterology—Urology Clinic, University of Padua, Padua, Italy

[c ]Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

[d ]Royal Free London NHS Foundation Trust, UCL Division of Surgery and Interventional Science, London, UK

[e ]Department of Urology, MD Anderson Cancer Center, Houston, TX, USA

[f ]Department of Urology, Mayo Clinic, Rochester, MN, USA

[g ]Department of Urology, University of Michigan, Ann Arbor, MI, USA

[h ]Department of Urology, University hospital Nord, St Etienne, France

[i ]Department of Medical Oncology, Istituto Oncologico della Svizzera Italiana, Bellinzona, Switzerland

[j ]Università della Svizzera Italiana, Lugano, Switzerland

[k ]Department of Radiation Oncology, Institut Gustave Roussy, Villejuif, France

[l ]Urology, GRC n°5, PREDICTIVE ONCO-URO, AP-HP, Pitié Salpetriere Hospital, Sorbonne University, Paris, France

[m ]European Section of Onco Urology, EAU

[n ]Barts Cancer Center, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK

[o ]Academic Urology Unit, University of Sheffield, Sheffield, UK

[p ]Department of Surgery, Division of Urology, Augusta University—Medical College of Georgia, Augusta, GA, USA

[q ]Georgia Cancer Center, Augusta, GA, USA

Author notes

[* ]Corresponding authors. Georgia Cancer Center, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA. Tel. +1 706 721 2519; Fax: +1 706 721 2548 (Z. Klaassen). Academic Unit of Urology, The Medical School, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK. Tel. +44 114 226 1229; Fax: +44 114 271 2268 (J.W.F. Catto). j.catto@ 123456sheffield.ac.uk zklaassen19@ 123456gmail.com

Article

Publisher ID: S0302-2838(20)30331-6

DOI: 10.1016/j.eururo.2020.04.063

PMC ID: 7196384

PubMed ID: 32414626

SO-VID: 4c49f19e-4e48-448e-b942-51f780900b8b

License:

Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

Risks from Deferring Treatment for Genitourinary Cancers: A Collaborative Review to Aid Triage and Management During the COVID-19 Pandemic

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Abstract

Context

Objective

Evidence acquisition

Evidence synthesis

Conclusions

Patient summary

Take Home Message

Related collections

Novel Coronavirus Disease COVID-19

Most cited references 85

Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China

Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials.

Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial

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