European Urology - Advice for Medical Oncology care of Urological cancer patients during the COVID-19 pandemic.

1. European Urology
Advice for Medical Oncology care of Urological cancer patients during the COVID-19
pandemic
--Manuscript Draft--
Manuscript Number: EURUROL-D-20-00382
Article Type: Editorial
Keywords: COVID-19, Chemotherapy, Immunotherapy, Urological Cancer
Corresponding Author: Silke Gillessen, M.D.
Istituto Oncologico della Svizzera Italiana
Bellinzona, SWITZERLAND
First Author: Silke Gillessen, M.D.
Order of Authors: Silke Gillessen, M.D.
Silke Gillessen Sommer
Thomas Powles
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2. Gillessen: Honoraria: Janssen Consulting or Advisory Role: Astellas Pharma (Inst),
Curevac (Inst), Novartis (Inst), Active Biotech (Inst), Bristol-Myers Squibb (Inst),
Ferring (Inst), MaxiVax, Advanced Accelerator Applications, Roche, Janssen (Inst),
Innocrin Pharma
(Inst), Sanofi, Bayer (Inst), Orion Pharma GmbH, Clovis Oncology (Inst), Menarini
Silicon Biosystems (Inst) Patents, Royalties, Other Intellectual Property: Method for
biomarker (WO 3752009138392 A1) Other Relationship: Nektar, ProteoMediX
Powles: TBS
Disclosure

3. Advice for systemic therapy in patients with Urological cancers during the COVID-19 pandemic
Silke Gillessen Sommer 1
and Thomas Powles 2
1. Istituto Oncologico della Svizzera Italiana (IOSI), Bellinzona, Switzerland
2. Barts Cancer Institute, London, UK
Evidence suggests that cancer patients are at increased risk of death from COVID19 [1]. Therefore,
during this pandemic, the risk/benefit ratio of a number of palliative and (neo)adjuvant treatments
has to be reconsidered. The duration of this period and detail of the risk remain to be determined. A
number of factors such as age and co-morbidities will also influence this risk, as will the additional
visits to hospital associated with specific treatment [2,3].
The advice set out in this document gives suggestions during the period of risk. It should not be
considered as rigid guidelines in the traditional sense, more a pragmatic perspective of this
risk/benefit ratio in specific clinical scenarios. Also this advice will not apply to all patients, as there
are a number of variables including the stage of the pandemic and the local healthcare capacity, the
risk of infection to the individual, the status of the cancer, comorbidities, age and the details of the
treatment [4]. This document only focuses on the last of these factors.
Minimising potential exposure to COVID19 via reduced visits to hospital, particularly for intravenous
or inpatient therapy, is relevant. This is particularly important during the initial phase of the pandemic
where incidence is increasing exponentially and the upcoming pressure on healthcare resource
unknown [4]. Predicting the status of healthcare facilities and the ability to deliver systemic therapy
in the future requires consideration. These factors will vary by geographical region.
There are a number of factors which require consideration. Regimens with a clear survival advantage
should be prioritised, with curative treatments remaining mandatory and others requiring
consideration of the risk/benefit ratio. Treatments that have only shown a palliative effect for patients
who are symptomatic with symptoms require careful discussion. Delaying the start of therapy during
periods of uncertainty or difficulty is an appropriate measure for many of the therapies in urology
cancer.
For curative treatments application of growth factors and prophylactic antibiotics should be
considered to avoid hospitalisation. Palliative treatments should be given in a dose intensity that
avoids febrile neutropenia. While we do not recommend suboptimal dosing, if neutropenia occurs the
doses need to be reduced for each episode. Prophylactic antibiotics are recommended where
appropriate. Immune suppressive agents like steroids should be avoided or reduced for anti-emesis
Manuscript

4. where possible. Prolonged steroid treatment for prostate cancer requires consideration. Agents
reducing incidence of skeletal related events such as bisphosphonates are probably best avoided if it
involves potential exposure to COVID19 while giving the therapy.
Adjuvant and neoadjuvant treatment require particular attention. The risk/benefit ratio may favour
not giving therapy if survival benefits are modest or unproven, such as perioperative therapy in
urothelial cancer. Conversely, neoadjuvant therapy may be attractive in delaying the need for
surgery/radiotherapy where these services are interrupted.
Aspects of clinical trials may not be appropriate in this pandemic. Recruitment into clinical trials
requires careful consideration. Halting recruitment into cancer trials to divert resources to fight the
pandemic may be appropriate.
The landscape will change as risk of infection alters and more is known about preventing and treating
COVID19. Also treatments for COVID19, such as antivirals may improve outcomes. It is hoped that the
advice in this document will quickly become redundant.

5. Prostate cancer Renal cancer Germ cell tumors Urothelial cancer
1. Treatment
should be
commenced
where
possible
Front line
treatment for
metastatic
disease
Treatment for
front line IMDC
intermediate and
poor risk disease
metastatic
disease b
Treatment with
curative intent
Frist line
treatment for
metastatic
disease.
2. Treatment
should not
be
commenced
without
justification.
Chemotherapy in
patients at
significant COVID
related risk
d
Nephrectomy for
metastatic
disease
Adjuvant therapy
post
orchidectomy
for Stage I
disease
CT in platinum
refractory
disease.
Perioperative CT
for operable
disease a
3. Treatment
should not
be stopped
without
justification
Androgen-
receptor
targeted therapy
c
.
Treatment for
front line
metastatic
disease.
Frist and 2nd
line
treatment for
metastatic
disease
Treatment for
front line
metastatic
disease
4. Treatment
can
potentially
be stopped
or delayed
after careful
consideration
Minimising the
number of cycles
of CT or
prolonging cycle
length may be
justified.
Steroids as a
cancer therapy.
Immune
checkpoint
inhibition or oral
VEGF targeted
therapy after
prolonged period
(1-2 yrs) c
CT for platinum
refractory
patients who are
not responding
to therapy
Greater than 3
cycles of CT in
the perioperative
stetting.
5. Treatments
which can be
given
preferentially
compared to
other options
Oral androgen
Receptor
targeted therapy
rather than CTe
Oral VEGF
therapy rather
than IV immune
therapy
Conventional
dose rather than
high dose
therapy
ICIs rather than
CT in PD-L1
positive front line
metastatic
disease.
Key: CT= chemotherapy ICI = immune checkpoint inhibitor.
a. Neoadjuvant chemotherapy may be helpful to bridge time to surgery in cases were elective surgery
is not possible.
b. Oral vascular endothelial growth factor targeted therapy rather than intravenous immune
checkpoint inhibitors may be attractive as it requires less healthcare interaction and resource.
c. Regimens with longer interval (4 weekly nivolumab or 6 weekly pembrolizumab) should be
employed where possible..
d. Younger cancer patients, and those without comorbidities may be at less risk which requires
consideration.
e. Assuming similar efficacy between the regimens.
f. Palliative chemotherapy was tested with specific number of cycles. The risk associated with stopping
prior to this has not been assessed. Nor has the principles of delaying chemotherapy. There are

6. subgroups of prostate and urothelial cancer patients where continuing chemotherapy to the full
number of cycles may be associated with more risk than benefit. Patients will need to participate in
this discussion.

7. References
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Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with
COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 11. pii: S0140-
6736(20)30566-3.
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KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH,
Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical
Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N
Engl J Med. 2020 Feb 28
4 Anderson RM, Heesterbeek H, Klinkenberg D, Hollingsworth TD. How will country-based mitigation
measures influence the course of the COVID-19 epidemic? Lancet. 2020 Mar 9. pii: S0140-
6736(20)30567-5.