Rethink Urologic Cancer Treatment in the Era of COVID-19

M. Alexander Otto

April 09, 2020

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

Curative treatments for metastatic prostate, renal, and urothelial cancer — and germ cell tumors — should continue as usual amid the COVID-19 pandemic, but "the risk/benefit ratio of a number of palliative and (neo)adjuvant treatments has to be reconsidered," according to an editorial set to be published in European Urology.

"Regimens with a clear survival advantage should be prioritized, with curative treatments remaining mandatory," wrote Silke Gillessen Sommer, MD, of Istituto Oncologico della Svizzera Italiana in Bellizona, Switzerland, and Thomas Powles, MD, of Barts Cancer Institute in London.

However, it may be appropriate to stop or delay therapies with modest or unproven survival benefits. "Delaying the start of therapy ... is an appropriate measure for many of the therapies in urology cancer," they wrote.

Timely Recommendations for Oncologists

The COVID-19 pandemic is limiting resources for cancer, noted Zachery Reichert, MD, PhD, a urological oncologist and assistant professor at the University of Michigan, Ann Arbor, who was asked for his thoughts about the editorial.

Oncologists and oncology nurses are being shifted to care for COVID-19 patients, space once devoted to cancer care is being repurposed for the pandemic, and personal protective equipment needed to prepare chemotherapies is in short supply.

Meanwhile, cancer patients are at increased risk of dying from the virus (Lancet Oncol. 2020;21:335-7), so there's a need to minimize their contact with the healthcare system to protect them from nosocomial infection, and a need to keep their immune system as strong as possible to fight it off.

To help cancer patients fight off infection and keep them out of the hospital, the editorialists recommended growth factors and prophylactic antibiotics after chemotherapy, palliative therapies at doses that avoid febrile neutropenia, discontinuing steroids or at least reducing their doses, and avoiding bisphosphonates if they involve potential COVID-19 exposure in medical facilities.

The advice in the editorial mirrors many of the discussions going on right now at the University of Michigan, Dr. Reichert said, and perhaps other oncology services across the United States.

It will come down to how severe the pandemic becomes locally, but he said it seems likely "a lot of us are going to be wearing a different hat for a while."

Patients who have symptoms from a growing tumor will likely take precedence at the university, but treatment might be postponed until after COVID-19 peaks if tumors don't affect quality of life. Also, bladder cancer surgery will probably remain urgent "because the longer you wait, the worse the outcomes," but perhaps not prostate and kidney cancer surgery, where delay is safer, Dr. Reichert said.

Prostate/Renal Cancers and Germ Cell Tumors

The editorialists noted that oral androgen receptor therapy should be preferred over chemotherapy for prostate cancer. Dr. Reichert explained that's because androgen blockade is effective, requires less contact with healthcare providers, and doesn't suppress the immune system or tie up hospital resources as much as chemotherapy. "In the world we are in right now, oral pills are a better choice," he said.

The editorialists recommended against both nephrectomy for metastatic renal cancer and adjuvant therapy after orchidectomy for stage 1 germ cell tumors for similar reasons, and also because there's minimal evidence of benefit.

Dr. Powles and Dr. Gillessen Sommer suggested considering a break from immune checkpoint inhibitors (ICIs) and oral vascular endothelial growth factors (VEGFs) for renal cancer patients who have been on them a year or two. It's something that would be considered even under normal circumstances, Dr. Reichert explained, but it's more urgent now to keep people out of the hospital. VEGFs should also be prioritized over ICIs; they have similar efficacy in renal cancer, but VEGFs are a pill.

They also called for oncologists to favor conventional-dose treatments for germ cell tumors over high-dose treatments, meaning bone marrow transplants or high-intensity chemotherapy. Amid a pandemic, the preference is for options "that don't require a hospital bed," Dr. Reichert said.

Table 1. Overview of Suggestions Regarding Systemic Therapy

 

Prostate cancer

Renal cancer

Germ cell tumors

Urothelial cancer

1. Treatment should be commenced where possible

Frontline treatment for metastatic disease

Treatment for frontline IMDC intermediate- and poor-risk disease metastatic diseasea

Treatment with curative intent

First-line treatment for metastatic disease

2. Treatment should not be commenced without justification

CTx in patients at significant COVID-19–related riskb

Nephrectomy for metastatic disease

Adjuvant therapy after orchidectomy for stage I disease

CTx in platinumrefractory disease Perioperative CTx for operable diseasec

3. Treatment should not be stopped without justification

AR-targeted therapyd

Treatment for frontline metastatic disease

First- and second-line treatment for metastatic disease

Treatment for frontline metastatic disease

4. Treatment that can potentially be stopped or delayed after careful consideratione

Minimizing the number of CTx cycles or prolonging cycle length may be justified

Steroids as a cancer therapy

ICI or oral VEGFtargeted therapy after prolonged period (1-2 yr)d

 

CTx for platinum refractory patients who are not responding to therapy

More than 3 CTx cycles in the perioperative stetting

5. Treatments that can be given preferentially compared to other options

Oral AR-targeted therapy rather than CTxf

Oral VEGF therapy rather than IV immune therapy

Conventional dose rather than high-dose therapy

ICIs rather than CTx in PD-L1–positive frontline metastatic disease

Abbreviations: AR, androgen receptor; CTx, chemotherapy; ICI, immune checkpoint inhibitor; IMDC, International Metastatic Renal Cell Carcinoma Database Consortium; IV, intravenous.

aOral VEGF-targeted therapy rather than IV ICIs may be attractive as it requires fewer healthcare interactions and resources.

bYounger cancer patients and those without comorbidities may be at lower risk, which should be considered.

cNeoadjuvant chemotherapy may be helpful in bridging time to surgery in cases in which elective surgery is not possible.

dRegimens with a longer interval (4-weekly nivolumab or 6-weekly pembrolizumab) should be used where possible.

ePalliative CTx was tested with a specific number of cycles. The risk associated with stopping before this has not been assessed, nor of the principles of delaying chemotherapy. There are subgroups of prostate and urothelial cancer patients for whom continuing CTx to the full number of cycles may be associated with more risk than benefit. Patients will need to participate in this discussion.

fAssuming similar efficacy between the regimens.

Urothelial Cancer

Dr. Powles and Dr. Gillessen Sommer suggested not starting or continuing second-line chemotherapies in urothelial cancer patients refractory to first-line platinum-based therapies. The chance they will respond to second-line options is low, perhaps around 10%. That might have been enough before the pandemic, but it's less justified amid resource shortages and the risk of COVID-19 in the infusion suite, Dr. Reichert explained.

Along the same lines, they also suggested reconsidering perioperative chemotherapy for urothelial cancer, and, if it's still a go, recommended against going past three cycles, as the benefits in both scenarios are likely marginal. However, if COVID-19 cancels surgeries, neoadjuvant therapy might be the right — and only — call, according to the editorialists.

They recommended prioritizing ICIs over chemotherapy in patients with metastatic urothelial cancer who are positive for programmed death-ligand 1 (PD-L1). PD-L1–positive patients have a good chance of responding, and ICIs don't suppress the immune system.

"Chemotherapy still has a slightly higher percent response, but right now, this is a better choice for" PD-L1–positive patients, Dr. Reichert said.

Dr. Gillessen Sommer and Dr. Powles disclosed ties to Bristol-Myers Squibb, Roche, and numerous other companies. Dr. Reichert has no relevant disclosures.

Eur Urol. In press, 2020. Full text

Contact M. Alexander Otto at aotto@mdedge.com. This article first appeared on MDedge.com.

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