Christopher Wallis:  Hello, and thank you for joining us for this UroToday Journal Club. Today, we are talking about The Impact of the COVID-19 Pandemic on GU Cancer Care: Re-envisioning the Future. I'm Chris Wallis. I'm a fellow in urological oncology at Vanderbilt, and I'm joined by Zach Klaassen, an Assistant Professor in the Division of Urology at MCG. We both are co-authors on this paper which was a large collaborative review with some of the thought leaders in GU oncology, including urologists, medical oncologists, radiation oncologists, as well as also colleagues from primary care.

By way of a bit of background, let's summarize what we've seen in healthcare delivery and in the society as a result of the COVID-19 pandemic. First, there was an initial heavy surge and demand for healthcare resources and concern regarding the limited health systems' capacity and overwhelmed hospitals. And this was particularly noted in jurisdictions such as Italy and in New York City. As a result of both the need to triage care in those jurisdictions, as well as the goal of avoiding overwhelming healthcare systems in other regions, medical government bodies recommended reprioritizing surgical cases for the conservation of both PPE, as well as personnel resources. As a result, we were in the position of having to balance the risk of COVID-19 infection and its equali against the risk of delayed surgery and risks to the healthcare system with limited resources.

We know that the characteristics of patients with GU cancers near those who are at increased risk of COVID-19 and a severe phenotype of COVID-19. Looking at patients admitted to ICUs in Lombardy, Italy, we see a demographic picture that looks much like the patients we treat, with the median age in the 60s, a predominance of men with comorbidities. And in these patients mortality rates were high.

In addition, the international collaborative COVID surge looked at mortality in pulmonary complications among patients who underwent surgery with peri-operative COVID-19 infection. And in this international cohort of just over 1100 patients, both men and women undergoing emergent and elective operations, just over a quarter had confirmed COVID-19 infection preoperatively. A 30-day mortality rate of nearly 24% is far in excess of what we would expect from most elective or even emergent operations. And notably, factors associated with increased 30-day mortality in these patients included, again, those characteristics we see in our GU oncology patients with male sex, older age, comorbidities, or medical fragility, as well as the necessity for an oncology-based operation conferring a 55% increased likelihood. So an odds ratio of 1.55.

As a result of these considerations, there's been the need in the last six months to triage GU oncology care. And so many pieces of work could come out in this space, and this is one we want to highlight that we were part of as a collaborative view in a European Urology, looking at the risks of deferring treatment in GU cancers. And we know that in bladder cancer, it's reasonable to delay treatment for patients with low grade non-muscle invasive disease. Whereas for those with a high-grade disease or muscle-invasive bladder cancer, treatment delays are likely to adversely affect patient outcomes. And so we felt that the evidence supported moving forward with these patients' care.

In the case of prostate cancer, low-risk patients, whether in COVID times or not, should be offered doctor surveillance and patients with intermediate and high-risk disease can safely be deferred. Moving to kidney cancer. Again, small renal masses are likely safe to defer treatment. And for this reason, active surveillance is a recognized approach for these patients, regardless of any pandemic concerns. In T2 kidney cancers, again, likely safe to defer treatment although the evidence base for this is much more sparse. For patients with advanced kidney cancer as a locally advanced disease, there's essentially no evidence assessing the safety of a deferred treatment. And so we recommended moving forward with treatment as per routine practice.

For patients with metastatic disease, the medical oncologists in this group felt that VEGF targeted therapy, particularly where it could be achieved orally, has benefits over immunotherapy with the immune-mediated adverse events that may potentially require hospitalization and ICU stays. In upper tract urothelial, it's again likely safe to defer treatment of low-grade disease. Whereas prolonged delays for those with high grade more advanced disease are likely to be harmful to patients. And so we recommended moving forward with delays of no more than 12 weeks.

In testis cancer, there's a paucity of evidence, but in general, the feeling among the expert consensus was to move forward with treatment where indicated. And in penile cancer, again, local treatment as soon as possible and [inaudible] within three months was advised. Although again, there's a fair paucity of data in this space.

So the ongoing pandemic has many implications. At the institutional level, financial losses particularly felt in the United States, have resulted in workforce reductions. Social distancing policies have decreased the number of patients that are entering the healthcare system. And this has delayed or deferred workup and treatment both in the screening entry and actual treatment context, as well as reducing person contact, even within ongoing healthcare interactions.

As yet, the true impact of the pandemic on GU cancer care is yet to be fully realized as many patients with a deferred diagnosis have yet to present. And we have an unknown effect of the delays in diagnosis and treatment on both cancer-related and quality of life-related outcomes. However, changes in healthcare delivery as a result of the pandemic do offer, in some cases, potential benefits to both treating physicians, as well as patients. And so, leveraging these going forward may offer the opportunity to realize some longterm benefits in healthcare delivery, as a result of the lessons learned adapting to this pandemic.

And so in this manuscript, we sought to provide an evidence-informed expert driver review of GU cancer care moving forward, following initial adjustments in healthcare delivery as a result of the COVID-19 pandemic. And so this figure summarizes the considerations that we felt were most prominent. The most tangible change is likely in the delivery of care. And so we've seen a move towards telemedicine and decreased healthcare interactions in many jurisdictions. Although not widely adopted, single visit consultations with integrated radiology assessment and clinical consultation have already been undertaken. And doing this may reduce the burden of healthcare visits in a beneficial way for both patients and healthcare systems.

In addition, telemonitoring is sort of the next step beyond telemedicine, allowing for early discharge from hospitals with ongoing surveillance of vital signs parameters and the ability to have early identification of complications as they may arise. This allows for a hospital-at-home type environment.

And then the most familiar change in the delivery of care would be the transition to telemedicine. This has been assessed perhaps the best of any of these components and has been used in both the initial counseling and treatment choice assessment, as well as ongoing follow-up surveillance and survivorship domains.

In terms of adaptation of services, I think we need to be acutely aware of the effects of the changes in our care delivery, particularly with respect to mental health and the distancing between patients and their physicians. As well as also the loss of social supports for patients. And as well as the effect of social distancing on research initiatives.

Finally, we can look at how treatment decisions may differ as a result of the considerations as a result of the pandemic. And so we may prioritize more conservative treatment approaches with an increasing awareness of competing risks of mortality, as well as increase our efficiency of care. And we'll dive into each of these in a little more detail.

So in terms of remote interactions, the use of telemedicine in urology is relatively uncommon. This has been assessed, however, both in individual studies, as well as in systematic reviews. Most studies have focused on prostate cancer. And so this has looked at decision aids, such as the P3P tool in PSA followup and in survivorship studies. It's worth noting that in each of these settings, the use of telemedicine has been to complement rather than supplant in-person interactions. And so, rolling this out into a role where telemedicine usurps the standard inpatient interaction has not truly been assessed.

Telemedicine obviously has limitations in terms of the ability to perform clinical examinations. However, how this impacts actual clinical care is a little bit less clear. And in a setting like prostate cancer, we're obviously unable to do a digital rectal examination, but palpable exam findings may be less important with the widespread use of multiparametric MRI. Certainly, in testis and penile cancer, the clinical exam will remain important, but in kidney and bladder cancer, our feeling was that it was less likely to impact management as these decisions are often based on imaging findings in kidney cancer and in bladder cancer based on pathology results and potentially examination under anesthesia, which would not be affected by a move from a clinical evaluation in the clinic to a telemedicine-based consultation.

There are some advantages obviously to telemedicine. This has a convenience factor for both. For particularly patients, but also for clinicians in the right environment, definitely improves access for patients with long commutes and full-time employment. Numerous studies have shown that it is less time consuming for patients and can provide tertiary level care for patients who may be long distances from these facilities. Additionally thinking perhaps more broadly, telemedicine has the potential to reduce carbon emissions and reduce some of the detrimental effects of the healthcare system on our environment.

However, there are obvious disadvantages. So most of these come through the remote nature of the physician and patient interaction. As most who treat GU cancers will be familiar, there's a significant portion of our day that involves the delivery of bad news. And this is somewhat more difficult in the context of a telemedicine-based interaction. Both patients and physicians may lose important non-verbal cues, and it may be more difficult to clearly communicate in an empathic manner. In addition to this individual interaction-based difficulty, the transition to telemedicine may also exacerbate existing healthcare disparities.

Obviously there's a need for the technology to allow the use of a telemedicine platform, but there's also a need for the technological proficiency to utilize that platform. And so this may be particularly challenging for elderly patients, those for whom English is not their first language, and those with other socioeconomic marginalization factors. Recent work has suggested that in the Medicare population this may be more than a quarter of the patients we see. And so we need to take care that a transition to telemedicine, while convenient for many, may exacerbate our existing healthcare disparities. And we need to be particularly mindful of how we can roll this out in a way that does not harm these already marginalized patients.

Further, in the context of telemedicine, the ongoing evolutions in the issues related to privacy and confidentiality, as well as billing and remuneration. These are particularly important in the US healthcare context, in which many payers initially approved telemedicine-based interactions for a limited period of time and we will have to reevaluate the ongoing remuneration issues in this as this pandemic continues to play out over the coming months.

Beyond individual clinical interactions in a telemedicine approach, virtual interactions have taken on many other prominent roles in the life of a clinician treating GU oncology patients. Remote multidisciplinary tumor boards have become the norm in most jurisdictions and most institutions. However, other approaches such as electronic consultations in which there's the interaction between two physicians without direct interaction with the patient may also improve specialty expertise, particularly in remote environments.

Finally, virtual education has also blossomed in the last six months with collaborative teaching sessions through a variety of means as well as virtual conferences, which may be more accessible to many practitioners, while losing some of the networking based benefits of in-person conferences.

Beyond how we deliver care, there's the question of optimizing which care we deliver. And so, active surveillance, or conservative expectant management choices, are increasingly used in low and favorable intermediate-risk prostate cancer and small renal masses, and also in low-grade non-muscle-invasive bladder cancer. And these approaches take a nuanced consideration of the balance of oncologic risk from the cancer and competing risks from co-morbidity. And I think the current COVID-19 pandemic has refocused our assessment of competing risks such that conservative approaches have become more appealing for both many patients as well as many physicians.

So when we look at treatment administration for those patients who do offer therapy, there are many ways in which we can increase the efficiency of treatment in ways that may benefit the patient longterm. Within the context of prostate cancer, delivery of radiotherapy with hypofractionation has been proven to be equivalent both in terms of oncologic outcomes, as well as functional outcomes the longer [inaudible] and obviously offers a patient benefit with decreased visits to the hospital. ADT, when indicated, can be more conveniently administered using long-duration formulations, as opposed to monthly injections. For patients with high-grade non-muscle invasive bladder cancer, recent guidance has suggested that we prioritize the use of BCG. For those who are getting induction and early maintenance and use intravesical chemotherapy for patients with a lower risk of recurrence and progression.

Finally, there was an initial early concern with the use of laparoscopy and robotic surgery with concerns that this may be an aerosolizing procedure early in the COVID-19 pandemic. More recently it's been assessed that this is a safe approach. However, the SAGES group recommends the use of filtration for the release of insufflation related carbon dioxide in order to reduce any risk further.

In the context of systemic therapy, we have guidance from Doctor Gillison and Doctor Pauls regarding the use of systemic therapy at this time. Certainly prioritizing treatment with curative intent, as opposed to palliative intent, seems logical. And it's also worthwhile considering the impact of delayed treatment on primary out regimes of a high risk of febrile neutropenia. For example, a dose [inaudible] as compared to [inaudible]. It may be worthwhile considering optimizing using a dose reduction and calming stimulating factors in order to reduce the likelihood that these patients would require a significant healthcare resource that may be currently diverted to the use of treating patients with COVID-19.

As a result, we should also consider the risks of toxicity as well as the oncologic benefits of these systemic therapies. And so we should only be using those with high risks of toxicity in the setting of health care systems that are at a capacity level that allows them to manage the side effects. And again, the new adjuvant and adjuvant settings, these should only be used where they have proven survival benefits.

As we discussed in the context of surveillance-based protocols, consideration of the patient's health status and risks associated with COVID-19, as well as other comorbidities should be evaluated prior to embarking on systemic therapy. And the authors recommended that COVID-19 testing should be performed prior to the initiation of systemic therapy.

In addition to de- intensifying initial treatment, we can also de-intensify followup. And so, when we look at the PROTECT study, they took an active monitoring approach rather than a more invasive, active surveillance approach and suggested fewer less rigid surveillance with fewer biopsies and multiparametric MRI may allow for similarly positive outcomes. And so we can consider de-intensifying our surveillance regimes. Further, for patients who have undergone primary treatment for prostate cancer, virtual followup with remote PSA lab testing, and fewer in-person visits may reduce COVID-19 related risks, but also improve patient convenience while not harming our ability to follow both oncologic and functional outcomes.

For patients with non-muscle invasive disease, recent evidence that suggests a less stringent cystoscopic surveillance regime may not actually affect oncologic outcomes but will reduce patient burden as well as the number of repeat TURs. And again, the Mayo Group has come up with some algorithms to allow for risk-adjusted postsurgical surveillance for patients with kidney cancer allowing de-intensification associated with increasing patient co-morbidity.

I'm now going to pass over to Doctor Klaassen to consider further implications with respect to the mental health effects of the COVID-19 pandemic.

Zachary Klaassen: Thanks, Chris. So as you've been alluded to previously with the summary figure, there are significant mental health effects. And this isn't just for providers and patients, but for everybody, in general, who has been dealing with this pandemic. Certainly, social distancing has led to significant stress, loss of motivation, loss of meaning, and self-worth. And this is certainly evident in our oncology patients and even in our oncology providers. Early studies, looking at those that may be affected most by social distancing include women and younger patients.

Certainly, in oncology patients, there's the anxiety of expected management. And certainly, when we're counseling men about active surveillance for prostate cancer, which is the appropriate management, there's the concept of forgoing treatment, which may add psychological burden, especially in these times where there may be rationing of resources. In terms of active surveillance for prostate cancer and small renal masses, there's mixed literature regarding the mental health burden, but certainly, all of these will be amplified during the pandemic.

In terms of the impact of psychiatric conditions in those with oncology and oncology patients, Chris and I were previously a part of a study based in Ontario, Canada, which looked at patients with preexisting psychiatric disorders, and we found that there were worse cancer-related outcomes. Patients who had a precancer diagnosis, psychiatric hospitalization, these patients had worse cancer-specific mortality compared to those with no prior psychiatric hospitalization. You can see the hazard ratio of 1.73.

So, as we continue to move forward, not just currently, but in the coming months and possibly the coming years, as we can continue to see the outcomes of the pandemic, these considerations are going to be important. As the, at least early studies are suggesting that there's worse mental health associated just in the general community, as well as among these cancer patients.

In this cross-sectional study in Germany, 15,000 participants were assessed for mental health during COVID-19 and in the study, there's increased risk of depression, increased risk of anxiety, increased risk of distress, and overall decreased health status. And so, in their multi-variable analysis, impairment and mental health were predicted by COVID-19 fear. And as we continue to see these spikes in the pandemic, these are all going to be important factors as we counsel, not just our patients, but our colleagues as well.

So moving forward, the emergence from the COVID-19 pandemic is uncertain, certainly, in the United States, we've seen a second wave. We're starting to see that in Europe as well. And so the considerations we've discussed throughout this journal club will continue to probably be important for the coming months and possibly the coming years. And barring an efficacious vaccine, it's unlikely that the COVID-19 pandemic will completely disappear and the risk of viral transmission will continue to affect the practice of medicine.

Certainly, within the constraints of COVID-19, we need to continue to consider how to best optimize the care of patients with genitourinary cancer during these challenging times. Thank you for your attention. And we hope you found this journal club useful.