Oncology

The COVID-19 Pandemic: Implications for Triaging and Managing Patients with Genitourinary Malignancies

Over the last several months, the diagnosis, treatment and surveillance of genitourinary malignancies has been transformed by the global COVID-19 pandemic. The heavy demand for resources, exacerbated by limited excess health system capacity, means that health care systems have become quickly overwhelmed and hospitals have become sources for virus transmission. Furthermore, a severe COVID-19 phenotype is seen more commonly in men and older, more comorbid patients. Indeed, this is the same comorbidity profile common for patients with genitourinary malignancies. Early results from the Lombardy region of Italy showed that among 1,591 patients admitted to the ICU, the median age was 63 years (IQR 56-70) and 82% were male. Among these patients, the mortality rate was 26%, which is likely to increase with additional follow-up.

As clinicians, it is important to be good stewards of resources, patient safety and community health initiatives, but at the same time prioritize oncology patients for whom delays in treatment may result in harm. In the absence of data, guidance of care relies on expert opinion, including a collaborative review published April 21, 2020 in European Urology (Wallis CJD, Klaassen Z, et al). As follows is a summary of the statements provided, stratified by disease site, about providing recommendations as to who can safely defer treatment until after the pandemic is over versus those that should be treated immediately.

It is safe to defer cystoscopic surveillance and transurethral resection of bladder tumors (TURBT) for recurrence in patients with known low-grade non-muscle invasive bladder cancer (NMIBC) tumors during the COVID-19 pandemic. Patients presenting with new symptoms, such as the onset of visible hematuria, should be re-evaluated. In patients with high-grade NMIBC, induction BCG and one course of maintenance therapy should be offered as first line therapy. Re-resection may be deferred in lower risk cases (e.g. pTa), but should not be abandoned in higher stage (pT1) or higher risk disease, especially if no muscle was present in the initial resection. Radical cystectomy (RC) should be offered for higher risk tumors, if hospital capacity allows and if patient co-morbidities do not put them at higher post-operative risk. Delays to RC of up to 12 weeks may be safe for muscle-invasive bladder cancer (MIBC). Neoadjuvant chemotherapy should be considered where feasible, with due attention to the risk of immunosuppression weighed against the benefit. Additionally, radiotherapy (trimodal therapy with radio-sensitizing chemotherapy) could be considered as an alternative based on individual hospital and patient factors. First-line treatment should be commenced when possible for metastatic urothelial carcinoma and should not be stopped without justification. Immunotherapy rather than chemotherapy may be given preferentially to patients with PD-L1 positive tumors. During the COVID-19 pandemic, risks and benefits of systemic therapy should be considered on an individual level, taking into account disease characteristics (i.e. PD-L1 positivity), tumor load and dynamics, patient performance status, geographical COVID-19 burden, and hospital resources.

Active surveillance should be the preferred management strategy for patients with low-risk prostate cancer (PCa). Patients considering focal therapy may safely defer treatment until the pandemic is over. For patients with intermediate and high-risk disease, delays of 3 to 6 months appear not to be associated with adverse pathologic outcomes, biochemical recurrence, or survival outcomes. Some data suggests that these intervals may be longer (up to 12 months in patients with high-risk disease). Neoadjuvant androgen deprivation therapy (ADT) prior to radiotherapy is standard of care usually for 2-3 months. It might be prolonged much longer for those at particularly high risk of progression or recurrence, if radiotherapy has to be delayed until after peak health care resource utilization associated with COVID-19. For surgery, although added value of neoadjuvant ADT is questionable, it might also be considered if a patient is interested in such an approach. Men starting radiotherapy can safely defer treatment for 3-6 months. Hypofractionation (either moderate, 19-20 fractions over 3.8-4 weeks, or extreme, 5-7 fractions, an SBRT approach) may decrease health care burden and patient coronavirus exposure. Patients with metastatic PCa should commence treatment, prioritizing androgen receptor-targeted therapies over chemotherapy. Glucocorticoid use should be minimized and patients should be considered for longer duration ADT injections.

Surveillance of small renal masses (SRMs) is safe. When treatment is necessary (i.e. SRM growth over time), it should be delayed under the current circumstances. Though there are fewer data in T1b and T2 disease, delays of 3 to 6 months do not appear to adversely affect outcomes. The data is scant regarding the safety of delaying surgery in patients with ≥cT3 renal masses, in particular those with renal vein or IVC tumor thrombus involvement. These patients should be prioritized for surgical intervention given the locally advanced nature of their disease, unknown risk of delayed resection, and potential for significant symptomatic complications including bleeding and IVC occlusion. In the current landscape, upfront systemic therapy should be prioritized over cytoreductive nephrectomy in asymptomatic patients with metastatic kidney cancer. Nephrectomy should be reserved for symptomatic patients. Patients with treatment-naïve favorable and intermediate -risk disease who are asymptomatic or minimally symptomatic with limited disease burden, may be considered for active surveillance until disease progression during the COVID-19 pandemic. For poor risk patients and those requiring treatment, there is no consensus to the optimal first line therapy, however VEGF targeted therapy is less likely to require toxicity-related hospitalization and/or glucocorticoids than immunotherapy regimens.

Patients with suspected upper tract urothelial carcinoma (UTUC) may be initially investigation with urine cytology and CT urogram, forgoing diagnostic ureteroscopy unless there is considerable diagnostic uncertainty. Patients with low-grade UTUC are often managed with nephron-sparing approaches and thus are likely to have minimal to no risk with a surgical delay. In patients with high-grade disease, delays up to 12 weeks may not be associated with changes in survival, despite worse pathological outcomes.

Guidelines and expert opinion recommend avoiding surgical delays for radical orchiectomy. The burden on the healthcare system is likely minimal, as these operations are short and routinely performed in a same-day surgical setting. Surveillance should be the preferred option for most patients with Clinical Stage I disease. There are insufficient data to provide guidance on the effects of delaying post-chemotherapy RPLND. Patients with intermediate and poor prognosis metastatic germ cell tumors should receive chemotherapy immediately.

There are no studies assessing the risk of delayed intervention of primary penile carcinoma, however given the rarity of this malignancy, symptomatology, and high risk for metastatic progression, it seems reasonable to avoid delays in primary surgical treatment. Additionally, inguinal lymphadenectomy for men with clinic pathologic indications should occur within three months of treating the primary lesion.

Without question, there is a significant psychological burden associated with a cancer diagnosis, likely magnified by delays in treatment. Furthermore, physicians who treat cancer patients must be good stewards of limited health care resources, particularly in times of a pandemic. As a result, it is important to prioritize the timely care of patients for whom delays are most likely to result in adverse outcomes, also taking into account the patient’s age, comorbidities, symptoms, and life expectancy.