Surgical Delays Caused By COVID-19 Do Not Increase Risk of pT3a Upstaging, Compromise OS in cT1b-cT2b RCC

The coronavirus disease 2019 (COVID-19) pandemic has led to delays in elective and potentially curative surgeries for patients with cT1b-cT2b renal cell carcinoma (RCC) but research has indicated that surgical delays of up to and beyond 3 months did not result in an increased risk of pT3a upstaging or comprise overall survival (OS), Arnav Srivastava, MD, said in a presentation during the 2020 Virtual International Kidney Cancer Symposium.¹

Results demonstrated that patients with cT1b tumors who had their surgery delayed for less than 1 month after diagnosis had a 8.9% upstaging rate, those who were delayed for 1-3 months had a 9.3% upstaging rate, and those who were delayed beyond 3 months had an upstaging rate of 9.1%. Patients with cT2a tumors had upstaging rates of 24.9%, 23.8%, and 24.5% when they experienced surgical delays of less than 1 month, 1-3 months, and over 3 months following diagnosis, respectively. Finally, patients with cT2b tumors experienced the highest upstaging rates, at 33.1%, 30.1%, and 35.6%, respectively for each delay time point.

“We further studied this using a multivariable logistical regression [analysis] and really came to the same conclusion,” said Srivastava, who is a senior resident within the Division of Urology at Rutgers Robert Wood Johnson Medical School. “At this time, we feel pretty comfortable saying that there is no clear association between surgical delay up to 3 months and pT3a upstaging. The sensitivity analysis also confirmed this.”

Results from the OS analysis proved to yield similar findings. An association between surgical delay and worse OS was not observed in patients with cT2a and cT2b tumors, according to Srivastava. However, a slight association was noted in cT1b tumors; patients who had surgery more than 3 months after diagnosis seemed to have slightly worse outcomes compared with those who underwent surgery more rapidly.

“The closer we looked at this, we came to the conclusion that this was likely a more spurious finding,” Srivastava explained. “We had a couple reasons to believe so. Number 1, we saw no association with pT3a upstaging and surgical delays among cT1b tumors. Number 2, we saw no association with surgical delay and pT3a upstaging or OS among cT2 tumors. This is likely a finding that is stooped in the impact of unmeasured confounders, patient comorbidities, and the difficulty that some patients may have in coordinating their care.”

The inspiration for the study came in light of the widespread changes that have been observed in the healthcare industry in light of the COVID-19 pandemic. These changes most prominently manifested in the delay of surgeries, according to Srivastava, many of which were non-emergent, but potentially curative. The rationale for this was that various resources such personal protection equipment and ventilators needed to be preserved and healthcare systems wanted to prevent the spread of the virus to those who would need to stay in the hospital following such a procedure.

"When we start to think about the effects of delaying partial or radical nephrectomy for localized kidney cancer, studies started to come out to quantify and give recommendations as to how we should approach these patients,” said Srivastava. “[One paper stated] that most cT1 masses can likely be safely delayed, but the data get murkier for masses that were T1b or greater. This was really due to a paucity of information at the time.”²

A subsequent review that was conducted by investigators at Rutgers Robert Wood Johnson Medical School attempted to collect some recommendations based on previously published papers but yielded mixed advice.³

"Some [recommendations] said that you should not delay surgeries for larger tumors, while others said that delays were likely safe,” Srivastava noted. “As a result of these mixed recommendations, different institutions had diverse policies on how they approached these patients with localized kidney cancer.”

After reviewing the information available and starting the project, Srivastava and colleagues theorized that patients with T1a tumors are likely safe to delay surgery based on active surveillance literature for small renal masses. In contrast, patients with tumors that are T3a or greater typically have a more aggressive biology; therefore, nephrectomy should not be delayed in these cases. However, it's largely unknown how surgery delays will affect patients with T1b-T2b tumors. “We wanted to answer this question with our study,” said Srivastava.

Investigators set out to assess the risk of pT3a upstaging in patients with cT1b-cT2b RCC tumors by clinical stage and surgical delay and to evaluate the impact of surgical delay on OS within this patient population. In order to accomplish this, investigators utilized data from the National Cancer Database (NCDB). Patients who were on active surveillance, those who underwent percutaneous ablation of their tumor, or those who were not undergoing surgery, were excluded from the analysis. Patients with missing stage or histology data were also not included. Surgical delay was defined as time from diagnosis to surgery.

The primary end point of the study was pT3a upstaging after radical or partial nephrectomy with OS as the key secondary end point.

The study was not without limitations, according to Srivastava. Although the NCDB is a very useful tool, Srivastava said that it is still a retrospective administrative database. “As such, we unfortunately do not have the data granularity that one might expect from an institutional database,” he added.

Additionally, data pertaining to cancer-specific survival, recurrence-free survival, or tumor growth rates were not available. The surgical delay cutoffs were based on institutional experience; as such, it’s possible that if the cut points are changed as to defining what constitutes delayed surgery versus immediate surgery, Srivastava said, it may result in different associations with survival and surgical delay.

“For the majority of these patients, surgical delays of up to 3 months and possibly beyond do not seem to compromise survival,” Srivastava concluded. “However, when we triage these patients, we have to be very careful to incorporate the patient characteristics, the tumor characteristics, and the overall stability of the healthcare system at the time. Those are the keys to ensuring we optimize our patient care and help navigate the new challenges in healthcare with the COVID-19.”

References

1. Srivastava A, Patel HV, Kim S, et al. Delaying surgery for clinical T1b-T2bN0M0 renal cell carcinoma: oncologic implications in the COVID-19 era and beyond. Presented at: 2020 Virtual International Kidney Cancer Symposium; November 6-7, 2020; Virtual. Accessed November 9, 2020.
2. Stensland KD, Morgan TM, Moinzadeh A, et al. Considerations in the triage of urologic surgeries during the COVID-19 pandemic. Eur Urol. 2020;77(6):663-666. doi:10.1016/j.eururo.2020.03.027
3. Shinder BM, Patel HV, Sterling J, et al. Urologic oncology surgery during COVID-19: a rapid review of current triage guidance documents. Urol Oncol. 2020;38(7):609-614. doi:10.1016/j.urolonc.2020.05.017