key: cord-0980859-6ns7r8r5
authors: Ginsburg, Kevin B.; Curtis, Gannon L.; Patel, Devin N.; Chen, Wen Min; Strother, Marshall; Kutikov, Alexander; Derweesh, Ithaar H.; Cher, Michael L.
title: Association of Surgical Delay and Overall Survival in Patients with T2 Renal Masses: Implications for Critical Clinical Decision-Making during the COVID-19 Pandemic
date: 2020-09-20
journal: Urology
DOI: 10.1016/j.urology.2020.09.010
sha: 80fabef4b4c97fc757c407e87504d3bd19c5882d
doc_id: 980859
cord_uid: 6ns7r8r5

OBJECTIVE: To test for an association between surgical delay and overall survival (OS) for patients with T2 renal masses. Many health care systems are balancing resources to manage the current COVID-19 pandemic resulting in surgical delay in patients with large renal masses. METHODS: Using Cox proportional hazard models, we analyzed data from the National Cancer Database for patients undergoing extirpative surgery for clinical T2N0M0 renal masses between 2004 and 2015. Study outcomes were to assess for an association between surgical delay with overall survival and pathologic stage. RESULTS: We identified 11,848 patients who underwent extirpative surgery for clinical T2 renal masses. Compared with patients undergoing surgery within 2 months of diagnosis, we found worse OS for patients with a surgical delay of 3-4 months (HR 1.12, 95% CI 1.00-1.25) or 5-6 months (HR 1.51, 95% CI 1.19-1.91). Considering only healthy patients with CCI=0, worse OS was associated with surgical delay of 5-6 months (HR 1.68, 95% CI 1.21-2.34, p=0.002) but not 3-4 months (HR 1.08, 95% CI 0.93-1.26, p=0.309). Pathologic stage (pT or pN) was not associated with surgical delay. CONCLUSIONS: Prolonged surgical delay (5-6 months) for patients with T2 renal tumors appears to have a negative impact on OS while shorter surgical delay (3-4 months) was not associated with worse OS in healthy patients. The data presented in this study may help patients and providers to weigh the risk of surgical delay vs. the risk of iatrogenic SARS-CoV-2 exposure during resurgent waves COVID-19 pandemic.

The current COVID-19 pandemic has disrupted systems of care. In these turbulent times, triage of clinical care delivery and appropriate calibration of care intensity have taken center stage. Oncology providers, in particular, are challenged to balance the risks of cancer progression vs. the risks of COVID-19 morbidity and mortality, while potentially being constrained by limited healthcare resources 1 . In patients with localized kidney cancer for whom surgery presents an opportunity for oncologic cure, nuanced clinical decision-making is particularly critical.

Active surveillance for the small renal mass (< 4 cm in size) is a well-established and safe management strategy [2] [3] [4] [5] [6] . Although larger renal tumors are known to harbor higher oncologic risks, it remains unclear to what extent if any, that a short to intermediate term delay in time to definitive management may impact survival. Prior studies on larger renal masses are limited by relatively small numbers from single institutions [7] [8] [9] or describe pre-selected patients who were poor surgical candidates [10] [11] [12] [13] [14] [15] .

There is a paucity of literature evaluating the impact of surgical delay on survival in the setting of large renal masses in contemporary patient cohorts.

In the setting of ongoing resource limitations and the risk of iatrogenic exposure of patients and providers to SARS-CoV-2, the decision to proceed with surgery for large renal masses pivots on the ability to assess the risk of surgical delay. As such, additional data are needed to guide these decisions. 20 . A sensitivity analysis was performed with OS calculated as the interval from diagnosis to death or last clinical contact. Due to concern that comorbidity may be related to OS and surgical delay, a subgroup analysis was performed of patients with a comorbidity score of 0. Secondary outcomes of interest were to test for an association between surgical delay and upgrading to pathologic T3/4 disease or node positive (pN+)

in patients who underwent a lymphadenectomy.

The 

The Kaplan-Meier curves of unadjusted overall survival for men different categories of surgical delay are shown in in Figure 1A . There were 2,806 deaths during follow up. In the multivariable Cox proportional hazards model, we detected a significant association between surgical delay and overall survival ( 

Lastly, we did not observe a significant association between surgical delay and upgrading or pN+ disease. Similar odds of upgrading and pN+ disease was seen in patients treated 3-4 and 5-6 months after diagnosis compared with patients treated within 2 months of diagnosis (Table 3) .

As resurgent waves of the COVID-19 pandemic continues to strain hospital systems' resources and personnel, non-emergent surgeries are being delayed 21 . The goal of this study was to assess the association of surgical delay with OS in patients with large renal masses. To this end, we report that patients with cT2 renal masses who experienced prolonged delays in surgical treatment of their cancer exhibited decreased OS when compared to patients who underwent surgery soon after diagnosis. A similar association was seen when we restricted the cohort to patients with a comorbidity index of 0, while shorter surgical delay (3-4 months) was not associated with worse OS in healthy patients. We did not observe a significant association of surgical delay and intermediate outcomes of pathologic upgrading and pN+ disease.

The implications of treatment delay for patients with cancer is deservedly on many patients' and clinicians' minds during these uncertain times [22] [23] [24] 26, 27 . These studies included patients with renal masses of all sizes and demonstrated an association between prolonged treatment delay and overall survival. In both studies, the median time to surgery was less than one week, suggesting possible inaccuracies in the recording of surgical delay.

Indeed, a strength of our study was the inclusion only of patients in which surgical delay could be accurately characterized.

Our work continues to build upon the limited data regarding surgical delay in patients with cT2 renal masses by utilizing a large, contemporary, nationally representative cohort to suggest a small, but significant, absolute difference in overall survival in patients with prolonged surgical delay. We did not observe a significant difference in intermediate outcomes of pathologic upgrading and pN+ disease with treatment delay. Furthermore, when restricting the analysis to healthy patients with CCI, a short delay was not associated with worse OS. These data suggest that a short treatment delay due to the COVID pandemic may not affect survival nor worsen oncological outcomes of upgrading or node positivity. During the ongoing COVID-19

pandemic, the harms of surgical delay must be carefully weighed against multiple other considerations, including the risk of iatrogenic exposure to the virus, the compromise of social distancing during care delivery, and allocation of limited health resources 1 . This calculus must be individualized, informed by accurate estimates of the risks involved, and include active patient participation when deciding on the optimal timing of surgery.

Furthermore, as the current pandemic resolves, these data may provide reassurance to patients which require a short delay to allow for medical maximization and improved control of chronic medical conditions prior to proceeding with surgery.

This study had several limitations. First, although we attempted to adjust for confounding variables in our multivariable models, no statistical adjustment of data obtained from pre-selected cohorts can fully account for both measured and unmeasured confounders. Granular details regarding specific comorbidities or oncologic characteristics, such as imaging findings or the health of the contralateral kidney, are not available in the NCDB. Second, the cause for delay in surgeries is unknown and the generalizability of these results to patients who have deferred surgery during the COVID-19 pandemic remains unclear. It remains possible that generally sicker and unhealthier patients may take longer to proceed to surgery due to more intense surgical clearance and medical optimization processes. Lastly, this study was limited by the variables collected by the NCDB. Oncologic outcomes such as disease recurrence, progression, and cancer specific mortality were not available. Despite these limitations, this study uses current data from a national database with a large cohort providing a level of power that is not present in the current literature. 

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