In-Hospital Venous Thromboembolism and Pulmonary Embolism After Major Urologic Cancer Surgery

We examined contemporary trends in rates of in-hospital VTE and PE in the four most frequent MUCSs (RC, RP, RN, and PN) in a population-based cohort in NIS 2010–2019. We made several important observations.

First, we identified 1180 contemporary NIS 2010–2019 patients with in-hospital VTE when all four MUCSs were examined (RC, RN, PN, RP). The risk of VTE is non-negligible after MUCS.³ It represents a life-threating complication after most cancer surgeries, including the four examined MUCSs.^8‐10 However in the current study, the presence of VTE was identified in only 1% (n = 1180) of all the patients. Moreover, we identified 583 contemporary MUCS patients (0.3%) with PE. Data addressing rates of PE without combining it with deep vein thrombosis (DVT) are limited due to the rarity of PE after MUCS.¹¹ Consequently, the current rate of PE cannot be directly compared with previous reports originating from population-based data repositories because such contemporary reports focusing on in-hospital PE rates do not exist. Therefore, population-based data repositories such as the NIS or the National Surgical Quality Improvement Program (NSQIP) are essential to study rare events associated with elevated fatality rates, especially when multivariable analyses are required.

Second, we observed a statistically significant increase in in-hospital VTE rates after MUCS (EAPC + 4.0%; p = 0.01). However, this increase was only marginal at best (from 0.6 to 0.7%) and may have no bearing in individual patient considerations. The recorded increase in in-hospital VTE rates may also suggest that more high-risk patients underwent MUCS. Indeed, the proportion of obese patients (BMI ≥30 kg/m²) increased from 8.1 to 16.3% (EAPC + 6.4%; p < 0.001). Moreover, the proportion of patients with a CCI of 3 or higher increased from 5.0 to 6.7% (EAPC + 3.6; p = 0.001). Finally, the proportion of MUCS patients age 69 years or older also increased from 23.3 to 28.1% (EAPC + 1.8%; p < 0.001). All three variables, namely, obesity (BMI ≥30 kg/m²), CCI (≥ 3), and advanced age (≥ 69 years) represent VTE risk factors.^1,12‐15 Specifically, obesity, which represents a potentially modifiable risk factor, was associated with higher risk of VTE (OR 1.3; p < 0.001) and PE (OR 1,4; p = 0.003) in the current study. Despite the consistent increase in VTE risk after MUCS, the VTE rate did not increase in a clinically meaningful fashion (from 0.6 to 0.7%). Similarly, mortality with VTE after MUCS did not increase (p = 0.8). These observations may be indicative of an improvement in quality of care over time.^16‐19 Therefore, it may be hypothesized that despite a higher patient risk profile and higher VTE rates, current VTE prevention and management strategies did not result in a mortality increase.

Third, we observed a statistically significant decrease in in-hospital PE rates after MUCS (EAPC − 4.5%; 95% CI − 6.3 to − 2.7%; p = 0.01). Although the absolute PE rate decrease was marginal at best (from 0.4 to 0.2%) and may have no bearing in individual patient considerations, a statistically significant decrease in such life-threatening complication is clearly encouraging. Consequently, as for VTE, such a decrease may be indicative of an improvement in quality of care over time, especially in light of the aforementioned increases in risk factors for VTE and vascular events in general.^16‐19

Fourth, we observed important differences in in-hospital VTE rates between the four MUCSs (RC versus RN versus PN versus RP). The rate of VTE was highest after RC (2.6%), followed by RN (1.1%), then PN (0.6%), and finally was lowest for RP (0.2%). In multivariable analyses addressing VTE rate and quantifying the magnitude of the differences between the four MUCSs, remarkably similar ORs were recorded for each of the three MUCSs that were compared with RP (OR of 4.9 for RC versus 4.5 for RN versus 3.6 for PN). This observation suggests that each of these three MUCSs (RC, RN, PN) should be considered as an equally important VTE risk factor. Consequently, RC, RN, and PN may be given virtually the same consideration in VTE strategies. The current results cannot be directly compared with previous reports because they did not focus on in-hospital VTE rates. Moreover, previous reports did not compare VTE risk after RC, RN, or PN relative to RP, which is known for its lowest VTE rate. Similarly, when PE rates were considered, remarkably similar ORs were recorded for the three MUCSs compared with RP (OR of 4.4 for RC versus 3.3 for RN versus 3.9 for PN).

Fifth, we have provided the most contemporary relative rates of mortality with VTE and PE. The specific multivariable increase in mortality with VTE was 3.7-fold for RC and 5.2-fold for RN. Similarly, the specific increase in mortality with PE was 4.9-fold for RC and 8.3-fold for RN. Unfortunately, multivariable rates could not be computed for PN and RP due to insufficient numbers of observations. The current findings cannot be directly compared with previous reports. To the best of our knowledge, we are the first to report the association between mortality and VTE in multivariable analyses for RC and RN patients.

Taken together, we observed increased rates of known VTE risk factors such as increased rates of obesity, CCI of 3 or higher, and age of 69 years or older. However, no substantial increase in VTE and PE rates and no increase in mortality with VTE or with PE were observed. Consequently, it may be postulated that VTE prevention and management strategies have improved over time. The same hypothesis may be proposed for PE. Moreover, it is also of interest to know that VTE risk was remarkably similar after RC (OR 5.1), RN (OR 4.5), and PN (OR 3.6) relative to RP, even after the most detailed multivariable adjustments. Based on these findings, clinicians should not underestimate the risk of VTE, even after RN and PN, which are considered as lower VTE risk interventions.^3,4 Finally even after most detailed multivariable adjustments, the presence of VTE increased the mortality risk after RC in fourfold fashion, and after RN in fivefold fashion. Similarly, even after the most detailed multivariable adjustments, the presence of PE increased mortality risk after RC in fivefold fashion and after RN in eightfold fashion. These observations illustrate that even in contemporary MUCS patients, whose prophylactic and therapeutic interventions are standard of care, the increase in mortality is very substantial, and assessment of VTE status and of PE status even more so is crucial. This consideration applies not only to open RC and open RN, but also to minimally invasive RC and minimally invasive RN, which may be considered a lower-risk surgical approach by some.^12,13,20,21

Despite its novelty, the current study had several limitations. First, we relied on the large-scale retrospective NIS database. All previous large-scale reports that addressed this topic also were retrospective.^12,22‐24 However, the current study relied on the most contemporary cohort (2010–2019), for which higher rates of minimally invasive MUCS, especially for RC, were observed. Second, our analyses relied on a limited number of events. Specifically, for PN and RP, multivariable analyses were not possible due to insufficient numbers of observations. Consequently, ideally even larger-scale databases than NIS could potentially provide more robust results. Third, the NIS provides exclusively in-hospital complication and mortality data. However, VTE and PE may occur after discharge. Consequently, in-hospital data may significantly underestimate true VTE and PE rates, as well as associated mortality, when the end point consists of outcomes with longer follow-up evaluation than the duration of the hospital stay.^9,21,25,26 Fourth, multivariable adjustment relied on important patient and hospital characteristics available in the NIS. It is possible that other characteristics, such as personal or family history of VTE, use of thromboprophylaxis, and tumor status may have provided a better assessment of true VTE and PE rates. However, such additional characteristics were not available in the NIS and could not be considered.

In the current study, RC, RN and PN predispose to higher VTE and PE rates than RP. Moreover, among RC and RN patients with either VTE or PE, mortality is substantially higher than among their VTE- or PE-free counterparts.