The Comprehensive Complication Index for Advanced Monitoring of Complications Following Endoscopic Surgery of the Lower Urinary Tract

Abstract

Purpose:

To evaluate the Comprehensive Complication Index (CCI) for reporting complications in lower urinary tract transurethral procedures and compare it with the Clavien–Dindo classification (CDC).

Materials and Methods:

A total of 450 consecutive patients were included into the analyses [150 each of transurethral resection of bladder tumors (TURBT), transurethral resection of the prostate (TURP), and transurethral enucleation of the prostate using Tm:YAG, (ThuLEP)]. Complications were assessed according to the modified CDC. The CCI was calculated using a freely accessible online tool. Descriptive statistics and correlation analyses were applied to quantify operational differences and length of stay (LOS) between CDC and CCI. Sample size calculations for hypothetical clinical trials were contrasted for CDC and CCI application.

Results:

Overall n = 150 patients with complications (33.3%) within the first 60 days after operation were identified. Of these, n = 125 (83.4%) were minor complications up to CDC grade IIIa. Of patients with complications, n = 57 patients (12.6%) experienced more than one complication. Here, the cumulative CCI led to an upgrade of at least one CDC grade in 33 patients. Hence, in 22.0% of cases, the highest CDC grade underestimated the degree of complications. CCI showed higher correlation with LOS compared with CDC (all r > 0.2, all p-values ≤0.0001). Using CCI instead of CDC for sample calculation resulted in a strong reduction of the required number of patients for all three interventions (percentage of patient number decrease: −93.2% for TURBT, −71.8% for TURP, and −81.1% for ThuLEP).

Conclusion:

The CCI gives a more precise interpretation of the postinterventional complications of TURBT, TURP, and ThuLEP. CCI application may reduce the required sample size for clinical trials and will relieve their recruitment in the future.

Introduction

Transurethral procedures are the most common urologic surgical interventions and the first-line options for the treatment of bladder outlet obstruction or nonmuscle invasive bladder cancer.¹ The most frequently performed interventions are transurethral resection of bladder tumors (TURBT) and transurethral resection of the prostate (TURP). Because of recent technical advances, laser operations on the prostate are becoming increasingly important, including the transurethral anatomic enucleation of the prostate using Tm:YAG (ThuLEP).² The intervention-related complications of transurethral procedures are numerous and still difficult to assess correctly because of a lack of standardization.¹

In general, complications are an unavoidable part of surgical procedures. Regardless of how well the surgeon, patient, or technical material is prepared, complications WILL occur and are often instructive for the evolution of the respective intervention.³ Thus it seems evident that, in addition to all legitimate perioperative optimization, the standardized and high-quality recording of intervention-specific complications is of great importance. This might help identify systematic errors and definitively improves patient care.⁴

The Clavien–Dindo classification (CDC) still is a widely used standard tool for assessing perioperative morbidity.⁵ Its ordinal scale rates complications from I (any deviation from the standard) to V (patient's death) and is easily applicable to all types of operation. Specific CDC modifications have been published and evaluated for their use for TURBT or TURP.^6,7 Major drawbacks, however, are the failure to compare different degrees of complication with one another and thus different surgical procedures. To give an example, the interpretation regarding the weighting of two complications of grade II with an additional CDC complication of grade III remains unclear. Nevertheless, its probably greatest disadvantage remains the considerable lack of information on all intervention-specific postoperative complications. Owing to the nature of the data collection, critical complications can hide minor but not irrelevant complications.⁸

In general operation, a CDC-based further developed score, the Comprehensive Complications Index (CCI) is considered the new reporting standard.⁹ This continuous variable includes and weights all occurred complications providing a score between 0 and 100 per patient (100 = patient's death), allowing a more detailed assessment of the intervention-related complications and a comparison between different surgical procedures. In a previous study, we validated the CCI for major uro-oncological procedures.¹⁰ However, there is no CCI assessment for transurethral procedures so far. Our goal was therefore to first introduce the CCI to endourology and evaluate whether the CCI provides a more holistic view of transurethral complications to make recommendations on replacing or maintaining the modified CDC.

Materials and Methods

Patient population

Patient data were collected retrospectively using intervention-specific databases for TURBT, TURP, and ThuLEP (institutional ethics review board approval 2020-857R-MA). The complications were assessed during the hospital stay and within 60 postoperative days. A total of 150 patients were included for each intervention, starting 60 days backdated from the start of data collection. For TURBT patients between August 16 and January 3, for TURP patients between March 5, 2019 and December 11, 2019, and for ThuLEP patients between December 13, 2018 and December 19, 2019 were considered. Patients for whom the intervention was primarily based on an indication other than subvesical obstruction (TURP, ThuLEP) or tumor resection (TURBT) were excluded from analysis. Preinterventional urine culture was obtained in all patients. In case of significant germ detection, antibiotic therapy was administered at least 24 hours before operation.

Assessment of complications

Patient-specific data and all complications that occurred were entered in an appended spreadsheet. Each patient was assigned the highest degree of complication based on the modified CDC for the respective intervention.^6,7,11 The criteria used in this study for CDC classification can be found in the supplements (Supplementary Tables S1–S3). Borderline cases were discussed by two urologists and decided by consensus. Hematuria was assessed during the inpatient stay as a direct consequence of the procedure and not as a direct complication. After inpatient discharge with clear urine, recurrent hematuria was considered a complication. All complications that occurred were CDC-equivalently listed separately. According to the EAU guidelines of reporting and grading of complications, detailed information on mortality was additionally assessed.⁴ The patient-specific cumulative complication burden was calculated using the free online CCI tool www.assesssurgery.com. Each CDC grade is assigned to a specific CCI value and a weight of complication (wC) as follows:

CDC-I	CCI score 8.66	wC1 = 300
CDC-II	CCI score 20.92	wC1 = 1750
CDC-IIIa	CCI score 26.22	wC1 = 2750
CDC-IIIb	CCI score 33.73	wC1 = 4550
CDC-IVa	CCI score 42.43	wC1 = 7200
CDC-IVb	CCI score 46.23	wC1 = 8550
CDC-V	Always results in a CCI score of 100

The total CCI score is then calculated based on the following formula: $C C I = \frac{\sqrt{w C 1 + w C 2 + w C 3 \dots + w C x}}{2} .$

Statistical analysis

For descriptive statistics, various parameters such as age, sex, American Society of Anesthesiologists (ASA) score, body mass index (BMI), and length of hospital stay (LOS) were recorded and reported in detail (mean value, min-max values, and relative and absolute rates). Bar charts and scatter plots were created for visualization purposes. Obtained complication data does not follow a normal distribution. Thus, group comparisons were carried out by nonparametric testing using Mann–Whitney U test, and correlation analyses were performed according to Spearman's rank correlation coefficient. Cause–effect relations were determined by linear regression analysis.

The CDC sample size calculation was defined assuming a relative risk reduction of 40% for the event of complications. The appropriate CCI sample size was determined using the Noether formula.¹² A power of 90% was assumed. As performed before, the effect size was defined as a deviation of 10 points on the CCI scale.⁸ The assigned standard deviations were based on the distribution in the study cohort. A two-sided alpha level of 5% was tolerated for all analyses. Statistical analyses were performed with JMP^® software (version 14.0.0; SAS Institute, Cary, NC).

Results

Overall 450 patients, 150 for each transurethral intervention, were included. Patient characteristics are given in Table 1. The median age for all three interventions was 71.2 years. In the TURBT, 81.3% of patients were men. The median BMI was 26.7 kg/m² and the median LOS was 4.0 days. About 83.7% of patients were classified into ASA group I or II.

Table 1.

Baseline Characteristics of Included Patients

	Year	No. of patients	Age (years)^a	Gender (male)^b	ASA [1–4]^b	BMI (kg/m²)^a	Length of stay^a
TURBT	2019–2020	150	73.0 (44.0–94.5)	150 (81.3)	[1] 13 (8.9)	27.0 (17.4–54.1)	4.2 (2.0–51.0)
					[2] 72 (49.3)
					[3] 60 (41.1)
					[4] 1 (0.7)
					[1] 19 (14.4)
TURP	2019	150	70.7 (51.2–89.3)	150 (100)	[2] 76 (57.6)	26.3 (18.6–37.6)	4.0 (2.0–14.0)
					[3] 34 (25.8)
					[4] 3 (2.2)
					[1] 34 (22.7)
ThuLEP	2018–2020	150	70.0 (49.0–87.0)	150 (100)	[2] 87 (58.0)	26.9 (16.1–40.3)	3.8 (2.0–17.0)
					[3] 29 (19.3)
					[4] -

Values are given as mean (range) if not indicated otherwise.

Values are reported as n (%) if not indicated otherwise.

ASA = American Society of Anesthesiologists; BMI = body mass index; ThuLEP = Transurethral Anatomic Enucleation of the Prostate using Tm:YAG; TURBT = transurethral resection of bladder tumors; TURP = transurethral resection of the prostate.

Number and extent of complications

The total number of complications, their distribution according to CDC grades, and the number of patients with more than one complication are given in Figure 1. In total n = 150 (33.3%) of patients suffered from complications. At least one complication occurred in n = 30 (20.0%) patients after TURBT, in n = 67 (44.7%) patients after TURP, and in n = 53 (35.4%) patients after ThuLEP. Of those n = 125 (83.4%) were minor complications up to CDC grade IIIa. In each type of intervention, grade I complications were the most common (overall n = 56, 37.4%). CDC grade IIIb complications were noticed in n = 4 (2.6%) for TURBT, in n = 5 (3.4%) for TURP, and in n = 13 (8.6%) for ThuLEP. In all interventions, a complication of CDC grade IV (n = 1, 0.7% each) was detected, which was also the most serious complication. In TURBT, one patient showed bradycardia necessitating emergency intervention, in TURP one patient suffered a myocardial infarction, and in ThuLEP one patient had a hemorrhagic shock.

FIG. 1.

(A) CDC-rated complications for each intervention. The overall most common complication that occurred first was hematuria. (B) Number of complications that occurred. Additional information was obtained for 57 (12.7%) patients. CDC = Clavien–Dindo Classification; ThuLEP = Transurethral Anatomic Enucleation of the Prostate using Tm:YAG; TURBT = transurethral resection of bladder tumors; TURP = transurethral resection of the prostate; UTI = urinary tract infection.

More than one complication occurred in 10 (6.7%) patients with TURBT, in 30 (20.0%) patients with TURP, and 17 (11.4%) patients with ThuLEP. The most frequent complications were hematuria (n = 43, 28.7%), urinary retention (n = 39, 26.0%), and urinary tract infection (UTI, n = 29, 19.4%). Twenty-two patients (4.9%) had to undergo a complication-related procedure under general anesthesia. There was no TUR-syndrome, multiorgan dysfunction, or intervention-related death to report.

Performance of CCI compared with CDC

Figure 2 provides the added value of implementing the CCI instead of the CDC. To enable a direct comparison, we converted the CDC into a so-called highest CCI (hCCI), where we transformed the highest CDC degree into the corresponding CCI value (see CCI score above). For better comprehensibility the actual CCI is called cumulative CCI (cCCI). The CCI added value can be indicated as the area under the curve between the red cCCI curve and the gray-scaled bar chart. In all patients who suffered a complication, additional information was obtained by the cCCI in 38.0% of patients. If one takes the respective value of the cCCI and then reconverts it to CDC based on hCCI values, in total 33 (22.0%) patients with complications must be classified in a higher CDC category. Or in other words, in 22.0% of all complications, applying the highest CDC grade underestimated the degree of complications. For TURBT, 7 patients (4.7%), for TURP, 17 patients (11.4%), and for ThuLEP, 9 patients (6.0%) would have to be assigned at least one CDC degree higher.

FIG. 2.

Illustration of the additional information delivered by cCCI in comparison with hCCI. The graphic bars show the cCCI, the white scaled area under the red curve represents the missing information. The respective hCCI values for the different interventions are color coded. CCI = comprehensive complication index; cCCI = cumulative CCI; hCCI = highest CCI.

Correlation of complications with the LOS

Cohort analysis showed no correlation of both complications scores with age, gender, ASA score, or BMI (all r ≤ 0.3, all p > 0.05). However, as given in Figure 3, LOS correlated significantly with CDC ( = hCCI) (TURP: r = 0.36, p < 0.01; ThuLEP: r = 0.42, p < 0.01) and cCCI (TURP: r = 0.36, p < 0.01; ThuLEP: r = 0.43, p < 0.01) for TUR-P and ThuLEP. No correlation could be found for TURBT (hCCI TURBT: r = 0.20, p = 0.02 vs cCCI TURBT: r = 0.20, p = 0.02). Thereby cCCI shows a slightly higher prediction for the LOS than the hCCI for TURP (cCCI-R ² = 0.15 vs h-R ² = 0.14) and ThuLEP (cCCI-R ² = 0.21 vs h-R ² = 0.20).

FIG. 3.

Comparison of the correlation rates of cCCI and hCCI with LOS shows higher correlation with cCCI for all three interventions (p < 0.0001). LOS = length of stay.

Sample size calculation

To simulate the effect of CCI application in a fictive clinical trial with postoperative complications as primary endpoint, we assumed parameters as indicated in Figure 3. The sample calculation showed for each intervention a considerable reduction in the number of patients required because of the use of CCI (Table 2). There was a notional sample size reduction of −93.2% for TUR-B (n = 440 vs n = 30), −71.8% (n = 149 vs n = 42) for TUR-P, and −81.1% (n = 212 vs n = 40) for ThuLEP after application of the CCI instead of the CDC.

Table 2.

Fictive Sample Size Calculation Showed CCI-Related Strong Reduction in Required Samples (−93.2% for TURBT, −71.8% for TURP, and −81.1% for ThuLEP)

Procedure	Cohort	Assumption	Sample size (per group)
TURBT
No. of patients with CDC complications	30/150 = 20%	40% relative risk reduction	437
Mean CCI ± SD	4.5 ± 10.8	Δ 10	26
TUR-P
No. of patients with CDC complications	67/150 = 44.7%	40% relative risk reduction	146
Mean CCI ± SD	9.5 ± 13.1	Δ 10	37
ThuLEP
No. of patients with CDC complications	53/150 = 35.3%	40% relative risk reduction	209
Mean CCI ± SD	7.9 ± 12.8	Δ 10	36

CCI = Comprehensive Complication Index; CDC = Clavien–Dindo Classification; SD = standard deviation.

Discussion

The structured and standardized recording of intervention-related complications is essential for the evaluation of the respective surgical technique, the surgeons, and also for the recording of systematic errors.⁴ The delicate field of error culture requires a maximum of transparency, acceptance, and applicability. Valid and intuitive tools are necessary for achieving this. The currently most frequently used classification in urology is the CDC.⁵ The modified CDC is a step forward to a standardized assessment of endourologic complications.⁶ However, in addition to its nominal value, the CDC offers further obvious weaknesses. In transurethral procedures, for example, a pigtail insert in analgosedation (IIIb) is rated higher than a much more invasive nephrostomy or cystostomy insertion (IIIa).⁷ In addition, a comparison of different studies often reveals considerable flexibility in the interpretation of the respective degree of complications.^6,11

Moreover, because of the lack of a continuous variable, the CDC does not allow direct comparisons between interventions or the calculation of complicative mean values. Thus, the CDC and consequently the interventional complications often remain as foreign bodies in the overall statistical analysis of clinical trials, although they should be outlined as key aspects.

A further development of the CDC, the CCI could help here and allow a more integrative assessment of the complications. First introduced in general operation and validated for different surgical procedures, it can now be considered as standard tool for many surgical trials.^8,13 In urology, the CCI has only been described twice, retrospectively in cohorts in open urologic procedure.^10,14 It has not yet been reported in endourology. The ability of the CCI to cumulatively record several complications per patient and weight them on a continuous scale allows a holistic representation of every single complication that occurred.

This is all the more true for generally high complicative interventions such as transurethral endoscopic operations.¹ In our cohort 33.4% of patients suffered from complications. The main complications were hematuria, urinary retention, and UTI. These findings and the rate of complications that occurred are in line with previous studies in the field.^1,7,15 The complication rate of TURBT was low compared with the prostatic interventions. The TURP was the intervention with the most complications. Overall, minor complications were the most common with 83.4%. ThuLEP had the most frequent IIIb complications. This is because of the fact that these patients most frequently required tamponade removal or vaporization under anesthesia.

In general, complications in endourology are low grade and rarely dangerous to the patient.¹ Nevertheless, a standardized recording is necessary yet also a challenge.⁶ The example of hematuria, the management of which can range from increased diuresis, bladder irrigation, to renewed surgical intervention, shows the range of possible CDC degrees for single type of complications. Especially in endourologic interventions, the intervention-specific complications are often conditional. For example, a UTI first leads to urinary retention and then to hematuria. This might explain the high rate of multiple complications in one patient and underlines the need to record and evaluate all complications in transurethral interventions.

In this study, the CCI was able to provide more information in 38.0% of patients with complications and shifted the CDC grade in 22.0% of patients with complications, a fact that has also been seen in open urologic operation.¹⁰ This additional gain in information led the first authors of the CDC around Clavien, to recommend the recording of all complications and thus the use of the CCI.⁹ In times of centralization of uro-oncological operations in large-volume hospitals, the CCI could play an important role in the illustration of the impact of the respective surgeons¹⁶ and the required amount of operations.¹⁷ Another advantage of the CCI we could demonstrate in this study is its use to reduce cohort size in clinical trials. Thanks to the weighted detection of the complications and thus their more sensitive presentation, the sample sizes can be downsized compared with the dichotomized, CDC-based calculations. Similar findings have already been described for open urologic procedure and pancreatic procedure.^8,10

Limitations

A major limitation of the study is the retrospective study design, which might lead to an underestimation of the true number of complications owing to a potential number of not reported minor complications. Because we have not collected any external data on outpatient follow-up care, we may have missed complications here as well. However, as described previously, this leads to an underestimation of the true number of complications. When assessing complications in a prospective manner, more complications will be detected. In such a case, the CCI will be even more valuable to capture the cumulative burden of complications. Our complication rates are also consistent with published data on endourologic complication rates.¹ Another limitation is the cohort size. This does not allow a general transfer to endourologic interventions yet. Nevertheless, even with the small number of patients, this study could already demonstrate a strong additional benefit of CCI. A more detailed assessment of the benefit of CCI in transurethral interventions will be available in future prospective endourologic studies.

Conclusion

This study introduces and validates the CCI for transurethral procedures on a retrospective patient cohort of a tertiary center. We could demonstrate that the CCI is able to capture the cumulative burden of postoperative complications for a single patient and that it provides better prediction of the LOS compared with the CDC. In addition, we were able to show that the use of CCI might help reducing sample size in upcoming clinical trials in endourology. In summary, we recommend the use of the CCI for recording postoperative complications in endourology.

Footnotes

Authors' Contributions

F.W.: project development, data collection, figure and article drafting; M.N.: data collection, statistical evaluation, figure and manuscript drafting; K.F.K.: project development, statistical guidance and article sketching; B.G.: data collection; J.v.H.: data collection, project supervision; P.N.: data collection, project supervision; M.S.M.: project supervision; M.C.K.: project development, supervision and article editing.

Compliance with Ethical Standards

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

Supplementary Material

Supplementary Table S1

Supplementary Table S2

Supplementary Table S3

Abbreviations Used

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