Study overview

We assessed whether exophytic percentage (EP) and intrarenal tumor burden (ITB) add information about pathologic aggressiveness beyond tumor size.

Statistical analysis

EP = 100 × exophytic/(exophytic + endophytic) volume; ITB = endophytic/healthy volume. Healthy volume excludes tumor and refers to the affected kidney; ITB can exceed 1. Ratios assume a common voxel grid; interpolation validity was not assessed. Analyses include the six investigator-selected histologies in Table 1 and all five outcomes in Table 2. High grade (ISUP 3–4 vs. 1–2) is restricted to clear-cell/papillary RCC; advanced stage is T-stage ≥2 versus T1. Each outcome uses complete cases, excluding missing/nonapplicable findings. Separate Firth logistic models evaluate EP per 10 percentage points and ITB per doubling, adjusting for log2(size). We report odds ratios (ORs), approximate Wald 95% confidence intervals (CIs), and nominal two-sided P values. All analyses are exploratory. Marker AUCs use DeLong CIs. Added predictive value compares size alone with size plus EP or ITB, correcting AUC and Brier scores for optimism with 200 bootstrap samples. P values < 0.05 are considered statistically significant. All analyses were performed in R 4.4.1 (R Core Team, Vienna, Austria).

Results

Cohort

The six selected histologies include 411 of 489 tumors; 2 lacked size. One included multilocular cystic RCC (case_00403) is coded nonmalignant; its inclusion follows histology and the malignancy coding requires review. Outcome-specific sample sizes appear in Table 2.

Characteristic	Median (IQR) or n (%)	Missing, n
Table 1. Characteristics of included tumors
Continuous measures
Age at procedure (years)	60.0 (51.0-68.0)	0
Radiographic size (cm)	4.0 (2.6-6.3)	2
EP (%)	42.6 (22.0-64.2)	0
ITB (ratio)	0.08 (0.03-0.23)	0
Gender
Male	264 (64.2%)	—
Female	146 (35.5%)	—
Transgender (male to female)	1 (0.2%)	—
Histology
Clear-cell RCC	310 (75.4%)	—
Papillary RCC	45 (10.9%)	—
Chromophobe RCC	38 (9.2%)	—
Clear-cell papillary	12 (2.9%)	—
Unclassified RCC	4 (1.0%)	—
Multilocular cystic RCC	2 (0.5%)	—
Included cohort: N = 411.

Values are median (IQR) or n (%). Age uses the supplied age-at-nephrectomy field.

Outcome	Eligible	Outcome data			Analysis sample
Table 2. Outcome availability and analysis samples
Outcome	Eligible	Available	Positive	Missing	N	Positive
High grade (3-4)	355	352	138	3	350	137
Necrosis	411	407	98	4	405	97
T-stage >=2	411	406	137	5	404	136
Sarcomatoid features	411	406	26	5	404	26
Rhabdoid features	411	406	13	5	404	13

Model counts additionally require complete predictors. Histology restrictions account for some differences from the abstract’s denominators.

Relationship with size

Spearman correlations with size were 0.36 for EP and 0.87 for ITB.

Figure 1: EP and ITB versus tumor size, with linear fits and 95% confidence bands.

Unadjusted discrimination

Outcome	N	AUC (95% CI)
Table 3. Unadjusted discrimination
Outcome	N	Tumor size	EP	ITB
High grade (3-4)	350	0.74 (0.69-0.80)	0.63 (0.57-0.69)	0.73 (0.67-0.79)
Necrosis	405	0.81 (0.77-0.86)	0.63 (0.57-0.70)	0.78 (0.73-0.83)
T-stage >=2	404	0.90 (0.86-0.94)	0.65 (0.59-0.71)	0.87 (0.83-0.91)
Sarcomatoid features	404	0.84 (0.77-0.91)	0.73 (0.62-0.84)	0.77 (0.68-0.87)
Rhabdoid features	404	0.81 (0.70-0.92)	0.61 (0.42-0.80)	0.77 (0.67-0.88)

Higher marker values predict positive findings. T-stage partly incorporates size, so its association with size is partly definitional.

Size-adjusted associations

Predictor / increment	OR (95% CI)		P value
Table 4. Associations with pathologic findings
Predictor / increment	Unadjusted	Size-adjusted	P value
High grade (3-4)
EP: per 10 percentage points	1.19 (1.09-1.29)	1.07 (0.97-1.18)	0.187
ITB: per doubling	1.52 (1.34-1.72)	1.11 (0.90-1.36)	0.338
Necrosis
EP: per 10 percentage points	1.21 (1.10-1.32)	1.04 (0.94-1.15)	0.467
ITB: per doubling	1.59 (1.40-1.81)	0.90 (0.72-1.13)	0.374
T-stage >=2
EP: per 10 percentage points	1.22 (1.13-1.33)	0.99 (0.88-1.12)	0.912
ITB: per doubling	2.51 (2.08-3.02)	1.26 (0.95-1.66)	0.103
Sarcomatoid features
EP: per 10 percentage points	1.40 (1.18-1.67)	1.18 (0.99-1.40)	0.066
ITB: per doubling	1.49 (1.24-1.78)	0.77 (0.56-1.06)	0.106
Rhabdoid features
EP: per 10 percentage points	1.18 (0.96-1.45)	0.99 (0.81-1.22)	0.933
ITB: per doubling	1.47 (1.15-1.87)	0.87 (0.57-1.31)	0.502
P values are from size-adjusted models.

Adjusted models include log2(size) plus either EP or log2(ITB).

Added predictive value

Outcome	Size alone	Size + EP (change)	Size + ITB (change)
Table 5. Added predictive value beyond tumor size
High grade (3-4)	0.741	0.740 (-0.001)	0.742 (+0.001)
Necrosis	0.816	0.814 (-0.003)	0.814 (-0.002)
T-stage >=2	0.898	0.896 (-0.001)	0.897 (-0.001)
Sarcomatoid features	0.837	0.837 (-0.001)	0.841 (+0.003)
Rhabdoid features	0.810	0.795 (-0.015)	0.798 (-0.013)
Bootstrap-corrected AUCs. Parentheses show changes from size alone, calculated before rounding; positive changes indicate improvement.

Changes compare each expanded model with size alone. Higher AUC and lower Brier score favor the expanded model. Differences lack CIs and external validation.

Summary

ITB was strongly correlated with tumor size; EP was less strongly correlated.
After adjustment for size, neither EP nor ITB was significantly associated with any of the five pathologic outcomes.
Adding EP or ITB to tumor size provided little improvement in prediction. Findings for sarcomatoid and rhabdoid features remain uncertain because few tumors had these features.

Supplemental analysis: Overall survival

Overall survival was estimated using the Kaplan–Meier method, separately by each pathologic finding. There were 405 patients with usable survival data, including 61 deaths; 6 records lacked usable follow-up or vital status. Each panel additionally excludes missing or nonapplicable pathology findings. Comparisons are unadjusted and exploratory.

Figure 2: Overall survival by pathologic findings. Shaded bands indicate 95% confidence intervals; marks indicate censoring. Tables show numbers at risk. Curves are displayed through five years.

Estimates for sarcomatoid and rhabdoid features should be interpreted cautiously because few tumors had these findings.