Analysis of factors affecting the upstaging and downstaging of renal cell carcinoma from T1 to T3a and the impact of different surgical approaches on patient prognosis and survival: a multicenter retrospective study

Introduction

Renal cell carcinoma (RCC) is among the most common malignant tumors of the urological tract, and its incidence has been increasing in recent years (1). Imaging evaluation plays a key role in early diagnosis and therapeutic decisions (2). Despite the continuous development of diagnostic imaging techniques, clinical staging of RCC is still challenging, especially given the inconsistency between preoperative imaging staging and postoperative pathological staging (3,4). This inconsistency manifests as upstaging and downstaging. “Upstaging” is the assignment of a lower tumor (T) stage based on imaging assessment and a higher T stage based on postoperative pathology; the opposite is true for “downstaging”. This phenomenon suggests that there may be errors in imaging assessment that affect surgical decision-making and treatment choice.

Most current studies focus on factors associated with upstaging, such as tumor size, morphological regularity, and location, and imaging scores such as the Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score (5); studies on the assignment of lower tumor stages have not been reported. Upstaging is usually accompanied by local invasion by the tumor or by the formation of more extensive lesions, both of which are associated with poorer prognosis (6,7). Downstaging reflects the scientific overassessment of imaging. The accuracy of staging influences the choice of surgical approach and is important for patients’ oncologic outcomes and quality of survival.

Patients with stage T1 disease usually have the option of partial nephrectomy (PN), which preserves renal function, whereas most patients with stage T3a disease require radical nephrectomy (RN) to ensure tumor control. The present study, unlike previous studies, focuses only on cT1 versus pT3a upstaging and cT3a versus pT1 downstaging. We analyzed these parameters in conjunction with the survival outcomes of the patients at our center. This is one of the few studies in which inconsistencies in staging, surgical modality selection and prognosis were explored in an integrated fashion. The objective of this study was to systematically assess the incidence of and the independent risk factors associated with staging discordance (both upstaging and downstaging) between T1 and T3a stages in patients with RCC and to evaluate the impact of upstaging and downstaging on the prognosis of patients in conjunction with survival analysis. The study was performed in hope of providing a more precise guide for clinical practice. To improve generalizability and reduce single-center bias, we expanded the study into a multicenter cohort including four tertiary hospitals in China. We present this article in accordance with the STROBE reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-2026-1-0043/rc).

Methods

Study design, setting, data source and participants

This was a retrospective multicenter cohort study including patients treated at four large-scale tertiary referral centers in China: (I) The First Affiliated Hospital of Xi’an Jiaotong University, (II) Baoji Central Hospital, (III) The Second Affiliated Hospital of Zhengzhou University, and (IV) The General Hospital of Ningxia Medical University. Consecutive adults (≥18 years) who underwent partial or RN between January 2013 and January 2023 were screened. Inclusion and exclusion criteria, imaging definitions, and outcome definitions were identical to those described previously. Data were extracted from the electronic medical record systems of each participating center and harmonized using a unified data dictionary, with predefined variable definitions and quality checks before pooling. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the institutional ethics committee of The First Affiliated Hospital of Xi'an Jiaotong University (No. 2023K-020) and individual consent for this retrospective analysis was waived. All participating hospitals were informed and agreed the study.

Covariates and measurement

The primary variables in this study included patient baseline characteristics, imaging features and pathological characteristics of their tumors, and surgery-related variables. Upstaging was defined as assignment of stage T1 after preoperative imaging with a change to stage pT3a based on postoperative pathology. Downstaging was defined as assignment of stage T3a after preoperative imaging with a change to stage pT1 based on postoperative pathology. The baseline characteristics of the patients included age, sex, body mass index (BMI), smoking history, alcohol consumption history, and the results of various biochemical tests.

Imaging characteristics included tumor diameter, morphology, size of margins, lesion location, tumor protrusion-to-intramural ratio, computed tomography (CT) difference, and PADUA score. Tumor morphology was classified as regular or irregular on the basis of preoperative imaging. Regular tumors are symmetrical, round or oval; irregular tumors are asymmetrical with lobulated, spiculated, or spiny projections. Tumor margins were classified as well-defined or ill-defined. Tumors with well-defined margins exhibit sharp, distinct borders between the tumor and the normal tissue. In tumors with ill-defined margins, the boundaries between the tumor and its surrounding structures are blurred and indistinct. Location is categorized on the basis of distance from the renal pelvis: central (tumor adjacent to the renal pelvis), intermediate (within 2 cm of the renal pelvis), and peripheral (more than 2 cm from the renal pelvis). The extent of tumor protrusion is categorized as confined to the renal parenchyma without protruding beyond the kidney surface, intermediate between protrusion and intrasubstantial, or fully protruding, where the tumor significantly protrudes beyond the kidney surface and may invade surrounding tissues. The CT difference is assessed via preoperative contrast-enhanced CT scanning and is defined as the enhancement value of the renal cortex minus the enhancement value of the normal renal cortex, reflecting the contrast between tumor tissue and normal renal tissue. The PADUA scoring system, which was developed by Ficarra et al. and has been widely adopted, is a standardized tool for assessing renal tumor complexity and surgical difficulty. PADUA scores range from 1 to 12, with 1–4 indicating low complexity, 5–8 indicating moderate complexity, and 9–12 indicating high complexity.

Data on the aforementioned parameters were obtained through preoperative contrast-enhanced CT and magnetic resonance imaging (MRI). To rigorously mitigate the inherent subjectivity of semantic features such as “irregular morphology” and “ill-defined margins”, a standardized evaluation protocol was implemented. All images were evaluated independently by two experienced urologists who were completely blinded to the patients’ clinical baseline characteristics and final pathological outcomes. In cases of discrepancy between the two primary evaluators, the images were re-reviewed jointly to reach a consensus. If a consensus could not be achieved, a third senior urogenital radiologists was consulted for final arbitration.

Pathological characteristics include cellular classification and International Society of Urological Pathology (ISUP) grading. The cellular classification includes clear cell carcinoma, papillary carcinoma, and clear cell carcinoma with atypia, as well as other types. ISUP grading follows the internationally recognized ISUP Pathological Grading System for RCC, which categorizes tumors as grade 1 to 4 on the basis of their nuclear morphological features, reflecting differentiation and aggressiveness. These characteristics of the tumors were determined through postoperative pathological examination and evaluated by pathologists who followed standardized procedures.

Surgical variables included surgical approach, affected-side glomerular filtration rate (GFR), unaffected-side GFR, and intraoperative blood loss. The surgical approach used in each case was determined on the basis of preoperative tumor staging. Intraoperative blood loss was obtained from surgical records, and GFR was assessed via preoperative tests of renal function. All clinical, radiological, and pathological data used in the study were systematically extracted from the electronic medical records system of the urology departments at the respective participating centers. The data were subjected to rigorous screening to ensure their accuracy and completeness, and missing information was obtained through telephone follow-up or medical record review.

Upstaging and downstaging were determined by comparing the clinical T stage (cT) based on preoperative imaging with the pathological T stage (pT) derived from postoperative histological examination. “Upstaged” refers to patients whose tumors were initially assessed as cT1 but whose postoperative pathology revealed tumor invasion extending to the pT3a stage. “Downstaged” refers to patients whose tumors were diagnosed as cT3a based on preoperative imaging but whose postoperative pathology confirmed tumor confinement within the kidney without invasion into extrarenal structures, thus requiring a downgrade to pT1. Evaluation was performed according to the tumor-node-metastasis (TNM) staging system provided by the American Joint Committee on Cancer (AJCC), 8th edition. As per these criteria, pathological stages are strictly determined by histological and anatomical extent: pT1 tumors are confirmed to be confined to the kidney and ≤7 cm in greatest dimension, whereas pT3a tumors exhibit locally aggressive morphological features, involving macroscopic extension into the major veins or microscopic/macroscopic invasion into the pelvicalyceal system, perinephric fat, or renal sinus fat, without breaching Gerota’s fascia. Correspondingly, clinical stages rely on radiological assessment: a tumor is classified as cT1 when preoperative imaging indicates a well-confined mass ≤7 cm without signs of extrarenal spread; conversely, a mass is classified as cT3a if contrast-enhanced imaging demonstrates one or more of the following distinct features of invasion: (I) perirenal fat invasion, defined as the presence of irregular or nodular soft-tissue densities extending beyond the renal parenchyma into the perirenal fat space, or significant stranding reaching Gerota’s fascia; (II) renal sinus fat invasion, characterized by direct extension into the renal sinus with obliteration, distortion, or frank infiltration of the normal low-density sinus fat interface; and (III) macroscopic venous invasion, indicated by visible intraluminal filling defects or abnormal focal expansion within the renal vein or its muscle-containing segmental branches.

Statistical analysis

Data analysis followed the prespecified plan. Continuous variables were expressed as mean ± standard deviation (SD) or median [interquartile range (IQR)] and compared using the Student’s t-test or Mann-Whitney U test, as appropriate; categorical variables were compared using the χ² or Fisher’s exact test. Determinants of upstaging and downstaging were evaluated using multivariable logistic regression, and survival was estimated by Kaplan-Meier analyses with log-rank tests. Two-sided P<0.05 was considered statistically significant.

Results

Descriptive statistics

Patients came from four participating centers, and baseline characteristics were generally comparable across centers according to preset data-quality checks. This study included 2,015 patients with RCC. Descriptive statistics for the clinical and pathological variables are presented in Table 1. The cohort was divided into four groups based on staging status: an upstaged group (cT1→pT3a, n=137), a T1 group (cT1→pT1, n=1,405), a downstaged group (cT3a→pT1, n=24), and a T3a group (cT3a→pT3a, n=449).

The mean tumor diameter in the upstaged group was 56.7±11.0 mm, significantly greater than the mean tumor diameters in the T1 group (52.6±7.6 mm) and the downstaged group (43.1±7.4 mm) (P<0.05). The PADUA score, a predictor of tumor complexity, indicated that 59.9% of the tumors in the upstaged group were highly complex, significantly greater than the 40.3% in the T1 group (P<0.05). Irregular tumor morphology was predominant in the upstaged group (65.7%) compared with 50.5% in the T1 group; the difference between the groups was statistically significant (P<0.05).

In terms of sex distribution, male patients predominated. The proportion of males was greater in the T1 group (64.6%) and the T3a group (67.5%) than in the upstaged group (60.6%) and the downstaged group (58.3%).

Tumor location distribution also varied across groups. The tumors in the upstaged group were predominantly located in the central renal region (44.5%), whereas the T3a group had a greater percentage of peripheral tumors (35.5%). The difference between the upstaged group (28.5%) and the downstaged group (16.7%) was statistically significant (P=0.02).

Other baseline characteristics, including BMI, smoking history, alcohol consumption history, and mean age at diagnosis of RCC, did not differ significantly among the groups (all P>0.05).

Survival analysis

We performed Kaplan-Meier survival analysis of overall survival (OS) and progression-free survival (PFS) across the four groups (upstaged, T1, downstaged, and T3a). The results revealed significant differences between the groups.

The median OS in the upstaged group was 76.1 months [95% confidence interval (CI): 66.5–85.7], significantly lower than the median OS in the T1 group (106.3 months, 95% CI: 103.2–109.4), the downstaged group (104.7 months, 95% CI: 90.5–118.9), and the T3a group (85.0 months, 95% CI: 78.9–91.2). The differences in OS between the upstaged group and the T1 group and between the downstaged group and the T3a group were statistically significant (P<0.05). However, the differences in OS between the T1 group and the downstaged group (P=0.82), between the T1 group and the T3a group (P=0.13), and between the downstaged group and the T3a group (P=0.57) were not statistically significant.

The median PFS in the upstaged group was 45.1 months (95% CI: 37.0–53.2); this was significantly lower than the PFS in the T1 group (97.4 months, 95% CI: 94.2–100.7), the downstaged group (100.4 months, 95% CI: 84.6–116.2), and the T3a group (80.6 months, 95% CI: 74.4–86.7). The differences in PFS between the upstaged group and the T1 group and between the downstaged group and the T3a group were statistically significant (P<0.05). However, the differences in PFS between the T1 group and the downstaged group (P=0.92), between the T1 group and the T3a group (P=0.16), and between the downstaged group and the T3a group (P=0.70) were not statistically significant.

The OS and PFS curves for the different groups are shown in Figures 1,2, respectively. Survival was significantly shorter in the upstaged group than it was in the other groups, but the differences in survival time between the T1 group and the downstaged group, the T1 group and the T3a group, and the downstaged group and the T3a group were not significant.

Figure 1 Kaplan-Meier analyses of OS. (A) Four-group comparison: T1 (cT1→pT1), upstaged (cT1→pT3a), T3a (cT3a→pT3a), downstaged (cT3a→pT1), P<0.001; (B) T1 vs. upstaged, P<0.001; (C) downstaged vs. T3a, P=0.047; (D) upstaged vs. T3a, P=0.04; (E) T1 vs. downstaged, P=0.71. cT, clinical tumor stage; OS, overall survival; pT, pathological tumor stage.

Figure 2 Kaplan-Meier analyses of PFS. (A) Four-group comparison: T1 (cT1→pT1), upstaged (cT1→pT3a), T3a (cT3a→pT3a), downstaged (cT3a→pT1), P<0.001; (B) T1 vs. upstaged, P<0.001; (C) downstaged vs. T3a, P=0.07; (D) upstaged vs. T3a, P<0.001; (E) T1 vs. downstaged, P=0.91. cT, clinical tumor stage; PFS, progression-free survival; pT, pathological tumor stage.

Univariate and multivariate analysis of upstaging

The results of the univariate analysis indicate that tumor diameter, tumor morphology, PADUA score, lesion location, and ISUP grade may influence the occurrence of upstaging (Table 2).

Multivariate logistic regression analysis further confirmed that tumor diameter [odds ratio (OR) =1.068; P<0.001], tumor morphology (OR =1.721; P=0.01), PADUA score (OR =1.634; P=0.003), and ISUP grade (OR =4.494; P<0.001) were independent risk factors for stage progression (Table 3). Specifically, each 1 cm increase in tumor diameter increased the risk of upward staging by approximately 1.93-fold, suggesting that larger tumors are more prone to external invasion. Compared with regular tumor morphology, irregular tumor morphology was associated with a greater risk of upward staging, indicating that irregular growth enhances tumor invasiveness. Patients with higher PADUA scores were more likely to experience upward staging, particularly those with more complex tumors, possibly because of increased susceptibility to invasion of adjacent tissues. Higher ISUP grading was associated with greater tumor invasiveness. In terms of lesion location, compared with central-type tumors, intermediate-type (OR =0.565; P=0.02) and peripheral-type (OR =0.547; P=0.01) tumors were associated with a lower risk of upward staging. This may be related to the proximity of central tumors to the renal sinus and hilum, which can lead to underestimation on imaging.

Univariate and multivariate analysis of downstaging

Univariate analysis indicated that tumor diameter, PADUA score, and lesion location may influence the occurrence of downstaging (Table 4).

Multivariate logistic regression analysis revealed that tumor diameter (OR =0.930; P=0.005) was a protective factor against downgrading, whereas the PADUA score (OR =2.476; P=0.02) was an independent risk factor (Table 5). Specifically, smaller tumor diameter was associated with a greater risk of downstaging, suggesting that smaller tumors are more prone to overestimation based on imaging. Tumors with higher PADUA scores were more likely to be overestimated, particularly those that exhibited endophytic growth or proximity to the renal sinus. In terms of lesion location, central tumors were more susceptible to downstaging than were intermediate (OR =0.184; P=0.004) and peripheral (OR =0.211; P=0.008) tumors. This suggests that central tumors, owing to their proximity to the renal collection system, are more likely than intermediate and peripheral tumors to be misinterpreted as invasive.

Discussion

This study focused on two types of staging inconsistencies that have important implications for surgical strategy and prognosis: upstaging of clinical T1 to pathological T3a and downstaging of pathological T3a to clinical T1. The core finding was that staging inconsistencies, although not highly prevalent, significantly alter therapeutic decision-making and impact outcomes when they do occur. Among the 2,015 patients in this cohort, 6.8% of the tumors examined were upstaged, and 1.2% were downstaged. A 2019 meta-analysis of 101,505 patients by Chen et al. (8) showed that upstaging of cT1 to pT3a occurred in approximately 5.5% of patients. The incidence of upstaging of T1 to pT3a was 5.7% in a systematic review of 21,869 cases included by Veccia et al. (9) in 2021. Multifactorial analysis suggested that tumor diameter, tumor morphology, PADUA score, and lesion location with ISUP grading were independent correlates of upstaging and that tumor diameter, PADUA score, and lesion location were independent correlates of downstaging. Survival comparisons revealed significant overall differences among the four groups; survival was ranked as worst in the upstaged group, second worst in the T3a group, and similar and best in the T1 and downstaged groups.

The challenge of staging discordance spans the entire T-stage spectrum. Providing a broader epidemiological perspective, Goodstein et al. (10) utilized the National Cancer Database (NCDB) to report remarkably high rates of pT3a upstaging in larger cT2a-b tumors (approaching 40%), alongside a 5.1% downstaging rate among cT3a masses. This aligns perfectly with our premise: conventional imaging frequently underestimates extrarenal micro-extension in localized masses, while paradoxically overestimating invasion in complex central tumors. However, as the authors acknowledged, national registries inherently lack granular morphological details and validated complexity metrics. Our multi-center study effectively bridges this evidence gap. While their NCDB analysis establishes the broad epidemiological prevalence of staging inaccuracies across larger tumors, our findings provide the underlying anatomical rationale for smaller (cT1) and complex masses. Specifically, we demonstrate that high PADUA scores and morphological irregularities independently drive these upstaging and downstaging phenomena. Together, these complementary findings underscore the necessity of incorporating multidimensional anatomical profiling to refine preoperative surgical planning.

Multifactorial logistic analysis of upstaging suggests that its occurrence is driven by a combination of specific, quantifiable clinical imaging features. Each 1 cm increase in tumor diameter was associated with an approximately 1.93-fold increase in the risk of upstaging, suggesting that larger tumor size reflects a higher propensity for extrarenal invasion (11-13). Some studies have also defined >4 cm as an independent threshold for upstaging, considering that the effect of size is clinically actionable and stratified (14). Tumor morphological irregularity is independently associated with upstaging of tumors; this is consistent with the characteristics of infiltrative growth reflected by morphological signs such as lobulation, spiculation, and unclear interface (15,16). According to the dynamic-enhanced CT radiomics study of Shimada et al. (17), tumor morphological irregularity (decreased sphericity) predicts pT3a upstaging in cT1b-T2N0M0 patients; moreover, higher PADUA scores are associated with a greater risk of upstaging of tumors, consistent with the combined characterization of unfavorable anatomical factors such as a high endogenous ratio and proximity to the collecting system or the renal sinus (18-20). The risk of upstaging is reduced in the intermediate and peripheral types compared with the central type, suggesting that the central zone is more likely to have real involvement as well as to be misdiagnosed on imaging because of its proximity to the renal sinus and hilum (21). Higher ISUP grade was also independently correlated with upstaging (22,23), reflecting a greater tendency of high-grade tumors to invade and break through. Overall, the combination of “size-morphology-location-complexity-grading” can define a phenotype that is more aggressive and tends to be underestimated in preoperative image interpretation. The rational explanation for this underestimation may be that detection of subtle invasion of the central or proximal renal sinus is limited by spatial resolution and by layer thickness on conventional enhanced CT, and the complexity of the interface between neighboring vessels, fat, and the collecting system and limited density contrast can be easily masked or confused with nonneoplastic changes (24), whereas postoperatively such involvement can be directly identified at the histological level. This is demonstrated by the presence of pT3a tumors, which, as noted in previous studies, may be difficult to identify in the presence of renal sinus fat, perinephric fat, and early venous invasion in conventional images. The ability to recognize early venous invasion is limited, and this is an important source of preoperative underestimation (25).

Within the framework of multifactorial analysis, downstaging of tumors is not an episodic phenomenon; rather, it depends on a set of quantifiable clinical and imaging features that together portray a pattern. The smaller the tumor diameter is, the greater is the likelihood of downstaging; this suggests that preoperative imaging is more inclined to elicit a biased overestimation of tumor invasion in smaller lesions than in large ones, whereas postoperative pathology for the most part confirms that smaller lesions are confined to the renal parenchyma. The higher the PADUA score is, the greater is the risk of downstaging, a finding that strongly reflects the phenomenon of imaging overestimation of sinus or perinephric invasion in complex central tumors. Tumors with elevated PADUA scores are intrinsically more complex, typically exhibiting endophytic growth patterns and intimate anatomical proximity to the renal sinus. Anatomically, the renal sinus is a highly confined space containing a dense network of veins, collecting system structures, and adipose tissue. In such anatomically crowded central regions, conventional contrast-enhanced CT is frequently challenged by partial volume averaging and limited spatial resolution. Consequently, an expansile but benign ‘pushing margin’, localized peritumoral inflammatory edema, or fibrotic pulling from a central mass can easily be mischaracterized as frank sinus fat or venous invasion. These imaging artifacts and non-neoplastic peri-tumoral changes frequently drive a defensive preoperative overcall (cT3a) by radiologists and surgeons aiming to ensure maximum oncologic safety. However, when definitive histopathology confirms that the tumor pseudocapsule remains intact and the mass is strictly confined to the renal parenchyma, the clinical scenario ultimately manifests as a pT1 downgrade. Recognizing this diagnostic pitfall is paramount for maximizing nephron-sparing opportunities, ensuring that patients with complex, yet intrinsically organ-confined masses are not erroneously deprived of PN.

Survival outcome follows the same clinical logic as do the above hazard profiles: the upstaged group exhibits the worst survival, the T3a group exhibits the second worst, and survival in the T1 group is similar to and better than that in the downstaged group (Figure 1A) (19,26). A study of an institutional cohort by Lai et al. (22) similarly revealed that the 5-year OS and PFS of individuals whose tumors were upstaged from cT1 to pT3a were significantly lower than those of individuals whose tumors were downstaged to pT1. NCDB-based nationwide analyses have also demonstrated that an increased risk of death among clinical T1 patients is associated with an increased overall risk of death when pathological upstaging occurs (27). This outcome is more likely due to a combination of “increased biological aggressiveness” and untimely or inadequate treatment arising from preoperative underestimation. The former results from the propensity of the disease to break through because of greater tumor load and higher grade differentiation, whereas the latter is related to the difficulty in identifying central lesions on conventional imaging. This problem may influence the choice of surgical procedure, margin strategy, and intensity of follow-up. The poorer OS exhibited by the upstaged group in comparison with the T1 group is due mainly to the presence of extrarenal involvement that was not recognized preoperatively in the upstaged population, the choice of PN based on preoperative underestimation in patients who should have undergone RN, and to more conservative margin management, which increases the risk of long-term mortality. Thus, clinical alertness should be increased in advance in suspected cT1 patients, with improved imaging and intraoperative calibration (12) (Figure 1B). The finding that upstaged patients are still inferior to T3a patients in terms of OS, even when their final pathology is pT3a, indicates that inadequate treatment initiation and intensity due to underestimation at the time of preoperative staging can directly affect the outcome. For example, patients who should have undergone RN were selected for PN, with relatively conservative resection extent and margin control, and subsequent follow-up and reassessment were weak, resulting in lower long-term survival than patients whose tumors were staged as T3a in the beginning and who underwent radical first-line nephrectomy. Beyond these surgical factors, we hypothesize that this survival discrepancy is multifactorial, driven by intrinsic tumor biology, the compounded risk of tumor size, and statistical limitations. Biologically, a relatively small tumor (cT1, ≤7 cm) that has already demonstrated the capacity for local extrarenal invasion (pT3a) likely harbors a more aggressive phenotype than a cT3 tumor that achieves local invasion primarily through prolonged, expansive growth. Furthermore, within the cT1 spectrum, larger tumor diameter inherently confers a higher baseline risk. As observed in our cohort, the mean tumor diameter in the upstaged group (56.7±11.0 mm) was significantly larger than that in the stage-concordant T1 group (52.6±7.6 mm) and the downstaged group (43.1±7.4 mm) (P<0.05). From a statistical perspective, we must acknowledge that the objective clinical rarity of cT1-to-pT3a upstaging inherently limits the available cohort size. This relatively small sample size may render the upstaged subgroup more susceptible to statistical outliers, potentially amplifying the magnitude of the observed survival difference despite our multi-center design. Therefore, in clinical practice, such risks need to be mitigated via thin-slice multiphase imaging, joint radiological review, and intraoperative frozen section (IFS) analysis (Figure 1D). The difference in OS between the T1 group and the T3a group reflects not only baseline differences in biology due to the presence or absence of extrarenal involvement but also differences in staging-driven surgical procedures. For T1 tumors, PN was used, whereas for T3a tumors RN was preferred for control of extravasation. The difference in the outcomes observed in the two cases can be interpreted as a result of the combination of pathological status and matched operative modality; this suggests that the selection of surgical modality according to stage was overall appropriate. In pairwise comparisons of PFS, upstaged patients were more likely to recur or progress in the early to midterm period than were T1 patients; thus, their follow-up needs to be more intensive and anterior (12) (Figure 2B). The survival of those in the upstaged group is similarly unfavorable compared with those in the T3a group, suggesting that differences in the starting pathway not only affect long-term survival but also have an impact on midterm progression and that perioperative pathology and border assessment should be routinely introduced during the perioperative period (28) (Figure 2D). The superiority of T1 over T3a still holds for PFS, suggesting that true extrarenal involvement is a major determinant of the risk of recurrence (29) and that in cases of suspected involvement, intraoperative interface verification and margin management should be intensified to minimize subsequent passive intensification.

The “size-morphology-location-complexity-gradation” risk profile revealed in this study provides a clearer basis for choosing between PN and RN. For clinical T1 lesions that are large, have irregular contours, have high PADUA scores, and are located in the central region, the dual-track plan of ‘renal preservation and radical treatment’ might be considered preoperatively. Intraoperative rapid-freezing pathology and critical interface assessment could potentially serve as references for surgical decision-making. When possible renal sinus or perirenal involvement, suspicious margins, or limited exposure are observed, conversion to the radical pathway might be considered as an option to ensure oncologic safety, though the clinical efficacy of this approach warrants future prospective investigation (30). Yoshida et al. (26) reported that the 5-year recurrence-free survival (RFS) after PN was significantly lower than that after RN in patients with cT1 who had been upgraded to pT3a, with renal vein invasion being a significant predictor of recurrence in the PN population, suggesting that more stringent border and venous access treatments are needed when venous or renal sinus involvement is suspected preoperatively and a need for border and venous access management, with follow-up moving forward with intensification. In contrast, in cases of clinical T3a in which the tumor is small and there is an ambiguous interface of central regional signs, the possibility of imaging overestimation needs to be fully considered, and the feasibility of preserving the renal unit should be preferentially evaluated under strict margin management and intraoperative calibration to avoid performing a one-size-fits-all radical surgery because of false positives (31). On the basis of a propensity score matching analysis of data in the Surveillance, Epidemiology, and End Results (SEER) database, Tian et al. (32) reported that RN and PN in patients with limited pT3a had comparable oncologic outcomes, suggesting that PN is a feasible option for partial T3a cases in which strict screening is conducted and margins are negative. At the follow-up level, a systematic review recommended closer follow-up for patients with upstaging (8), with priority given to local recurrence and venous-related events, whereas for patients with renal unit preservation due to suspected imaging overestimation, imaging and functional assessment should be strengthened during initial follow-up to ensure oncologic safety. Further translational directions include the construction of preoperative risk scores or line graphs centered on “size-morphology-location-complexity” and use of these scores to translate the intervening factors behind survival differences into actionable clinical pathways (33,34). Accurate preoperative evaluation and risk stratification of renal masses are crucial not only for ensuring oncological control but also for preserving postoperative renal function. As highlighted in a multicenter study by Pecoraro et al. (35), even patients with two kidneys and preserved baseline renal function face a non-negligible risk of acute kidney injury and new-onset clinically significant chronic kidney disease following surgery, particularly those with highly complex tumors. Importantly, the procedure itself is not the only determinant (36), and clean margins and adequate management of the suspected invasive interface are the core of oncologic safety (37); with this caveat, PN has the potential to provide long-term renal and cardiorenal benefits in young patients and in those with limited renal reserve, whereas RN might be a reasonable consideration in cases in which extrarenal involvement is confirmed or highly suspected. The above strategy allows the chain of “preoperative stratification-intraoperative calibration-postoperative follow-up” to be used to better match the surgical approach to the true pathology and to reduce undertreatment due to underestimation and overtreatment due to overestimation.

Despite these robust clinical implications, several limitations of the present study must be acknowledged. First, although the multicenter design is a key strength that improves external validity and reduces single-institution bias compared with prior single-center series, residual between-center heterogeneity may remain. Due to strict data anonymization protocols implemented during the multi-institutional data aggregation, specific hospital identifiers were removed at the source. Consequently, we were unable to utilize mixed-effects models to statistically adjust for this potential heterogeneity. However, we believe this limitation is largely mitigated by the fact that all four participating institutions are leading tertiary hospitals in the same region, sharing highly comparable imaging protocols, surgical expertise, and standardized therapeutic strategies. Second, and perhaps more importantly, our study relied on conventional semantic imaging features, such as ‘irregular morphology’ and ‘ill-defined margins’. Although we implemented a rigorous, double-blinded evaluation protocol involving multiple experienced imaging specialists to minimize subjective bias, visual assessments inherently carry an unavoidable degree of inter-observer variability. As a crucial future direction to overcome this bottleneck, the integration of automated radiomics and artificial intelligence (AI)-based contouring holds immense potential. By extracting high-dimensional, sub-visual quantitative imaging biomarkers, AI-driven models can effectively eliminate human subjectivity, standardize morphological definitions, and ensure high reproducibility. Finally, owing to the naturally low clinical incidence of genuine downstaging (1.2% in our cohort), the sample size of the downstaged group (n=24) was relatively small. This inherently limits the statistical power of the multivariable regression analysis for this subgroup; thus, the identified predictors for downstaging should be interpreted with caution as exploratory findings and validated in future large-scale cohorts.

Conclusions

In conclusion, this multicenter study delineates the independent risk factors for the occurrence of upstaging and downstaging of renal tumor stage by systematically evaluating the discordance between preoperative imaging staging and postoperative pathological staging in patients with RCC and assesses the impact of upstaging and downstaging on patients’ prognoses in combination with survival analysis. We found that the risk profiles associated with upstaged and downstaged tumors are not only closely related to the anatomical features and biological behaviors of the tumor but also reflect limitations in radiological assessment in some cases. This study provides a systematic framework for preoperative assessment in the clinic, aiming to rationally triage patients with upstaged and downstaged tumors by improving the accuracy of imaging identification and to then optimize the treatment strategy and improve the patient’s prognosis. Future studies should focus on validation using larger multicenter cohorts, the deep integration of AI-driven imaging technologies, and multidisciplinary collaboration to further improve the accuracy of preoperative assessment and provide a more solid foundation for the development of individualized treatment plans.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-2026-1-0043/rc

Data Sharing Statement: Available at https://tau.amegroups.com/article/view/10.21037/tau-2026-1-0043/dss

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Funding: This work was supported by the National Natural Science Foundation of China (grant No. 82373181).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2026-1-0043/coif). J.Z. reports that this work was supported by the National Natural Science Foundation of China (grant No. 82373181). The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Approval to conduct the study was granted by the Ethics Committee of The First Affiliated Hospital of Xi’an Jiaotong University (No. 2023K-020), and according to Chinese legislation, retrieval of informed consent was not required for this retrospective study. All participating hospitals were informed and agreed to the study.

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