A comparative analysis of clinicopathological characteristics and surgical outcomes in adults with renal masses

Abstract

Background:

The management of renal masses varies significantly across age groups, necessitating a comprehensive understanding of age-related clinicopathological characteristics. This study evaluates these characteristics and surgical outcomes in patients aged ≤45 years versus >45 years.

Aim:

The aim of the study was to evaluate the relationship between preoperative neutrophil-to-lymphocyte ratio (NLR), patient age, tumor-node-metastasis (TNM) stage, and long-term survival in renal cell carcinoma (RCC), and to assess whether NLR can improve risk stratification beyond conventional clinicopathologic factors.

Materials and Methods:

A retrospective analysis of 199 patients with renal space-occupying lesions was conducted between January 2018 and December 2024. Patients were stratified by age (≤45 years: n = 64; >45 years: n = 135). Demographics, clinical presentations, histopathology, surgical approaches, and perioperative parameters were analyzed using appropriate statistical methods.

Results:

Older patients more frequently experienced flank pain (76.4% vs. 58.1%) and hematuria (50.3% vs. 34.4%), and had higher nodal (N1: 9 vs. 1) and metastatic (M1: 28 vs. 2) disease rates compared to those ≤45 years. Clear-cell RCC remained most common (43.2% across groups). Postoperative creatinine rose significantly in all nephrectomy types, whereas hemoglobin changes were similar by age. Preoperative NLR increased with pT stage (P < 0.001), was higher in node-positive (P = 0.030) and metastatic (P < 0.001) cases, underscoring its independent prognostic value across age strata.

Conclusions:

Age significantly influences the clinical presentation and disease stage of renal masses. Histologic subtypes were similar across ages, but older patients consistently had more advanced disease. Moreover, elevated preoperative NLR was strongly linked to higher TNM stage, underscoring its value in RCC risk stratification.

INTRODUCTION

Renal masses encompass a spectrum from benign angiomyolipomas and oncocytomas to malignant renal cell carcinoma (RCC). Although RCC most commonly emerges in patients in their 60s and 70s, a meaningful subset presents before age 45, where inherited syndromes, unique molecular drivers, and potentially indolent clinical courses remain poorly characterized.[1,2,3,4] By contrast, older adults–with competing comorbidities and less aggressive screening–often face delayed diagnoses and more advanced disease. Existing studies conflict on whether younger age confers more favorable pathology, smaller tumors, or distinct histologic subtypes, and few address how age shapes postoperative renal function or the incidence of sarcomatoid and rhabdoid differentiation.[1,2,3,4] To fill these gaps, we systematically compared patients ≤45 versus >45 years across histopathology, symptom profiles, tumor-node-metastasis (TNM) stage, tumor size, aggressive differentiation, and perioperative renal and hematologic outcomes, aiming to define age-tailored management strategies for renal masses.

MATERIALS AND METHODS

Study design and population

A retrospective review was conducted of all patients who were diagnosed as having renal space-occupying lesions and undergoing partial, radical, or cytoreductive nephrectomies or biopsy for the same, between January 2018 and December 2024 at a single tertiary care center.

Inclusion criteria were

1. Age ≥18 years

2. Confirmed renal mass (benign or malignant) by imaging and pathology

3. Definitive surgical management with available clinical and pathological data.

Exclusion criteria

1. Patients with incomplete investigations

2. Patients who declined participation

3. Patients who were lost to follow-up.

Data collection

Clinical variables extracted from electronic medical records included age at diagnosis, sex, presenting symptoms (flank pain, hematuria, abdominal mass, fever, and incidental discovery), relevant laboratory parameters (serum creatinine, blood urea, and hemoglobin), and tumor size. Each patient’s surgical procedure (partial, radical, or cytoreductive nephrectomy) and postoperative course were also recorded.

Histopathological evaluation

Histopathological specimens were examined by dedicated genitourinary pathologists. Tumor subtypes were characterized (clear cell RCC, papillary RCC, chromophobe RCC, oncocytoma, angiomyolipoma, etc.), and the presence of sarcomatoid or rhabdoid differentiation was specifically noted.

Staging

All patients had contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) for clinical staging. Tumors were staged according to the TNM system. Postoperative staging was based on final pathology reports.

Statistical analysis

Patients were categorized into two groups: ≤45 years (n = 64) versus >45 years (n = 135). Chi-square tests were used to assess categorical variables (e.g., histopathology subtype, T/N/M staging), while independent t-tests were applied for continuous measures (e.g., tumor size). Pre- and postoperative creatinine and hemoglobin levels were compared using paired t-tests. A P < 0.05 was considered significant. SPSS Statistics (Version 25, IBM Corporation, Armonk, NY, USA) was employed for data analysis. Median follow-up was determined via the reverse Kaplan–Meier method. Event rates for overall-survival (OS) and DFS are reported at 1-, 3-, and 5-year landmarks. Censoring was applied at the loss to follow-up or the study cutoff date of December 31, 2024.

Ethical considerations

The study adhered to the Declaration of Helsinki guidelines. Institutional ethical clearance was taken for the study with IEC letter no. AIIMS/IEC/25/26. The study adhered to STROBE guidelines.

RESULTS

A total of 199 patients (135 aged >45 and 64 aged ≤45) [Table 1] were included in the study. The key findings regarding age distribution among study participants were as follows:

Table 1.

Histopathology type distribution by age group

Histopathology type	≤45 years (n=64), n (%)	>45 years (n=135), n (%)	P
Clear cell RCC	28 (43.75)	58 (42.96)	0.82
Papillary RCC	12 (18.75)	25 (18.52)	0.91
Chromophobe RCC	8 (12.50)	18 (13.33)	0.88
Others
Benign pathology
Tuberculosis, Hydatid cyst, Aspergillosis	6 (9.38)	9 (6.67)	0.568
Benign tumors
Angiomyolipoma	1 (1.56)	7 (5.19)	0.441
Oncocytoma	4 (6.25)	6 (4.44)	0.730
Malignant tumors
TCC/UTUC	3 (4.69)	11 (8.15)	0.555
Leiomyosarcoma	1 (1.56)	0	0.322
Dedifferentiated liposarcoma	1 (1.56)	0	0.322
Adenocarcinoma metastatic deposits	0	1 (0.74)	1.000
Total	16 (25.00)	34 (25.19)	0.94

RCC: Renal cell carcinoma, TCC: Transitional cell carcinoma, UTUC: Upper tract urothelial carcinoma

• Overall median age: 53.0 years

• Median age by groups:

  • Patients >45 years: 60.0 years

  • Patients ≤45 years: 38.5 years.

• Age range: 18–88 years.

Histopathological types and their incidence in patients aged ≤45 versus >45 years

• Clear cell RCC was the most prevalent (43.22%) histopathological subtype in both age groups (86/199) [Table 1]

• No significant age-related differences were observed in the distribution of tumor subtypes [Table 1]

• Considering the above results, one more analysis was done after lowering the age cutoff to 25 years.

The analysis revealed several notable differences in the histology distribution between patients aged ≤25 years and those >25 years. Clear Cell Carcinoma exhibited the largest discrepancy, being 54.5% prevalent among younger patients compared to 75.0% in the older group–a difference of −20.5%. In addition, other histological types were more frequently observed in the younger cohort, with other histology showing a +7.5% difference, papillary carcinoma a +7.0% difference, chromophobe carcinoma a +5.4% difference, and urothelial carcinoma a +4.8% difference. Conversely, certain histology, including oncocytoma (2.1%), angiomyolipoma (1.1%), and sarcoma (1.1%), were identified exclusively in patients over 25 years of age. Despite these variations, none of the differences reached statistical significance (P < 0.05), likely due to the small sample size of the younger age group (n = 11) compared to the older group (n = 188).

Clinical presentations (flank pain, hematuria, fever, abdominal mass, or incidental) and their correlation with age groups

• Flank pain and hematuria were significantly more frequent in patients aged >45 (P < 0.05) [Table 2]

• Patients aged >45 years had more symptomatic patients (P < 0.05) [Table 2].

Table 2.

Clinical presentation by age group

Presentation	≤45 years (n=64), n (%)	>45 years (n=135), n (%)	P
Flank pain	44 (65.63)	108 (76.38)	0.04
Hematuria	25 (39.06)	75 (50.25)	0.03
Incidental	17 (23.44)	26 (16.30)	0.12
symptomatic	47 (73.43)	109 (80.74)	0.045

Preoperative tumor-node-metastasis staging and its correlation with the age of the patient

• N1 disease and M1 disease were significantly higher in patients aged >45 years (P < 0.05) [Table 3].

Table 3.

Preoperative tumor-node-metastasis staging by age group

	Age >45	Age ≤45	Total	P
Clinical T staging
T1A	18	12	30	0.184
T1B	11	6	17
T2A	2	1	3
T2B	1	2	3
T3A	73	34	107
T3B	0	1	1
T3C	1	0	1
T4	29	8	37
Subtotal	135	64	199
Clinical N staging
N0	126	63	189	0.045
N1	9	1	10
Subtotal	135	64	199
Clinical M staging
M0	107	62	169	0.001
M1	28	2	30
Total	135	64	199

Postoperative histopathological tumor-node-metastasis staging and its correlation with patient age

• Older patients had more nodal disease (N1) compared to younger counterparts, reflecting higher pathologic stage [Table 4]

• Since routine lymph node dissection was not done in all patients hence 170 patients are classified as Nx staging in our study

• Among the 29 patients in which clinically enlarged lymph nodes were present and removed during surgery, 4 were positive for malignancy.

Table 4.

Pathological tumor-node-metastasis staging by age group

	Age >45	Age ≤45	Total	P
Pathological T
T1A	34	15	49	0.419
T1B	27	14	41
T2A	10	7	17
T2B	8	7	15
T3A	24	10	34
T4	6	6	12
Subtotal	109	59	168
Pathological N
N0	13	12	25	0.042
N1	3	1	4
NX	119	51	170
Total	135	64	199

Size of tumors and their association with the patient’s age

Mean tumor size did not differ significantly between groups, indicating that tumor dimension alone may not predict age-based staging differences [Table 5].

Table 5.

Tumor size comparison by age group

Group	n	Mean (cm)±SD	F	Significant
≤45	64	7.086±4.0299	2.431	0.121
>45	131	7.103±2.9576

Rhabdoid and sarcomatoid differentiation by age

Rhabdoid and sarcomatoid differentiation remained uncommon in both age groups and showed no statistically significant variation [Table 6].

Table 6.

Differentiation (sarcomatoid/rhabdoid) by age group

Percentage of differentiation	Age >45	Age ≤45	Total	P
Sarcomatoid
0.00	131	62	193	0.821
10.00	1	0	1
15.00	1	1	2
30.00	1	0	1
90.00	1	1	2
Subtotal	135	64	199
Rhabdoid
0.00	126	64	190	0.215
1.00	1	0	1
15.00	1	0	1
100.00	7	0	7
Total	135	64	199

Outcomes of partial versus radical versus cytoreductive nephrectomy in terms of pre- and postoperative creatinine and hemoglobin changes

Postoperative hemoglobin was done on postoperative day 1, and the change in value compared to preoperative was evaluated [Table 7].

Table 7.

Change in creatinine value was observed at 4 weeks postoperatively and compared with preoperative creatinine

	Change in creatinine values	Change in Hemoglobin values
Biopsy	Not applicable	Not applicable
Partial nephrectomy	0.09	0.46
Radical nephrectomy	0.36	0.60
Cytoreductive nephrectomy	0.38	1.02

Patients >45 years (135 patients):

• Biopsy: 21 cases

• Partial nephrectomy: 21 cases

• Radical nephrectomy: 87 cases

• Cytoreductive nephrectomy: 6 cases.

Patients ≤45 years (64 patients):

• Biopsy: 1 case

• Partial nephrectomy: 15 cases

• Radical nephrectomy: 47 cases

• Cytoreductive nephrectomy: 1 case.

Total procedures across all patients:

• Biopsy: 22 cases

• Partial nephrectomy: 36 cases

• Radical nephrectomy: 134 cases

• Cytoreductive nephrectomy: 7 cases

• Creatinine levels increased significantly postoperatively in cytoreductive nephrectomy, followed by radical nephrectomy, and least in partial nephrectomy (P < 0.001) [Table 7 and Figure 1]

• Hemoglobin changes were not statistically significant (P = 0.979).

Figure 1.

Change in creatinine and hemoglobin

Preoperative neutrophil-to-lymphocyte ratio and its relation with pathological tumor-node-metastasis staging

We conducted an analysis to examine the association between preoperative neutrophil-to-lymphocyte ratio (NLR) and TNM staging in our cohort of kidney cancer patients. NLR is an established marker of systemic inflammation that has been associated with cancer progression and outcomes in various malignancies.

Our analysis revealed significant associations between preoperative NLR and tumor staging parameters:

• Patients with nodal involvement (N1+) had significantly higher preoperative NLR (mean: 6.58) compared to those without nodal involvement (N0, mean: 3.22; P = 0.0302) [Figures 2 and 3]

• Patients with metastatic disease (M1) had significantly higher preoperative NLR (mean: 6.57) compared to those without metastasis (M0, mean: 3.26; P < 0.0001) [Figures 3 and 4]

• Higher preoperative NLR was associated with more advanced T stages, particularly in pathological staging [Figures 5-9]

  Figure 6.

  

  Box plot showing pre-operative neutrophil-to-lymphocyte ratio by pathological T staging

  Figure 7.

  

  Scatter plot with regression line showing the relationship between clinical T stage and pre-operative neutrophil-to-lymphocyte ratio

  Figure 8.

  

  Scatter plot with regression line showing the relationship between pathological T stage and pre-operative neutrophil-to-lymphocyte ratio

• These findings suggest that preoperative NLR may serve as a valuable biomarker for assessing tumor burden and progression in kidney cancer patients.

Figure 2.

Box plot showing pre-operative neutrophil-to-lymphocyte ratio by pathological N staging

Figure 3.

Bar chart of mean pre-operative neutrophil-to-lymphocyte ratio by staging categories

Figure 4.

Box plot showing pre-operative neutrophil-to-lymphocyte ratio by clinical M staging

Figure 5.

Box plot showing pre-operative neutrophil-to-lymphocyte ratio by clinical T staging

Figure 9.

Bar chart of mean pre-operative neutrophil-to-lymphocyte ratio by T staging categories

The consistent association of NLR with T, N, and M staging parameters strengthens its potential clinical utility as a prognostic indicator for kidney cancer patients. This simple and readily available biomarker could potentially aid in risk stratification and treatment planning.

Survival analysis and follow-up

At baseline (time 0), survival probability is 100%. During the 1^st year, a modest decline is observed as early events accrue, with the probability of survival at 12 months estimated at 94.7% (vertical dashed line at 12 months). After the 1^st year, the curve plateaus, indicating minimal additional mortality; at 24 months, the survival probability remains high at 93.2% (vertical dashed line at 24 months). The x-axis denotes follow-up time in months, and the y-axis shows estimated survival probability. A light grid enhances interpretability, and the solid blue line is labeled “OS.” These Kaplan–Meier estimates demonstrate that most deaths occur within the 1^st year postsurgery, with long-term survival stabilizing thereafter [Figure 10].

Figure 10.

Illustrates the adjusted overall‐survival curve for the entire cohort over a 24-month follow-up period

Preoperative neutrophil-to-lymphocyte ratio and survival outcomes

In addition to examining the relationship between NLR and TNM staging, we conducted further analysis to investigate the association between preoperative NLR and survival outcomes in our cohort of kidney cancer patients.

The analysis included a total of 199 patients. The mean NLR in the overall cohort was 3.76 ± 2.54. Patients who survived had a mean NLR of 3.27 ± 2.53, while nonsurvivors had a significantly higher mean NLR of 4.61 ± 2.32 (P = 0.0002).

To further explore the relationship between NLR and survival, we categorized NLR values into three groups based on quartiles: low (≤1.85), medium (1.85–5.64), and high (>5.64) [Figures 11-13]. The survival rates were:

Figure 11.

Distribution of pre-operative neutrophil-to-lymphocyte ratio by survival status

Figure 13.

Receiver operating characteristic curve for neutrophil-to-lymphocyte ratio as a predictor of survival

• Low NLR: 82.0% survival rate

• Medium NLR: 64.6% survival rate

• High NLR: 44.0% survival rate.

Figure 12.

Survival rates by neutrophil-to-lymphocyte ratio category

Receiver operating characteristic curve analysis was performed to evaluate the predictive value of NLR for survival. The area under the curve was 0.68, indicating moderate predictive ability. The optimal cutoff value for NLR to predict survival was determined to be 3.95 [Table 8].

Table 8.

Summary of neutrophil-to-lymphocyte ratio and survival analysis

Parameter	Value
Number of patients	199
Mean NLR (overall)	3.76±2.54
Mean NLR in survived patients	3.27±2.53
Mean NLR in nonsurvived patients	4.61±2.32
P-value (NLR difference by survival)	0.0002
Optimal NLR cutoff for survival prediction	3.95
AUC for NLR as survival predictor	0.68

NLR: Neutrophil-to-lymphocyte ratio, AUC: Area under the curve

These findings suggest that preoperative NLR is not only associated with TNM staging parameters but also serves as an independent predictor of survival in kidney cancer patients. Higher NLR values correlate with poorer survival outcomes, highlighting the potential utility of this readily available biomarker in risk stratification and treatment planning.

DISCUSSION

Renal masses, also known as kidney tumors, are abnormal growths that can occur in the kidney. These masses can be benign or malignant, with RCC being the most common type of kidney cancer.[1] Understanding the epidemiology, symptomatology, diagnostic approaches, treatment modalities, and outcomes of renal masses is crucial for effective management and improved patient outcomes.

Renal masses are relatively rare, accounting for approximately 3% of all adult cancers.[2] The incidence of RCC has been increasing over the past few decades, with a reported annual increase of 2%–3%.[3] RCC is more common in men than women, with a male-to-female ratio of 1.5:1.[4] The majority of RCC cases occur in individuals aged 50–70 years, although it can also occur in younger adults.[5]

Renal masses can present with a range of symptoms such as hematuria (blood in the urine), flank pain, abdominal mass, weight loss, and fatigue. However, many renal masses are asymptomatic and are incidentally detected during imaging studies for unrelated reasons.[6]

This retrospective analysis reveals that patients >45 years are more likely to present with symptomatic renal masses–chiefly flank pain and hematuria–and harbor advanced disease (N1, M1) preoperatively. These findings align with prior reports suggesting older age correlates with delayed detection or intrinsically more aggressive disease. By contrast, younger individuals (≤45) often discover renal tumors incidentally, possibly due to imaging done for unrelated reasons.[5,6]

The diagnostic workup for renal masses typically involves CT scans, MRI, ultrasound, Complete blood count, blood chemistry tests, and urinalysis.

The treatment of renal masses depends on the size, location, and histology of the tumor, as well as the patient’s overall health. Surgical treatment options include Partial nephrectomy, radical nephrectomy, or cytoreductive nephrectomy.

The outcomes of renal masses vary depending on the stage and histology of the tumor. The 5-year survival rate for patients with localized RCC is approximately 90%, while those with metastatic disease have a 5-year survival rate of around 10%.[7]

Factors that influence outcomes include tumor size, grade, and stage, as well as the presence of sarcomatoid or rhabdoid differentiation. In our study, tumor size did not differ by age, indicating that size alone cannot explain the higher metastatic burden in older patients. Our data also demonstrate that the prevalence of sarcomatoid and rhabdoid differentiation, although rare, does not vary by age group. This underscores that these aggressive features may arise independently of patient age.[7,8]

Importantly, creatinine levels rose significantly after surgery in all nephrectomy types (partial, radical, or cytoreductive). This highlights the need for nephron-sparing strategies, especially in younger patients who face potential long-term renal insufficiency. Hemoglobin levels were largely maintained, suggesting that modern surgical techniques allow for acceptable perioperative blood management.[9]

This study also demonstrates significant associations between elevated preoperative NLR and advanced TNM staging parameters in kidney cancer patients. Our findings suggest that NLR, a readily available and cost-effective biomarker, may provide valuable prognostic information complementary to conventional staging systems.

The observed association between elevated NLR and advanced pT staging aligns with previous studies in various malignancies.[10,11] This relationship may reflect the increasing systemic inflammatory response associated with more extensive primary tumor invasion. As tumors grow and invade surrounding tissues, they induce local inflammation and release inflammatory mediators that can trigger a systemic inflammatory response, characterized by neutrophilia and relative lymphopenia.[12] In addition, larger tumors may experience central necrosis, further amplifying the inflammatory response.[13]

The significant association between elevated NLR and regional lymph node involvement (pN1+) observed in our study is consistent with findings from previous investigations in other solid tumors.[14] This relationship may be explained by the role of inflammation in promoting lymphatic invasion and lymph node metastasis. Inflammatory mediators can enhance tumor cell motility, invasiveness, and lymphangiogenesis, facilitating lymphatic spread.[15] Furthermore, neutrophils may directly promote lymphatic invasion through the release of matrix metalloproteinases and other proteolytic enzymes that degrade the extracellular matrix.[16]

Perhaps most notably, our study demonstrated a strong association between elevated NLR and the presence of distant metastasis (cM1). This finding is particularly relevant from a clinical perspective, as metastatic disease represents the most significant determinant of prognosis in kidney cancer patients.[17] The substantial difference in NLR between patients with and without metastasis suggests that NLR may serve as a surrogate marker of metastatic potential. The biological mechanisms underlying this association may involve neutrophil-mediated promotion of the metastatic cascade, including facilitation of tumor cell intravasation, survival in circulation, and extravasation at distant sites.[18]

From a practical standpoint, the associations observed in our study suggest that preoperative NLR may serve as a valuable adjunct to conventional staging systems in kidney cancer. As a simple, inexpensive, and widely available biomarker, NLR could potentially enhance risk stratification and guide treatment decisions, particularly in resource-limited settings where advanced molecular biomarkers may not be accessible.[19] For instance, patients with early-stage disease but elevated NLR might benefit from more intensive surveillance or consideration of adjuvant therapy, given their potentially higher risk of disease progression.[20]

Limitations

Our study includes a single-institution, retrospective design. Future multicenter trials and molecular studies would further clarify hereditary influences, younger-age tumor biology, and optimal nephron-sparing approaches. A single preoperative value of NLR was taken for consideration of evaluation in the study; sequential values or postoperative values were not thoroughly evaluated in terms of their relevance.

Future directions

Prospective, multi-institutional analyses focusing on molecular markers are warranted to better characterize age-specific differences in RCC. Moreover, evaluating the impact of nephron-sparing strategies and targeted therapies on renal function preservation across different age brackets remains an important area of ongoing research.

CONCLUSIONS

In this cohort, patients aged >45 years presented more frequently with flank pain and hematuria, higher nodal involvement (N1), and a higher rate of metastatic (M1) disease. Conversely, tumor size, histopathological subtypes, and sarcomatoid/rhabdoid differentiation were similar across age groups. Understanding these age-specific nuances is vital for optimizing clinical management, emphasizing early detection in older patients, and preserving renal function in younger individuals through nephron-sparing techniques wherever feasible.

This study also demonstrates significant associations between elevated preoperative NLR and advanced TNM staging parameters in kidney cancer patients. Higher NLR values were consistently observed in patients with more extensive primary tumor invasion (advanced pT stage), regional lymph node involvement (pN1+), and distant metastasis (cM1). These findings suggest that NLR, a simple and cost-effective biomarker, may provide valuable prognostic information complementary to conventional staging systems. Integration of NLR into prognostic models may enhance risk stratification and guide personalized treatment approaches in kidney cancer management. Further prospective studies are warranted to validate these findings and explore the potential utility of NLR in clinical decision-making.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.