Significance of Pathologic T3a Upstaging in Clinical T1 Renal Masses Undergoing Nephrectomy

doi:10.1016/j.clgc.2015.01.001

Clinical Genitourinary Cancer

Volume 13, Issue 4, August 2015, Pages 344-349

https://doi.org/10.1016/j.clgc.2015.01.001 Get rights and content

Abstract

Background

The objectives of the present study were to report the incidence of pathologic T3a upstaging in a contemporary cohort of patients with clinical stage T1 (cT1) renal tumors treated with partial or radical nephrectomy; investigate the clinical outcomes; and identify the predictors associated with pathologic upstaging.

Materials and Methods

From a single-institution, institutional review board–approved renal tumor database of 945 patients, we identified 610 patients who had undergone surgery for a cT1 renal mass. Data for 494 patients were available for analysis. Of these, 66 lesions had been pathologically upstaged to T3a after surgery and 428 had not. The oncologic follow-up data and clinical and pathologic features were recorded, and multivariable logistic regression analysis was performed to identify the risk factors for pT3a upstaging, controlling for age, gender, body mass index, and nephrectomy type.

Results

The cT1 tumors of 66 patients (13.3%) were upstaged to pT3a after surgery. Of these 66 patients, 44 (66.7%) had undergone partial and 22 (33.3%) radical nephrectomy. The median follow-up period was 50 months. No patient with upstaging developed recurrence, and all were disease free at their last follow-up visit. On multivariable analysis, tumor size > 4 cm (odds ratio [OR], 3.766; 95% confidence interval [CI], 1.417-10.011; P < .008), clear cell histologic features (OR, 4.461; 95% CI, 1.498-13.461; P < .007), and positive surgical margins (hazard ratio, 5.118; 95% CI, 2.088-12.547; P < .0001) were associated with upstaging.

Conclusion

Of the cT1 lesions in 66 patients, 13% were pathologically upstaged after surgery. The patients with larger tumors, clear cell histologic features, and positive surgical margins were at the greatest risk of upstaging. However, after an intermediate follow-up period, pathologic upstaging did not appear to result in worsened oncologic outcomes.

Introduction

The incidence of renal cell carcinoma (RCC) is increasing, in part because of the increasing use of cross-sectional imaging. Most renal cortical tumors are now incidentally detected as small masses in asymptomatic patients.¹ The vast majority of these masses will be ≤ 7 cm, or clinical stage T1 (cT1) masses. Traditionally, radical nephrectomy (RN) has been the reference standard for the surgical management of these renal masses. However, with evidence demonstrating equivalent oncologic outcomes and improved nononcologic outcomes with renal preservation, treatment has shifted toward partial nephrectomy (PN) for cT1 renal tumors.2, 3 Subsequently, an increase has also occurred in the number of tumors found to have occult adverse pathologic features, with upstaging, after surgical excision, to pathologic T3a (pT3a) using the 2010 “American Joint Committee on Cancer Tumor Necrosis and Metastasis, 7th edition.”⁴ The 2010 edition has grouped tumors with adverse pathologic features such as sinus fat invasion (SFI), renal vein and muscular branch invasion (RVI)—without inferior vena cava invasion—and perinephric fat invasion (PFI) into the pT3a category, regardless of the tumor size. The objectives of the present study were to report the incidence of pT3a upstaging in a contemporary cohort of patients with cT1 renal tumors who had undergone PN or RN at a high-volume academic center, investigate the clinical outcomes of the patients with pathologically upstaged cT1 tumors, and identify the predictors associated with pathologic upstaging.

Section snippets

Materials and Methods

An institutional review board–approved prospectively collected database was retrospectively reviewed for patients who had undergone nephrectomy at New York University Langone Medical Center from 1997 to 2012 for RCC. The study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All the patients had given written informed consent when originally enrolled in the database. From a total of 945 patients in the database, 610

Results

In our cohort of 494 patients, who had undergone either PN or RN for cT1 RCC, the lesions of 66 (13.3%) were upstaged to pT3a after surgery. A subset analysis of our PN cohort showed a 10.4% upstaging rate (44 of 422). Of the 66 patients in group 1, 44 (66.7%) had undergone PN and 22 (33.3%) RN. The demographic data are summarized in Table 1. The median follow-up period for group 1 was 50 months (range, 1-122 months) and the median follow-up period for group 2 was 52.5 months (range, 1-110

Discussion

The incidence, clinical characteristics, and outcomes of the patients with cT1 renal masses with occult pathologic stage T3a diagnosed after surgical excision has not been widely reported. In our cohort of 494 patients, 66 (13.3%) had their lesions upstaged to pT3a. We included patients undergoing both PN and RN in our analysis; however, the subanalysis of our PN cohort still showed a 10.4% upstaging rate. This was greater than the rate recently reported by Gorin et al⁶ in their analysis of cT1

Conclusion

In our contemporary cohort of patients, approximately 13% of patients with cT1 tumors who had undergone surgery had their tumor pathologically upstaged to T3a after surgery. An increasing tumor size > 4 cm, CC, and PSM predicted upstaging to pT3a after nephrectomy. With a median follow-up period of ≥ 50 months, of the patients with a cT1 tumor who had undergone nephrectomy and had occult pT3a tumor upstaging, none had developed locally recurrent or metastatic disease. We have provided some

Disclosure

The authors have stated that they have no conflicts of interest.

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Cited by (44)

The preoperative predictive factors for pathological T3a upstaging and positive surgical margin of clinical T1 renal cell carcinoma
2024, Actas Urologicas Espanolas
El objetivo del presente estudio es establecer parámetros que permitan predecir la afectación de los márgenes quirúrgicos positivos (MQP) y la elevación de estadio clínico T1 (cT1) a estadio patológico T3a (pT3a) en personas con carcinoma de células renales (CCR).
Un total de 159 individuos fueron sometidos a nefrectomía radical (NR) o nefrectomía parcial (NP) por CCR. En el periodo preoperatorio, se evaluaron los datos demográficos, los hallazgos de laboratorio y los resultados radiológicos y anatomopatológicos que podían ser factores predictores de MQP y del incremento a estadio pT3a. Las variables categóricas y continuas se compararon entre los grupos de pacientes con o sin MQP y/o incremento a estadio pT3a mediante la prueba X² de Pearson y la t de Student de muestras independientes o la U de Mann-Whitney, respectivamente.
Se detectó un aumento a estadio pT3a en 32 (20,1%) sujetos, y MQP en 28 (17,6%). De los pacientes reestadificados a pT3, 27 fueron sometidos a cirugía abierta y cinco a laparoscópica (p < 0,001). Además, de las personas reestadificadas a pT3a, a seis se les realizó una NR y a 26 una NP (p < 0,001). El grosor del tejido adiposo peritumoral fue de 11,97 y 15,38 en los grupos con estadio patológico T1 (pT1) y pT3a, respectivamente (p = 0,022). En aquellos con un aumento a estadio pT3a tenían un tamaño del tumor mayor, y la puntuación del RENAL nephrometry score (RNS) y el índice de inmunidad-inflamación sistémica (IIS) eran más elevados (p < 0,001 y p < 0,001 y p = 0,022,). Se determinó que la relación aspartato transaminasa/alanina transaminasa (AST/ALT) (índice De Ritis ratio [DRR]) y la relación albúmina/fosfatasa alcalina (A/FA) tenían un valor pronóstico significativo en la predicción de MQP (p = 0,024, y p = 0,001, respectivamente). Según el análisis de las características operativas del receptor (ROC), el tamaño del tumor predijo el incremento a estadio a pT3a con una sensibilidad de 100% y una especificidad de 98,6% cuando su valor de corte fue de 6,85 mm (área bajo la curva [AUC]: 1,000, p < 0,001). Además, el análisis de regresión logística reveló que A/FA y DRR eran predictores significativos de MQP (p < 0,001, y p = 0,009).
Los resultados de este estudio indicaron que la técnica quirúrgica elegida y el tipo de intervención, el tamaño del tumor, el valor de RNS, el grosor del tejido adiposo peritumoral, las unidades Hounsfield (UH) del tejido adiposo peritumoral y perirrenal, y los valores de DRR e IIS pueden anticipar el incremento de estadio cT1 a pT3a en los pacientes con CCR, y que los valores de A/FA y DRR pueden predecir los MQP.
The objective of this study is predict positive surgical margin (PSM) and pathological T3a (pT3a) upstaging in patients with clinical T1 (cT1) renal cell carcinoma (RCC).
159 patients who underwent radical nephrectomy (RN) or partial nephrectomy (PN) for RCC. Patients’ demographic, laboratory, radiological and pathological data that could predict PSM and pT3a upstaging pre-operatively were evaluated. The categorical and continuous variables were compared between the patient groups with or without PSM and/or pT3a upstaging using Pearson's chi-square test, and independent samples t-test or the Mann-Whitney U test, respectively.
PT3a upstaging was detected in 32 (20.1%) patients, and PSM was detected in 28 (17.6%) patients. PT3a upstaging was detected in 27 and 5 patients who underwent open surgery and laparoscopic surgery, respectively (p < 0.001). In addition, pT3a upstaging was detected in 6 and 26 patients who underwent RN and PN, respectively (p < 0.001). Peritumoral fatty tissue thickness was 11.97 and 15.38 in the pT1 and pT3a patient groups, respectively (p = 0.022). In patients with pT3a upstaging, tumor size was larger, and renal nephrometry score and systemic immune-inflammation index (SII) were higher (p < 0.001, p < 0.001, and p = 0.022, respectively). It was determined that De Ritis ratio (DRR) and albumin-to-alkaline phosphatase (ALP) ratio (AAPR) parameters had significant prognostic values in predicting PSM (p = 0.024, and p = 0.001, respectively). ROC analysis indicated that tumor size predicted pT3a upstaging with 100% sensitivity and 98.6% specificity when its cut-off value was taken as 6.85 mm (AUC: 1.000, p < 0.001). In addition, logistic regression analysis revealed AAPR and DRR as significant predictors of PSM (p < 0.001, and p = 0.009, respectively).
The findings of this study indicated that the surgical technique of choice and the type of operation, tumor size, RNS value, peritumoral fatty tissue thickness, HU values of peritumoral and tumor side fatty tissues, and DRR and SII values can predict pT3a upstaging of patients with cT1 RCC, and that AAPR and DRR values can predict PSM.
Adverse pathologic features impact survival outcomes for small renal masses following nephrectomy
2023, Urologic Oncology: Seminars and Original Investigations
While most small renal masses (SRM) < 4 cm have an excellent prognosis following resection, the impact of adverse T3a pathologic features on oncologic outcomes of SRMs remains unclear. We sought to compare clinical outcomes for surgically resected pT3a versus pT1a SRMs at our institution.
We retrospectively reviewed records of patients who underwent radical or partial nephrectomy (RN, PN) for renal tumors <4 cm at our institution between 2010 and 2020. We compared features and outcomes of pT3a vs pT1a SRMs. Continuous and categorical variables were compared using Student's t and Pearson's chi-squared tests, respectively. Postoperative outcomes of interest including overall, cancer-specific, and recurrence-free survival (OS, CSS, and RFS) were analyzed using Kaplan-Meier method, Cox proportional hazard regression, and competing risk analysis. Analyses were performed using R statistical package (R Foundation, v4.0).
We identified 1,837 patients with malignant SRMs. Predictors of postoperative pT3a upstaging included higher renal score, larger tumor size, and presence of radiologic features concerning for T3a disease (odds ratio [OR] = 5.45, 95% confidence interval [CI] 3.92–7.59, P < 0.001). On univariable modeling, pT3a SRMs had higher positive margin rates (9.6% vs 4.1%, P < 0.001), worse OS (hazard ratio [HR] = 2.9, 95% CI 1.6-5.3, P = 0.002), RFS (HR 9.32, 95% CI 2-40.1, P = 0.003), and CSS (HR = 3.6, 95% CI 1.5–8.2, P = 0.003). On multivariable modeling, pT3a status remained associated with worse RFS (HR = 2.7, 95% CI 1.04–7, P = 0.04), but not OS (HR 1.6, 95% CI = 0.83–3.1, P = 0.2); multivariable modeling was deferred for CSS due to low event rates.
Adverse T3a pathologic features portend worse outcomes for SRMs, highlighting the crucial role of pre-operative planning and case selection. These patients have relatively poor prognosis, and should be monitored more closely and counseled for consideration of adjuvant therapy or clinical trials.
Partial versus radical nephrectomy for the treatment of pT3aN0M0 renal cell carcinoma: A propensity score analysis
2023, Asian Journal of Surgery
The survival benefit of partial nephrectomy (PN) in pT3a RCC patients is controversial. Here we aimed to explore the potential benefit of PN for pT3aN0M0 renal cell carcinoma (RCC).
Data of patients with pT3aN0M0 RCC who were diagnosed between 2010 and 2012 in the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database were retrospectively collected. Overall survival (OS) and cancer specific survival (CSS) were compared using a Cox proportional hazards model between PN and radical nephrectomy (RN) in pT3aN0M0 RCC. Propensity score (–adjusted, –stratified, –weighted, and –matched) analyses were performed to control for imbalances in individual risk factors.
A total of 1277 patients with pT3aN0M0 RCC were identified, of whom 200 patients were treated with PN and 1077 patients were RN. PN showed favorable OS and CSS in 0–4 cm pT3aN0M0 RCC (P < 0.05), and similar OS and CSS in 4–7 cm pT3aN0M0 RCC, compared with RN using un-adjusted analyses. The Propensity score analyses further demonstrated the survival benefit of PN compared with the RN in 0–4 cm pT3aN0M0 RCC (P < 0.05).
In this retrospective study, PN was associated with improved survival compared with RN in 0–4 cm pT3aN0M0 RCC. Moreover, survival was comparable between PN and RN in 4–7 cm pT3aN0M0 RCC. These data provided evidence that PN could be an alternative choice for T3aN0M0 RCC less than 7 cm. Particularly, patients with 0–4 cm pT3aN0M0 RCC might benefit from PN.
Predictive value of renal tumor contour irregularity score in pathological T3a upstaging of clinical T1 renal cell carcinoma: A multi-institutional study
2022, Urologic Oncology: Seminars and Original Investigations
Citation Excerpt :
With the development of surgical techniques, PN is gradually used in patients with T1b renal cell carcinoma (RCC) [5,6]. However, about 4.1% to 13.3% of patients with cT1 RCC will be upgraded to pT3a stage [7–13]. The prognosis of patients with pT3a upstaging is significantly worse than that of other patients without pathological upstaging [14–16].
To explore the predictive value of renal tumor contour irregular degree (CID) in pathological T3a upstaging of clinical T1 renal cell carcinoma (RCC).
We performed a retrospective multi-institutional review of 1,487 patients with clinical T1N0M0 RCC between January 2009 and June 2019. Kaplan-Meier survival curve and Cox regressions were used to analyze the prognostic factors of disease-free survival (DFS). Logistic regressions were performed to determine predictors of pathological T3a upstaging in clinical T1 RCC.
Among 1,487 patients with cT1 RCC, 96 (6.5%) were pathological T3a upstaging. Multivariable logistic regression analysis showed that age (odds ratio [OR] = 1.022, 95% confidence interval [CI] = 1.001–1.042, P = 0.036), tumor maximum diameter(OR = 1.242, 95% CI = 1.042-–1.480, P = 0.015) and CID (OR = 1.067, 95% CI = 1.051–1.083, P < 0.001) were independent predictors of pathological T3a upstaging. The area under the curve (AUC) of the prediction model that included the CID was 0.846, while the AUC of the prediction model that did not include CID was only 0.741, the difference was statistically significant (P < 0.001). Kaplan-Meier survival curve showed that patients with pathological T3a upstaging had significantly worse DFS than patients without pathological T3a upstaging (P < 0.001). Multivariable Cox analysis showed that pathological T3a upstaging (HR = 1.836, 95% CI = 1.013–3.329, P = 0.002) is an independent prognostic factor for DFS in patients with cT1N0M0 RCC.
The predictive model of CID combined with tumor maximum diameter and age significantly improved the ability to predict pathological T3a upstaging in clinical T1 RCC, compared with the prediction model of tumor maximum diameter combined with age. The predictive model of CID combined with tumor maximum diameter and age may be applicable to patients considering partial vs. radical nephrectomy.
Upstaging to pT3a in Patients Undergoing Partial or Radical Nephrectomy for cT1 Renal Tumors: A Systematic Review and Meta-analysis of Outcomes and Predictive Factors
2021, European Urology Focus
Predictors of upstaging from cT1 to pT3a renal masses are poorly inquired, and this remains an area of controversial findings.
To evaluate predictors and outcomes of upstaging from cT1 to pT3a in patients undergoing surgical removal of a renal tumor.
A systematic literature search was performed to identify relevant articles using three electronic engines (PubMed, Embase, and Web of Science). Only studies looking at upstaging to pT3a in patients undergoing either partial nephrectomy (PN) or radical nephrectomy (RN) for cT1 renal tumor were included. Study selection was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement.
Thirteen studies, including 21869 patients (cT1/pT3a: 1256 [5.7%]; cT1/pT1: 20613 [93.3%]), were identified. Patients in the upstaged group were older (weighted mean difference [WMD]: 3.89; p < 0.00001) and mostly male (odds ratio [OR]: 1.23; p = 0.04). Renal tumors were larger (WMD: 0.98; p < 0.00001), more complex (OR: 2.38; p < 0.0001), and with a higher rate of cT1b masses (OR: 3.36; p < 0.00001). The cT1/pT3a group had a higher rate of other renal cell carcinoma histological subtypes (OR: 1.59; p = 0.04), as well as higher odds of Fuhrman grade ≥3 (OR: 2.57; p < 0.00001) and positive surgical margins (OR: 1.85; p = 0.007). Five-year recurrence-free survival (RFS) was worse in the upstaged group (OR: 0.31; p = 0.02). Age (OR: 1.03; p < 0.00001), tumor size (OR: 1.51; p < 0.00001), and RENAL score (OR: 2.80; p = 0.0004) were predictors of upstaging. Upstaging was associated with overall survival (hazard ratio [HR]: 1.94; p = 0.05), cancer-specific survival (HR: 2.24; p = 0.007), and RFS (HR: 2.17; p < 0.00001).
Upstaging to pT3a in case of surgical removal of a cT1 renal tumor is an uncommon event, which however can translate into worse oncological outcomes. Both patient (older age) and tumor (larger size and higher complexity) characteristics are associated with a higher risk of upstaging. There is very limited evidence regarding whether RN would be better than PN in these cases. There remains an unmet need for tools to better characterize renal masses in the preoperative setting.
About 6% of surgically treated localized renal tumors can be found to be locally advanced on final pathology after surgery. This “upstaging” can translate into worse oncological outcomes. There are patient and tumor characteristics that are associated with an increased the risk of upstaging.
Does renal tumor biopsies for small renal carcinoma increase the risk of upstaging on final surgery pathology report and the risk of recurrence?
2020, Urologic Oncology: Seminars and Original Investigations
Citation Excerpt :
Our study confirms that tumor upstaging from cT1a to pT3a is infrequent, with 6.5% of patients from our cohort having experienced such an event. This upstaging rate is similar to what has previously been reported in the literature with most studies reporting risks of <10%, although higher rates have also been reported [22–30]. Importantly, and contrary to the 2 previously mentioned studies, our large multi-institution Canadian cohort failed to support an association between RTB and upstaging to pT3a.
Renal tumor biopsies (RTB) have been proposed as a means to diminish overtreatment of small renal masses. A potential concern of RTB is tumor seeding along the biopsy tract leading to worse clinical outcomes.
To evaluate whether RTB was associated with greater upstaging to pT3a compared to patients without a biopsy and to determine if pathologic upstaging affects the risk of recurrence.
The Canadian Kidney Cancer information system was used to identify patients who underwent radical or partial nephrectomy for malignant renal tumors ≤ 4cm (cT1a) between January 1, 2011 and July 2, 2019.
RTB prior to nephrectomy or nephrectomy without biopsy.
Upstaging to pT3a and cancer recurrence were compared between subjects that had a RTB compared to those who did not. A multivariable analysis was used to evaluate factors associated with disease upstaging and recurrence.
The cohort consisted of 1993 cT1a patients, followed for a median of 17.5 months. Of these patients, 502 (25%) had a preoperative RTB. There was no difference in the proportion with tumor upstaging to pT3a between patients that had RTB compared to those who did not (7.2% vs. 6.3%; P = 0.5). On multivariable analysis, RTB was not associated with pathological upstaging (Odds Ratio 0.90; 95% Confidence Interval 0.61–1.34) or recurrence (Odds Ratio 1.04; 95% Confidence Interval 0.57–1.89). The main limitation is that the study is underpowered to detect small differences between groups.
In this large, multi-institution cohort, RTB was not associated with increased risk of tumor upstaging or recurrence. Hence, tumor tract seeding, although possible, should not be a clinical deterrent to using RTBs as a means of personalizing renal masses management and diminishing overtreatment.
Recent evidence suggests that tumor seeding following RTB may be more common than initially perceived. Our results have demonstrated that RTB was not associated with an increased risk of tumor upstaging or disease recurrence.

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Original StudySignificance of Pathologic T3a Upstaging in Clinical T1 Renal Masses Undergoing Nephrectomy

Abstract

Background

Materials and Methods

Results

Conclusion

Introduction

Section snippets

Materials and Methods

Results

Discussion

Conclusion

Disclosure

Urology

J Urol

J Urol

J Urol

J Urol

J Urol

Eur Urol

J Urol

J Urol

J Urol

Urology

J Urol

J Urol

Eur Urol

J Urol

Clin Genitourin Cancer

Original Study
Significance of Pathologic T3a Upstaging in Clinical T1 Renal Masses Undergoing Nephrectomy