Number of metastatic sites rather than location dictates overall survival of patients with node-negative metastatic renal cell carcinoma

doi:10.1016/S0090-4295(02)02163-5

Urology

Volume 61, Issue 2, February 2003, Pages 314-319

https://doi.org/10.1016/S0090-4295(02)02163-5 Get rights and content

Abstract

Objectives

To perform a retrospective study to determine whether survival and immunotherapy response are related to the site of metastases (lung versus bone) and to the number of organ sites involved (one versus multiple). The most common sites of metastatic renal cell carcinoma (mRCC) are the lung and bone.

Methods

The records of 434 patients with mRCC were reviewed. Patients with pathologic evidence of nodal involvement were excluded, leaving 120 patients with mRCC to lung only, 33 patients to bone only, and 144 patients with multiple organ involvement. The response rates to immunotherapy and overall survival were compared. The variables evaluated in statistical analyses included Eastern Cooperative Oncology Group score, grade, 1997 tumor stage, and multiple organ involvement.

Results

The median survival for patients with lung only and bone only mRCC was 27 months; patients with multiple organ involvement had a median survival of 11 months. In patients who underwent nephrectomy followed by immunotherapy, the median survival time was 31, 31, and 13 months in the lung, bone, and multiple sites groups, respectively. The response rate to immunotherapy after nephrectomy was 44%, 20%, and 14% in the lung, bone, and multiple organ groups, respectively. Multivariate analysis confirmed that metastatic disease to more than one organ site was associated with poor prognosis (2.05 risk ratio, P <0.001).

Conclusions

Patients with mRCC to only one organ site fared significantly better than patients who had evidence of disease in multiple organs. Survival in patients with disease limited to the lung was similar to that of patients whose disease was limited to bone.

Section snippets

Patient population

The records of 1087 patients treated at University of California, Los Angeles (UCLA) between 1989 and 2000 were reviewed, identifying 434 patients with mRCC. Patients with pathologic evidence of nodal disease were eliminated from comparison purposes because these patients do poorly regardless of treatment, leaving 297 patients available for evaluation. Three groups of patients who presented with metastases at the time of diagnosis were defined. Metastatic lesions to lung only were present in

Results

The mean age in each of the groups was 59.6 years (lung), 61.1 years (bone), and 57.5 years (multiple). The proportion of men was 78% in the lung group, 81% in the bone group, and 69% in the multiple organ group.

Table I summarizes the presentation characteristics of the three groups. Approximately 55% of the patients had T3 tumors. However, 16% of the primary tumors in the multiple organ group were Stage T4 compared with 7% and 4% in the lung only and bone only groups (P = 0.019), respectively.

Comment

The inclusion of prognostic factors in the analysis of survival data in patients with mRCC is of known importance. Motzer et al.15 recently reported that low Karnofsky score, increased lactate dehydrogenase and calcium levels, absence of nephrectomy, and development of anemia stratified patients into favorable-risk, intermediate-risk, and poor-risk groups with regard to prognosis.

In terms of site or number of metastatic deposits, recent investigators have reported conflicting results on whether

References (24)

R.A. Figlin
Renal cell carcinomamanagement of advanced disease
J Urol
(1999)
S. Mani et al.
Prognostic factors for survival in patients with metastatic renal cancer treated with biological response modifiers
J Urol
(1995)
J.C. Nesbitt et al.
Surgical management of renal cell carcinoma with inferior vena cava tumor thrombus
Ann Thorac Surg
(1997)
P.A. Palmer et al.
Prognostic factors for survival in patients with advanced renal cell carcinoma treated with recombinant interleukin-2
Ann Oncol
(1992)
G.H. Mickisch et al.
Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinomaa randomised trial
Lancet
(2001)
A. Jemal et al.
Cancer statistics, 2002
CA Cancer J Clin
(2002)
R.J. Motzer et al.
Renal-cell carcinoma
N Engl J Med
(1996)
B. Ljungberg et al.
Factors of importance for prediction of survival in patients with metastatic renal cell carcinoma, treated with or without nephrectomy
Scand J Urol Nephrol
(2000)
M.A. Kuczyk et al.
Prognostic relevance of intracaval neoplastic extension for patients with renal cell cancer
Br J Urol
(1997)
A.J. Pantuck et al.
Regional lymphadenopathy during cytoreductive nephrectomy predicts IL-2 failure in patients with metastatic renal cell carcinoma
Proc ASCO
(2001)

H.B. Tongaonkar et al.

Renal cell carcinoma extending to the renal vein and inferior vena cavaresults of surgical treatment and prognostic factors

J Surg Oncol

(1995)

S.A. Fuhrman et al.

Prognostic significance of morphologic parameters in renal cell carcinoma

Am J Surg Pathol

(1982)

Cited by (109)

Prognostic Significance of Radiographic Lymph Node Invasion in Contemporary Metastatic Renal Cell Carcinoma Patients
2024, Clinical Genitourinary Cancer
To test the prognostic significance of radiographic cN-stage in metastatic renal cell carcinoma (mRCC) patients with low metastatic burden (1 site of metastasis), relying on the Surveillance, Epidemiology, and End Results database (SEER 2010-2020).
Included were mRCC patients with 1 site of metastasis, treated with systemic therapy without cytoreductive nephrectomy (CN). Kaplan-Meier plots and multivariable Cox-regression models addressed cancer-specific mortality (CSM) according to radiographic cN-stage (ccN1 vs. ccN0). Separate subgroup analyses were performed, addressing radiographic N-stage in patients with distinct histology (clear-cell vs. RCC not otherwise specified [RCC NOS]).
Of 1756 mRCC patients, 545 (31%) were radiographic cN1. Overall, the median CSM-free survival of the cohort was 11 months. Median CSM-free survival was 8 vs. 14 months in radiographic cN1 vs. cN0 mRCC patients (HR 1.49, P < .0001). In multivariable Cox regression analyses, radiographic cN1 status was an independent predictor of higher CSM (HR 1.39; P = .01). In subgroup analyses, addressing patients with clear-cell histology and patients with RCC NOS separately, radiographic cN1 status remained independently associated with a higher CSM in both groups (clear-cell: HR 1.36; P = .03; RCC NOS: HR 2.06; P = .009).
In mRCC patients with low metastatic burden, presence or absence of radiographic lymph node invasion results in a clinically meaningful discrimination between those with poor prognosis and others. In consequence, consideration of radiographic lymph node invasion might be of great value in this specific population of mRCC patients.
Survival of patients with clear cell renal carcinoma according to number and location of organ-specific metastatic sites
2024, Urologic Oncology: Seminars and Original Investigations
The prognostic significance of number and location of organ-specific metastatic sites in treated metastatic clear cell renal carcinoma (ccmRCC) patients is object of debate. The current study aimed to test the association between number and location of organ-specific metastatic sites and overall survival (OS) in ccmRCC.
Within Surveillance, Epidemiology and End Results database (2010–2018), all ccmRCC patients treated with cytoreductive nephrectomy and/or systemic therapy were identified. Kaplan-Meier plots and Cox regression models focused on: A). number of organ-specific metastatic sites: solitary vs. 2 vs. 3 or more; B). solitary organ-specific metastatic sites (lung vs. bone vs. liver vs. brain); C). combinations of 2 and 3 or more different organ-specific metastatic sites.
Of 4,527 patients (median OS: 19 months), 3,054 (67%) harbored solitary organ-specific metastatic sites (27 months) vs. 1,153 (25%) combinations of 2 different organ-specific metastatic sites (12 months) vs. 320 (8%) combinations of 3 or more different organ-specific metastatic sites (7 months). In patients with solitary organ-specific metastatic sites, bone metastases portended the longest median OS (median OS: 31 months) vs. liver metastases portended the shortest median OS (16 months). Both were independent predictors of OS (multivariable hazard ratio, bone: 0.87; liver: 1.21). Median OS was similarly poor in patients with combinations of 2 different organ-specific metastatic sites (9–13 months), regardless of their location. The same pattern applied to patients with combinations of 3 or more different organ-specific metastatic sites (6–7 months).
Solitary organ-specific metastatic sites portend the most favorable OS (16–31 months). Solitary bone metastases yield the longest vs. liver metastases the shortest OS. Invariably poor OS applies to combinations of 2 (9–13 months), as well as 3 or more different organ-specific metastatic sites (6–7 months), regardless of their location.
The Evolving Role of Metastasectomy for Patients with Metastatic Renal Cell Carcinoma
2020, Urologic Clinics of North America
Long-term Outcomes of Follow-up for Initially Localised Clear Cell Renal Cell Carcinoma: RECUR Database Analysis
2019, European Urology Focus
Optimal follow-up (FU) strategy to detect potentially curable (PC) recurrences after treatment of localised clear cell renal cell carcinoma (ccRCC) is unclear. This study retrospectively analysed a large international database to determine recurrence patterns and overall survival (OS), as part of a wider project to issue recommendations on FU protocols.
To analyse associations between RCC recurrences in patients with ccRCC, their risk group stratifications, treatments, and subsequent outcomes.
Nonmetastatic ccRCC patients treated with curative intent between 1 January 2006 and 31 December 2011, with at least 4 yr of FU, were included. Patient, tumour and recurrence characteristics, Leibovich score, and management and survival data were recorded. Isolated local, solitary, and oligometastatic (three or fewer lesions at a single site) recurrences were considered PC, while all others were probably incurable (PI).
Primarily curative surgical treatment of ccRCC while at recurrence detection metastasectomy, systemic therapy, best supportive care, or observation.
Incidence, time to recurrence (TTR), and OS were measured. Competing risk analysis, Kaplan-Meier, and Cox regression models were used.
Of 1265 patients with ccRCC, 286 had a recurrence, with 131 being PC and 155 PI. Five-year cumulative risks of recurrence for low- (n = 53), intermediate- (n = 105), and high-risk (n = 128) patients were, respectively, 7.2%, 23.2%, and 61.6%, of whom 52.8%, 37.1%, and 30.5% were PC, respectively. Median TTR was 25.0 for PC patients versus 17.3 mo for PI patients (p = 0.004). Median OS was longer in PC compared with that in PI patients (p < 0.001). Competing risk analysis showed highest risk of ccRCC-related death in younger and high-risk patients. Limitations were no data on comorbidities, retrospective cohort, and insufficient data excluding 12% of cohort.
Low-risk group recurrences are rare and develop later. Treatment of recurrences with curative intent is disappointing, especially in high-risk patients. An age- and risk score-dependent FU approach is suggested.
We analysed data from eight European countries, and found that the incidence of the kidney cancer recurrence and patient survival correlated with clinical factors known to predict cancer recurrence reliably and age. We conclude that these factors should be used to design follow-up strategies.
Impact of synchronous metastasis distribution on cancer specific survival in renal cell carcinoma after radical nephrectomy with tumor thrombectomy
2015, Journal of Urology
Metastatic renal cell carcinoma can be clinically diverse in terms of the pattern of metastatic disease and response to treatment. We studied the impact of metastasis and location on cancer specific survival.
The records of 2,017 patients with renal cell cancer and tumor thrombus who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 centers in the United States and Europe were analyzed. Number and location of synchronous metastases were compared with respect to patient cancer specific survival. Multivariable Cox regression models were used to quantify the impact of covariates.
Lymph node metastasis (155) or distant metastasis (725) was present in 880 (44%) patients. Of the patients with distant disease 385 (53%) had an isolated metastasis. The 5-year cancer specific survival was 51.3% (95% CI 48.6–53.9) for the entire group. On univariable analysis patients with isolated lymph node metastasis had a significantly worse cancer specific survival than those with a solitary distant metastasis. The location of distant metastasis did not have any significant effect on cancer specific survival. On multivariable analysis the presence of lymph node metastasis, isolated distant metastasis and multiple distant metastases were independently associated with cancer specific survival. Moreover higher tumor thrombus level, papillary histology and the use of postoperative systemic therapy were independently associated with worse cancer specific survival.
In our multi-institutional series of patients with renal cell cancer who underwent radical nephrectomy and tumor thrombectomy, almost half of the patients had synchronous lymph node or distant organ metastasis. Survival was superior in patients with solitary distant metastasis compared to isolated lymph node disease.
Surgical treatment for pelvic bone metastatic disease from renal cell carcinoma
2023, Journal of Surgical Oncology

View all citing articles on Scopus

View full text

Adult urologyNumber of metastatic sites rather than location dictates overall survival of patients with node-negative metastatic renal cell carcinoma

Abstract

Objectives

Methods

Results

Conclusions

Section snippets

Patient population

Results

Comment

J Urol

J Urol

Ann Thorac Surg

Ann Oncol

Lancet

Cancer statistics, 2002

CA Cancer J Clin

Renal-cell carcinoma

N Engl J Med

Factors of importance for prediction of survival in patients with metastatic renal cell carcinoma, treated with or without nephrectomy

Scand J Urol Nephrol

Prognostic relevance of intracaval neoplastic extension for patients with renal cell cancer

Br J Urol

Regional lymphadenopathy during cytoreductive nephrectomy predicts IL-2 failure in patients with metastatic renal cell carcinoma

Proc ASCO

Renal cell carcinoma extending to the renal vein and inferior vena cavaresults of surgical treatment and prognostic factors

J Surg Oncol

Prognostic significance of morphologic parameters in renal cell carcinoma

Am J Surg Pathol

Adult urology
Number of metastatic sites rather than location dictates overall survival of patients with node-negative metastatic renal cell carcinoma