Objective:The incidence of renal cell carcinoma (RCC) is rising in part due to small tumors (≤4cm) detected incidentally with abdominal imaging. Survival for small RCCs has been regarded as favorable and guidelines recommend partial rather than total nephrecteomy. We studied the frequency of synchronous metastasis in patients with small RCCs in Iceland.

Materials and methods: A retrospective study on 257 patients with RCC ≤4cm out of 1102 RCC patients diagnosed in Iceland 1971-2010. Patients with metastasis were compared to those with localized disease. Hospital charts were reviewed and histology, TNM-stage and disease-specific survival compared between groups.

Results: The proportion of small tumors increased from 9% in 1971-1980 to 33% in 2001-2010 (p<0,001) and incidental detection increased from 14% to 39% during the same period. Out of the 257 patients with small RCCs, 25 (10%) had synchronous metastases, most frequently in lungs or bones. Patients with metastases were on average 1.9 years older, their tumors were 0.2 cm larger and more often located in the right kidney, their hemoglobin was lower and nuclear grade and T-stage higher. Histology was similar in both groups. Five-year survival of patients with and without metastases was 7 vs. 94%, respectively (p<0.001).

Conclusions: One out of ten patients with small RCC has synchronous metastases at diagnosis. This is higher than in most previous reports that usually include surgical patients only. Patients with metastases are significantly older, more often symptomatic, their tumor are larger and their prognosis worse. Our results indicate that small RCC is a potentially systemic disease at diagnosis that has to be taken seriously.

Gudjonsson PS¹, Mariusdottir E³, Palsdottir HB ³, Jonsson E², Petursdottir V³, Hardarson S³, Sigurdsson MI², Gudbjartsson T^1,2

¹Faculty of Medicine, University of Iceland, Departments of  ²Urology and ²Surgery, ³Department of Pathology, Landspítali University hospital.

 

Table I. Localization of synchronous metastasis in 25 patients with small RCC (≤4 cm) in Iceland 1971-2010. Metastasis can occur simultaneously in multiple organs.

Localisation	n (%)
Lung	12 (48)
Bone	10 (40)
Liver	8 (32)
Brain	2 (8)
Lymph nodes	8 (32)
Other organs	11 (44)

 

Table II. Symptoms in patients that were diagnosed with small RCCs (≤4 cm), comparing those with synchronous metastasis (n=21) and patients with localized disease (n=90). Incidentally diagnosed patients in both groups are excluded (4 and 142 patients, respectively). Patients can have more than one symptom.

Symptoms	Synchronous mets n=21	Localized RCC n=90
Abdominal pain	8 (38)	52(58)
Weight loss	6 (29)	16 (18)
Macroscopic hematuria	2 (10)	33 (37)
Anemia	2 (10)	7 (8)
Hypertension	1 (5)	2 (2)
Fever	0 (0)	6 (7)
Erythrocytosis	0 (0)	1 (1)
Symptoms due to distant metastasis	13 (62)	-
Other symptoms	7 (33)	18 (20)

 

Table III. Clincopathological parameters in patients with small RCC (≤4 cm), comparing those that were diagnosed with or without synchronous metastases.

	Synchronous mets n = 25	Localized RCC n = 232	p-value
Age, yrs, stdv. (range)	66 ±13 (33-82)	64 ±12 (23-96)	0.009
Male/female ratio	1,1	1,3	0.76
Tumor size, cm, stdv. (range)	3,1 ± 0,7 (1,8-4,0)	2,9  ± 0,8 (0,3-4,0)	0.03
Kidney Right
	12 (48)	140 (60)	0.29
Left	13 (52)	92 (40)
Hemoglobin, g/L, stdv. (range)	122 ± 19 g/L (75-155)	138 ± 18  g/L  (80-220)	0.04
Grade*
1+2	8 (40)	190 (85)	< 0.001
3+4	12 (60)	34 (15)
T-stage**
T1a	11 (46)	204 (88)	< 0.001
T3-4	13 (54)	27 (12)
Histology***
Clear cell	19 (86)	200 (88)	0.6
Papillary	2 (9)	22 (10)
Chromophobe	1 (5)	5 (2)
Surgery
Nephrectomy	9 (36)	198 (85)	< 0.001
Partial nephrectomy	0	25 (11)
No surgery	16 (64)	9 (4)

*Information on nuclear grade missing for 13 patients, **Information for T-stage missing for 2 patients,***Information on histology was missing for 8 patients.

Figure 1. Proportion of patients with small RCCs (≤4 cm) of all patients (both genders together) that were diagnosed with RCC in Iceland in 10 year periods between 1971 and 2010. The proportion of incidentally detected RCCs of any size is also shown.

Figure 2.  Disease-specific survival of patients with small RCC (≤4 cm). Broken line represents patients with metastasis and solid line patients without metastasis.