Tumor size is an important prognostic indicator for RCC. Outcome of nephrectomy has been studied according to pathological tumor size. Pre-operatively, we must rely upon CT estimates of pathological tumor size to guide counseling regarding prognosis and choice of treatment modality. Furthermore, ablative techniques for renal tumors do not provide specimens for pathological assessment of tumor size. When comparing emerging ablative techniques to the benchmark of nephrectomy, we are comparing data based on pathological tumor size to data based on CT size. Therefore, it is important to understand the relationship between radiological tumor size and pathological tumor size, and to understand how any difference between the two measurements affects the accuracy of clinical staging.
Our study of a contemporary Australian cohort found that overall CT overestimated pathological tumor size by a statistically significant but small amount (3.1 mm). This observation is consistent with the findings of previous studies. The findings of recent papers comparing mean radiological and mean pathological renal tumors sizes are summarized in Table
. Kurta et al[28
] reported on the largest series (N
= 521), and found that mean radiological tumor size was larger than mean pathological tumor size by 1 mm. Similarly, CT was found to overestimate pathological tumor size overall by 6.3 mm in a study by Herr[35
], and by 10.0 mm in a paper by Irani et al[33
]. Schlomer et al[31
] found no statistically significant difference overall, but found that CT overestimated pathological size for pT1a tumors by 3.9 mm and for lesions 40 to 50 mm by 8.7 mm. Similarly, Lee et al[24
] found a statistically significant overestimation of pathological tumor size by CT for tumors in the 40 to 50 mm range only, by an average of 2 mm. Choi et al[25
] found that CT tumor size was on average larger than pathological size for smaller tumors only (<6 cm or T1). In several other series, mean radiological tumor size was greater than mean pathological size, but the difference did not reach statistical significance[27
]. Only one study reported an underestimation of pathological tumor size by CT overall, and this achieved statistical significance for T1a tumors only[26
Summary of previous studies comparing mean radiological and mean pathological renal tumor sizes.
Analysis by histological subtype in our series showed a statistically significant difference for conventional RCC only, with CT overestimating pathological size by an average of 3.8 mm. The small number of papillary (N
= 18) and chromophobe (N
= 11) tumors included in our study meant we were unlikely to detect a statistically significant difference. Several studies have shown that CT size is greater than pathological size on average for conventional RCC, and smaller than pathological size on average for papillary RCC[24
]. Kurta et al[28
] found that CT overestimated pathological tumor size by 2.3 mm for conventional RCC and underestimated pathological tumor size by 5.4 mm for papillary RCC. Similarly, Lee et al[24
] found that CT size was 1.4 mm greater than pathological size on average for conventional RCC, and 5.3 mm smaller for papillary RCC. In contrast, Herr[34
] found that pathological size was overestimated on CT for all histological subtypes, and that the overestimation was significantly greater for conventional RCC compared to other subtypes (9.7 mm versus 3.9 mm). Similarly, Choi et al[25
] demonstrated that mean radiological tumor size was larger than mean pathological tumor size for all histological subtypes, but there was no significant difference between groups.
The discrepancy between clinical and pathological tumor size has been attributed to decreased tumor vascularity after excision, leading to a diminished size post-operatively[34
]. This effect is probably more pronounced for clear cell carcinomas because they typically have a richer vascular network than other histological subtypes. Yaycioglu et al[32
] postulated that certain radiological and pathological features might influence the accuracy of tumor size measurement by CT. These features included: concomitant pyelonephritis, presence of hemorrhage or hematoma, cystic tumor or adjacent cysts, dilatation of adjacent renal calyces and invasion of the collecting system. The same study found that tumor invasion of perinephric tissues impacted upon the accuracy of CT. For these tumors, CT more frequently underestimated pathological size when compared to tumors confined to the kidney. Ates et al[26
] demonstrated less accurate CT measurement of tumor size for locally invasive tumors. It may be more difficult to delineate the radiographic margin of invasive tumors on CT, leading to disagreement between radiological and pathological tumor sizes. Ates et al[26
] also found more accurate measurement of tumors size on CT for exophytic lesions. Herr[35
] found that CT more closely approximated pathological tumor size for upper pole tumors, but other studies have failed to confirm this finding[24
]. Additionally, in our study the radiological and pathological tumor sizes were not necessarily measured in the same geometric plane and this could contribute to the discrepancy between the two measurements. The largest tumor diameter on CT was measured in the axial plane, and this did not always correspond to the plane in which the largest diameter was measured at pathological exam. Formalin fixation is known to cause tumor shrinkage[38
], but in our series the pathological specimens were examined prior to fixation.
Inaccurate CT estimation of pathological tumor size led to discordance between clinical and pathological stage in over one quarter of tumors limited to the kidney in our study (pT1, pT2). Of these, 21 (17%) patients were down-staged and 14 (11.5%) up-staged post-operatively. There is limited published data on the impact that disagreement between radiological and pathological tumor sizes may have on staging discrepancies. Kanofsky et al[30
] reported on a series of 198 renal cell carcinomas and identified 21 patients for whom disagreement between CT and pathological tumor size led to discrepancy between clinical and pathological tumor stage. Of these, 15 patients were down-staged and 6 up-staged post-operatively. Ates et al[26
] found that differences between radiological and pathological measurements led to staging discrepancies in 19 of 86 patients, with 6 patients being down-staged and 13 patients being up-staged post-operatively. Kurta et al[28
] and Lee et al[24
] only reported cases of post-operative down-staging. Kurta et al demonstrated that among 258 patients with CT tumor size greater than 4 cm, 30 (11.6%) had a pathological size of less than 4 cm. Among 92 patients with CT tumor size greater than 7 cm, 7 (7.6%) had a pathological size of less than 7 cm. Lee et al demonstrated similar results. Of the 141 patients with CT tumor size between 4 cm and 7 cm, 17 (12.1%) had a pathological size less than 4 cm. Of the 87 patients with CT tumor size greater than 7 cm, 8 (9.2%) had a pathological size of less than 7 cm.
For these patients, pre-operative counseling regarding prognosis and management would have been based on a clinical tumor stage that was ultimately down-staged or up-staged based on pathological tumor size. Thus, although the magnitude of the mean difference between radiological and pathological tumor sizes is only 3.1 mm, there are cases where the discrepancy may impact upon clinical management.
Authors disagree about the clinical implications of the small but statistically significant difference between CT and pathological tumor size. Some studies conclude that CT adequately approximates pathological tumor size[24
], and that any discrepancy between the two measurements has minimal impact on patient management[28
]. Other authors point out that overestimation of pathological size on CT could affect selection of patients for elective PN[29
]. PN is the standard of care for T1a tumors (≤4 cm) [17
]. Mistry et al[29
] report that 5 (5%) of their patients who were not offered elective PN based on a CT tumor size > 40 mm, had a pathological size ≤4 cm. Likewise, 3 patients out of 100 included in the study by Irani et al[33
] were ineligible for elective PN based on CT size > 40 mm, but had a pathological size ≤4 cm. However, with the growing impetus to use PN for all amenable T1 tumors[15
], tumor size is becoming less important for determining patient eligibility for PN. Several authors argue that the decision to perform elective PN should be based on technical feasibility and patient preference rather than a rigid tumor size cut-off[12
The discrepancy between radiological and pathological tumor size could have implications for the use of ablative techniques and active surveillance for RCC. These approaches produce no specimen for pathological assessment, and so we must rely upon CT estimates of tumor size to guide management. Decision-making under these circumstances is aided by the small number of studies that report tumor prognosis according to radiological tumor size. Kanao et al[40
] have recently developed a preoperative prognostic nomogram based on clinical staging to predict survival after nephrectomy. Raj et al[41
] have also developed a preoperative nomogram to predict the development of metastases after nephrectomy. Such prognostic data based on clinical information can be used as a benchmark against which the oncological outcome of ablative techniques can be compared.
Our finding of a positive correlation between Fuhrman grade and tumor size supports previous observations. Thompson et al[42
] (N =
1523) and Frank et al[43
] (N =
2559) both demonstrated that larger tumors were more likely to harbor high-grade disease, with each 1 cm increase in tumor size carrying a 25 - 32% increased risk of high-grade disease (Fuhrman 3 or 4). Analysis of tumors grouped according to various tumor size breakpoints (3 cm[44
], 4 cm[45
], 5 cm[46
]) has also shown a higher prevalence of high-grade disease in the larger size groups. In contrast, Klatte et al classified tumors by an 11 cm breakpoint and found that Fuhrman grade was similar in the two groups[47
]. Our finding that Fuhrman grade correlated with tumor stage is also consistent with findings from other studies[48
]. The relationship between tumor size and Fuhrman grade has implications for patient counseling and management, particularly if electing active surveillance.
Our study has several shortcomings. It is a retrospective single institution analysis. The small numbers of papillary and chromophobe histological subtypes, and the small number of patients treated with partial nephrectomy were inadequately powered to detect a difference. Likewise, when categorized into 1 cm size intervals, several groups had insufficient numbers to detect a difference. There was no record of when the pre-operative CT was performed, and so we could not standardize the interval between imaging and surgery. Furthermore, there was no uniform protocol for measurement of CT tumor size and pathological tumor size. There was no centralized review of measurements by a single radiologist or pathologist.
A follow-up prospective multi-centre study with larger numbers and a uniform protocol for tumor measurement should be performed to further elucidate the relationship between CT and pathological tumor size. There is also a need for studies examining the correlation between clinical and pathological staging for RCC. Studies that report prognosis according to radiological rather than pathological tumor size would guide us in making treatment decisions based on clinical tumor size. The development and validation of pre-operative prognostic nomograms would also aid decision-making.