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pT1 SUBSTAGING IN RENAL CELL CARCINOMA: VALIDATION OF THE 2002 TNM STAGING MODIFICATION OF MALIGNANT RENAL EPITHELIAL TUMORS
0022-5347/05/1735-1492/0 THE JOURNAL OF UROLOGY® Copyright © 2005 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 173, 1492–1495, May 2005 Printed in U.S.A.
DOI: 10.1097/01.ju.0000154693.68717.12
pT1 SUBSTAGING IN RENAL CELL CARCINOMA: VALIDATION OF THE 2002 TNM STAGING MODIFICATION OF MALIGNANT RENAL EPITHELIAL TUMORS M. E. SALAMA,* K. GURU, H. STRICKER, E. PETERSON, J. PEABODY, M. MENON, M. B. AMIN† AND M. DE PERALTA-VENTURINA‡ From the Departments of Pathology (MES, MBA, MDP-A), Urology (KG, HS, JP, MM) and Biostatistics and Research Epidemiology (EP), Henry Ford Hospital, Detroit, Michigan
ABSTRACT
Purpose: Tumor size has been used as one of the criteria to stratify renal cell carcinoma (RCC) into different pathological stages (pT). The recent 2002 UICC/TNM classification of malignant epithelial renal tumors is modified to substratify pT1 RCC into pT1a (less than 4.0 cm) and pT1b (greater than 4.0 but less than 7.0 cm). In this study we ascertained if this stage modification has prognostic relevance. Materials and Methods: A total of 259 consecutive radical nephrectomy specimens of organ confined RCC from 1970 to 1997 at 1 institution, including 153 of conventional RCC (CRCC), 71 of papillary RCC, 28 of chromophobe RCC, 1 of collecting duct carcinoma and 6 of RCC not otherwise specified, with a mean clinical followup of 7.5 years (median 6.4) were included in the study. Results: There were 115 pT1a (44.4%), 95 pT1b (36.7%) and 49 pT2 tumors (18.9%). Disease recurrences (DR) and disease specific death occurred in 2 (1.7%) and 0 cases (0%) of pT1a, 7 (7.3%) and 5 (5.3%) of pT1b, and 16 (32.6%) and 12 (24.5%) of pT2. DR for pT1b was higher compared with pT1a (all histological subtypes RR 3.68), although this difference was not statistically significant (p ⫽ 0.106). If only CRCCs were analyzed, DR in the pT1b group was statistically higher compared with pT1a (RR 8.54, p ⫽ 0.047). Disease specific survival in pT1a could not be evaluated because no deaths occurred in this subgroup. DR and disease specific survival were significantly different between pT1b and pT2 tumors for all histological subtypes (RR 5.51, p ⫽ 0.001 and 5.49, p ⫽ 0.001) and for the CRCC subtype (RR 5.50, p ⫽ 0.001 and 5.18, p ⫽ 0.005, respectively). Using size as a continuous variable the logarithmic change in tumor size was a significant predictor of DR (RR 8.82, p ⫽ 0.001). All statistical analyses were adjusted for age and sex. Conclusions: Substaging RCC into pT1a and pT1b yields prognostically important information, validating the 2002 TNM modification for malignant renal epithelial malignancies. The substratification of pT1 is particularly useful in tumors with CRCC histology. KEY WORDS: kidney; carcinoma; renal cell; neoplasm staging
Flocks and Kadesky first proposed a novel staging system for renal cell carcinoma (RCC) in 1958 that was based on the extent of the primary lesion.1 Because of additional pathological findings with prognostic value such as vascular involvement, Robson et al offered a modification of this staging scheme in 1969 and the latter has gained widespread acceptance in clinical practice.2, 3 In 1978 the UICC formulated a staging classification based on the TNM system.4 During the last 2 decades TNM staging for RCC has undergone multiple modifications by the American Joint Commission on Cancer and UICC. In the 1997 edition of UICC/American Joint Commission on Cancer staging the most significant change from the previous 1987 revision was an increase in the cutoff size between pT1 and pT2 tumors from 2.5 to 7.0 cm.5, 6 The recent 2002 TNM classification of malignant renal tumors is further modified to substratify pT1 RCC into pT1a (4.0 cm or less) and pT1b (greater than 4.0 to 7.0 cm or less).7
In this study we ascertained if this stage modification has prognostic and clinical relevance. MATERIALS AND METHODS
Between 1970 and 1997 we identified 259 patients who underwent radical nephrectomy for organ confined RCC who had available pathological slides and complete postoperative followup for at least 5 years. There were 153 conventional RCCs (CRCCs), 71 papillary RCCs, 28 chromophobe RCCs, 1 collecting duct carcinoma and 6 RCCs not otherwise specified. The 17 patients who underwent partial nephrectomy, those who had stages III and IV tumors, those with benign renal neoplasms such as oncocytoma and 27 with an unknown cause of death were excluded from study. Followup information, including the date of death, cause of death and date of recurrence, were obtained by retrospective review of hospital charts, tumor registry and death certificates. All nephrectomy specimens were reviewed by 2 pathologists blinded to the clinical outcome. Tumor size, measured as the maximum dimension of the primary tumor, was ascertained from the original histopathology reports. In 35 multifocal tumors the dimension of the largest tumor was used. There were 172 men and 87 women. Mean patient age at
Submitted for publication October 7, 2004. * Correspondence: Department of Pathology L235, Stanford University, 300 Pasteur Dr., Stanford, California 94305 (telephone: 650723-7211; FAX: 509-562-3941; e-mail: [email protected]). † Current address: Emory University Hospital, Atlanta, Georgia. ‡ Current address: William Beaumont Hospital, Royal Oak, Michigan. 1492
1493
pT1 SUBSTAGING IN RENAL CELL CANCER
nephrectomy was 60.3 years (range 22 to 91), and mean and median followup was 7.2 and 6.4 years, respectively. Primary tumor size was 0.5 to 22 cm (mean 5.3, median 4.5). Only 2 tumors were less than 1.0 cm and these 2 cases had multiple lesions. Disease specific survival (DSS) and disease recurrences (DR) were calculated. The impact of tumor size on DSS and freedom from progression was assessed by the log rank test. Kaplan-Meier survival curves were generated for survival and recurrence. To decrease the influence of large tumors logarithmic transformation of tumor size was used in the continuous model. Subsequent analyses used a Cox proportional hazards model approach with adjustments for age and sex. They were calculated for all histological subtypes and recalculated for CRCC only, the most common histological subtype of RCC. RESULTS
There were 115 (44.4%) tumors 4 cm or less (pT1a), 95 (36.7%) greater than 4 but 7 cm or less (pT1b) and 49 (18.9%) greater than 7 cm (pT2). The pT1a group had 2 recurrences (1.7%) and no deaths (0%), the pT1b group had 7 recurrences (7.3%) and 5 deaths (5.3%), and the pT2 group had 16 recurrences (32.6%) and 12 deaths (24.5%) (table 1). Of patients with multifocal tumors (35) only 1 (pT1b) died of the disease and another had recurrence. Average followup in patients who were alive with and without recurrence was 7.5 years. DR for pT1b was higher than for pT1a (all histological subtypes RR 3.68), although this difference was not statistically significant (p ⫽ 0.106). When tumors with clear cell histology were analyzed, DR in the pT1b group was statistically higher than in the pT1a group (RR 8.54, p ⫽ 0.047). DSS for pT1a vs pT1b was not evaluable statistically because no deaths occurred in the former group. DR and DSS were significantly different between pT1b and pT2 tumors for all histological subtypes (RR 5.51, p ⫽ 0.001 and 5.49, p ⫽ 0.001) and for the CRCC subtype only (RR 5.50, p ⫽ 0.001 and 5.18, p ⫽ 0.005, respectively, table 2). Figures 1 and 2 show the analysis of DSS and DR for all histological subtypes and for CRCC only. They were significantly different in the overall log rank test of differences. All analyses was adjusted for age and sex. We also examined the logarithmic transformation of size (continuous variable) as a predictor of DR. This was statistically significant (RR 8.62, p ⫽ 0.001). This was for a 1 log unit change in size (2.0 to 2.7 cm, 4.0 to 10.9, etc). We assumed an ordinal variable (obtained by size categorization) to estimate survival probabilities as a function of a continuous prognostic factor (tumor size). To evaluate the different cutoff points we looked at different definitions of pT1b, while leaving the high cutoff at 7.0 or 10.0 cm. We did not fit models until 3.0 to 7.0 cm due to absent disease recurrence in patients with tumors less than 2.0 cm. We concluded that the current cutoff points of 4.0 and 7.0 cm were reasonable.
TABLE 2. DR and death for all histological subtypes and for CRCC histology only pT1a vs pT1b Group
All histological subtypes: Recurrence Death CRCC: Recurrence Death
pT1b vs pT2
RR
p Value
RR
p Value
3.68 –
0.106 –
5.51 5.49
0.001 0.001
8.54 –
0.047 –
5.50 5.18
0.001 0.005
DISCUSSION
Previous studies have shown that tumor size is an important prognostic factor in patients with RCC as a continuous variable8 or based on an arbitrary cutoff point, which separates organ confined tumors into pT1 or pT2.9⫺16 The latter has been changed on several occasions, as reflected in the modifications of the TNM staging system for renal tumors. In 1987 the cutoff point was set at 2. 5 cm. However, in 1997 the cutoff point was increased to 7.0 cm. Javidan et al reported that, although 1997 staging was equivalent to that in 1987, there was better stratification of cases according to survival with the 1997 staging.17 More recent studies indicate that a better predictor of survival following radical nephrectomy was a cutoff point of 4.0,10 4.5,11 5.012⫺15 or 5.5 cm9, 16 rather than 7.0 cm. As we did, 1 group studied CRCC but, in contrast, they recommended 5 cm as the cutoff point for pT1a and pT1b.12 In this study we uniquely analyzed DR and DSS in CRCC and in all histological subtypes, and we addressed the prognostic difference between pT1b and pT2 tumors. This study was performed to evaluate the validity of the new 2002 TNM staging system modification, which substratifies pT1 into pT1a and pT1b with 4.0 cm as the cutoff point. Our results show that DR was statistically different between pT1a and pT1b in cases with CRCC histology (p ⫽ 0.047) but not for all histological subtypes combined. In addition, we reaffirmed the previous observation that there is significant prognostic separation between pT1b and pT2 tumors in disease recurrence and disease specific survival. A limitation that we faced in this analysis was the small sample size of recurrences, which limited the power of the analysis. Also, the absence of death from disease in the pT1a subgroup led to a technical problem in statistical analysis since the model fit tended to be less accurate. CONCLUSION
In this study we observed that substaging RCC into pT1a and pT1b yields prognostically important information, validating the 2002 TNM modifications. Cutoff points of 4.0 and 7.0 cm are reasonable and practical for pT1a/pT1b and pT1b/
TABLE 1. DR and DSS by tumor size for all histological subtypes and for CRCC histology only Tumor Stage (size)
No. Recurrence (%)
No. Death (%)
Total No. (%)
All subtypes: pT1a (4 cm or less) pT1b (greater than 4 but 7 cm or less) pT2 (greater than 7 cm)
2 (1.7) 7 (7.3) 16 (32.6)
0 5 (5.3)* 12 (24.5)
115 (44.4) 95 (36.7) 49 (18.9)
25 (9.6)
17 (6.6)
259 (100)
1 (1.4) 7 (10.4) 12 (54.5)*
0 5 (8.1) 8 (36.4)
69 (45.0) 62 (40.5) 22 (14.4)
20 (13.1)
13 (8.5)
153 (100)
Totals CRCC: pT1a (4 cm or less) pT1b (greater than 4 but 7 cm or less) pT2 (greater than 7 cm) Totals * Multifocal tumor in 1 patient.
1494
pT1 SUBSTAGING IN RENAL CELL CANCER
FIG. 1. Kaplan-Meier survival curves for DR
FIG. 2. Kaplan-Meier survival curves for DSS
pT2, respectively. The substratification of pT1 is particularly useful in tumors with CRCC histology. Since the greatest prognostic separation occurs at 7.0 cm, further modifications of the pT1/pT2 cutoff do not seem warranted. REFERENCES
1. Flocks, R. H. and Kadesky, M. C.: Malignant neoplasm of the kidney: an analysis of 353 patients followed 5 years or more. J Urol, 79: 196, 1958 2. Robson, C. J.: Radical nephrectomy for renal cell carcinoma. J Urol, 89: 37, 1963 3. Robson, C. J., Churchill, B. M. and Anderson, W.: The results of radical nephrectomy for renal cell carcinoma. J Urol, 101: 297, 1969 4. Harmer, M.: TNM Classification of Malignant Tumors, 3rd ed. Geneva: International Union Against Cancer, pp. 109 –112, 1978 5. Hermanek, P. and Sobin, L. H.: TNM Classification of Malignant Tumours, 4th ed. Tokyo: Springer-Verlag, pp. 136 –138, 1987 6. Sobin, L. H. and Wittekind, C.: TNM Classification of Malignant
7. 8.
9.
10.
11.
Tumours, 5th ed. New York: John Wiley & Sons, pp. 180 –182, 1997 Sobin, L. H. and Wittekind, C.: TNM Classification of Malignant Tumours, 6th ed. New York: Wiley-Liss Publications, pp. 193– 195, 2002 Delahunt, B., Kittelson, J. M., McCredie, M. R., Reeve, A. E., Stewart, J. H. and Bilous, A. M.: Prognostic importance of tumor size for localized conventional (clear cell) renal cell carcinoma: assessment of TNM T1 and T2 tumor categories and comparison with other prognostic parameters. Cancer, 94: 658, 2002 Kinouchi, T., Saiki, S., Meguro, N., Maeda, O., Kuroda, M., Usami, M. et al: Impact of tumor size on the clinical outcomes of patients with Robson State I renal cell carcinoma. Cancer, 85: 689, 1999 Igarashi, T., Tobe, T., Nakatsu, H.-O., Suzuki, N., Murakami, S., Hamano, M. et al: The impact of a 4 cm. cutoff point for stratification of T1N0M0 renal cell carcinoma after radical nephrectomy. J Urol, 165: 1103, 2001 Zisman, A., Pantuck, A. J., Chao, D., Dorey, F., Said, J. W.,
pT1 SUBSTAGING IN RENAL CELL CANCER Gitlitz, B. J. et al: Reevaluation of the 1997 TNM classification for renal cell carcinoma: T1 and T2 cutoff point at 4.5 rather than 7 cm. better correlates with clinical outcome J Urol, 166: 54, 2001 12. Lau, W. K., Cheville, J. C., Blute, M. L., Weaver, A. L. and Zincke, H.: Prognostic features of pathologic stage T1 renal cell carcinoma after radical nephrectomy. Urology, 59: 532, 2002 13. Zucchi, A., Mearini, L., Mearini, E. and Constantini, E.: Stage pT1 renal cell carcinoma: review of the prognostic significance of size. Urol Int, 70: 47, 2003 14. Elmore, J. M., Kadesky, K. T., Koeneman, K. S. and Sagalowsky, A. I.: Reassessment of the 1997 TNM classification system for
1495
renal cell carcinoma. Cancer, 98: 2329, 2003 15. Cheville, J. C., Blute, M. L., Zincke, H., Lohse, C. M. and Weaver, A. L.: Stage pT1 conventional (clear cell) renal cell carcinoma: pathological features associated with cancer specific survival. J Urol, 166: 453, 2001 16. Ficarra, V., Prayer-Galetti, T., Novara, G., Brati, E., Zanolla, L., Dal Bianco et al: Tumor size breakpoint for prognostic stratification of localized renal cell carcinoma. Urology, 63: 235, 2004 17. Javidan, J., Stricker, H. J., Tamboli, P., Amin, M. B., Peabody, J. O., Deshpande, A. et al: Prognostic significance of the 1997 TNM classification of renal cell carcinoma. J Urol, 162: 1277, 1999
Vol. 173, 1492–1495, May 2005 Printed in U.S.A.
DOI: 10.1097/01.ju.0000154693.68717.12
pT1 SUBSTAGING IN RENAL CELL CARCINOMA: VALIDATION OF THE 2002 TNM STAGING MODIFICATION OF MALIGNANT RENAL EPITHELIAL TUMORS M. E. SALAMA,* K. GURU, H. STRICKER, E. PETERSON, J. PEABODY, M. MENON, M. B. AMIN† AND M. DE PERALTA-VENTURINA‡ From the Departments of Pathology (MES, MBA, MDP-A), Urology (KG, HS, JP, MM) and Biostatistics and Research Epidemiology (EP), Henry Ford Hospital, Detroit, Michigan
ABSTRACT
Purpose: Tumor size has been used as one of the criteria to stratify renal cell carcinoma (RCC) into different pathological stages (pT). The recent 2002 UICC/TNM classification of malignant epithelial renal tumors is modified to substratify pT1 RCC into pT1a (less than 4.0 cm) and pT1b (greater than 4.0 but less than 7.0 cm). In this study we ascertained if this stage modification has prognostic relevance. Materials and Methods: A total of 259 consecutive radical nephrectomy specimens of organ confined RCC from 1970 to 1997 at 1 institution, including 153 of conventional RCC (CRCC), 71 of papillary RCC, 28 of chromophobe RCC, 1 of collecting duct carcinoma and 6 of RCC not otherwise specified, with a mean clinical followup of 7.5 years (median 6.4) were included in the study. Results: There were 115 pT1a (44.4%), 95 pT1b (36.7%) and 49 pT2 tumors (18.9%). Disease recurrences (DR) and disease specific death occurred in 2 (1.7%) and 0 cases (0%) of pT1a, 7 (7.3%) and 5 (5.3%) of pT1b, and 16 (32.6%) and 12 (24.5%) of pT2. DR for pT1b was higher compared with pT1a (all histological subtypes RR 3.68), although this difference was not statistically significant (p ⫽ 0.106). If only CRCCs were analyzed, DR in the pT1b group was statistically higher compared with pT1a (RR 8.54, p ⫽ 0.047). Disease specific survival in pT1a could not be evaluated because no deaths occurred in this subgroup. DR and disease specific survival were significantly different between pT1b and pT2 tumors for all histological subtypes (RR 5.51, p ⫽ 0.001 and 5.49, p ⫽ 0.001) and for the CRCC subtype (RR 5.50, p ⫽ 0.001 and 5.18, p ⫽ 0.005, respectively). Using size as a continuous variable the logarithmic change in tumor size was a significant predictor of DR (RR 8.82, p ⫽ 0.001). All statistical analyses were adjusted for age and sex. Conclusions: Substaging RCC into pT1a and pT1b yields prognostically important information, validating the 2002 TNM modification for malignant renal epithelial malignancies. The substratification of pT1 is particularly useful in tumors with CRCC histology. KEY WORDS: kidney; carcinoma; renal cell; neoplasm staging
Flocks and Kadesky first proposed a novel staging system for renal cell carcinoma (RCC) in 1958 that was based on the extent of the primary lesion.1 Because of additional pathological findings with prognostic value such as vascular involvement, Robson et al offered a modification of this staging scheme in 1969 and the latter has gained widespread acceptance in clinical practice.2, 3 In 1978 the UICC formulated a staging classification based on the TNM system.4 During the last 2 decades TNM staging for RCC has undergone multiple modifications by the American Joint Commission on Cancer and UICC. In the 1997 edition of UICC/American Joint Commission on Cancer staging the most significant change from the previous 1987 revision was an increase in the cutoff size between pT1 and pT2 tumors from 2.5 to 7.0 cm.5, 6 The recent 2002 TNM classification of malignant renal tumors is further modified to substratify pT1 RCC into pT1a (4.0 cm or less) and pT1b (greater than 4.0 to 7.0 cm or less).7
In this study we ascertained if this stage modification has prognostic and clinical relevance. MATERIALS AND METHODS
Between 1970 and 1997 we identified 259 patients who underwent radical nephrectomy for organ confined RCC who had available pathological slides and complete postoperative followup for at least 5 years. There were 153 conventional RCCs (CRCCs), 71 papillary RCCs, 28 chromophobe RCCs, 1 collecting duct carcinoma and 6 RCCs not otherwise specified. The 17 patients who underwent partial nephrectomy, those who had stages III and IV tumors, those with benign renal neoplasms such as oncocytoma and 27 with an unknown cause of death were excluded from study. Followup information, including the date of death, cause of death and date of recurrence, were obtained by retrospective review of hospital charts, tumor registry and death certificates. All nephrectomy specimens were reviewed by 2 pathologists blinded to the clinical outcome. Tumor size, measured as the maximum dimension of the primary tumor, was ascertained from the original histopathology reports. In 35 multifocal tumors the dimension of the largest tumor was used. There were 172 men and 87 women. Mean patient age at
Submitted for publication October 7, 2004. * Correspondence: Department of Pathology L235, Stanford University, 300 Pasteur Dr., Stanford, California 94305 (telephone: 650723-7211; FAX: 509-562-3941; e-mail: [email protected]). † Current address: Emory University Hospital, Atlanta, Georgia. ‡ Current address: William Beaumont Hospital, Royal Oak, Michigan. 1492
1493
pT1 SUBSTAGING IN RENAL CELL CANCER
nephrectomy was 60.3 years (range 22 to 91), and mean and median followup was 7.2 and 6.4 years, respectively. Primary tumor size was 0.5 to 22 cm (mean 5.3, median 4.5). Only 2 tumors were less than 1.0 cm and these 2 cases had multiple lesions. Disease specific survival (DSS) and disease recurrences (DR) were calculated. The impact of tumor size on DSS and freedom from progression was assessed by the log rank test. Kaplan-Meier survival curves were generated for survival and recurrence. To decrease the influence of large tumors logarithmic transformation of tumor size was used in the continuous model. Subsequent analyses used a Cox proportional hazards model approach with adjustments for age and sex. They were calculated for all histological subtypes and recalculated for CRCC only, the most common histological subtype of RCC. RESULTS
There were 115 (44.4%) tumors 4 cm or less (pT1a), 95 (36.7%) greater than 4 but 7 cm or less (pT1b) and 49 (18.9%) greater than 7 cm (pT2). The pT1a group had 2 recurrences (1.7%) and no deaths (0%), the pT1b group had 7 recurrences (7.3%) and 5 deaths (5.3%), and the pT2 group had 16 recurrences (32.6%) and 12 deaths (24.5%) (table 1). Of patients with multifocal tumors (35) only 1 (pT1b) died of the disease and another had recurrence. Average followup in patients who were alive with and without recurrence was 7.5 years. DR for pT1b was higher than for pT1a (all histological subtypes RR 3.68), although this difference was not statistically significant (p ⫽ 0.106). When tumors with clear cell histology were analyzed, DR in the pT1b group was statistically higher than in the pT1a group (RR 8.54, p ⫽ 0.047). DSS for pT1a vs pT1b was not evaluable statistically because no deaths occurred in the former group. DR and DSS were significantly different between pT1b and pT2 tumors for all histological subtypes (RR 5.51, p ⫽ 0.001 and 5.49, p ⫽ 0.001) and for the CRCC subtype only (RR 5.50, p ⫽ 0.001 and 5.18, p ⫽ 0.005, respectively, table 2). Figures 1 and 2 show the analysis of DSS and DR for all histological subtypes and for CRCC only. They were significantly different in the overall log rank test of differences. All analyses was adjusted for age and sex. We also examined the logarithmic transformation of size (continuous variable) as a predictor of DR. This was statistically significant (RR 8.62, p ⫽ 0.001). This was for a 1 log unit change in size (2.0 to 2.7 cm, 4.0 to 10.9, etc). We assumed an ordinal variable (obtained by size categorization) to estimate survival probabilities as a function of a continuous prognostic factor (tumor size). To evaluate the different cutoff points we looked at different definitions of pT1b, while leaving the high cutoff at 7.0 or 10.0 cm. We did not fit models until 3.0 to 7.0 cm due to absent disease recurrence in patients with tumors less than 2.0 cm. We concluded that the current cutoff points of 4.0 and 7.0 cm were reasonable.
TABLE 2. DR and death for all histological subtypes and for CRCC histology only pT1a vs pT1b Group
All histological subtypes: Recurrence Death CRCC: Recurrence Death
pT1b vs pT2
RR
p Value
RR
p Value
3.68 –
0.106 –
5.51 5.49
0.001 0.001
8.54 –
0.047 –
5.50 5.18
0.001 0.005
DISCUSSION
Previous studies have shown that tumor size is an important prognostic factor in patients with RCC as a continuous variable8 or based on an arbitrary cutoff point, which separates organ confined tumors into pT1 or pT2.9⫺16 The latter has been changed on several occasions, as reflected in the modifications of the TNM staging system for renal tumors. In 1987 the cutoff point was set at 2. 5 cm. However, in 1997 the cutoff point was increased to 7.0 cm. Javidan et al reported that, although 1997 staging was equivalent to that in 1987, there was better stratification of cases according to survival with the 1997 staging.17 More recent studies indicate that a better predictor of survival following radical nephrectomy was a cutoff point of 4.0,10 4.5,11 5.012⫺15 or 5.5 cm9, 16 rather than 7.0 cm. As we did, 1 group studied CRCC but, in contrast, they recommended 5 cm as the cutoff point for pT1a and pT1b.12 In this study we uniquely analyzed DR and DSS in CRCC and in all histological subtypes, and we addressed the prognostic difference between pT1b and pT2 tumors. This study was performed to evaluate the validity of the new 2002 TNM staging system modification, which substratifies pT1 into pT1a and pT1b with 4.0 cm as the cutoff point. Our results show that DR was statistically different between pT1a and pT1b in cases with CRCC histology (p ⫽ 0.047) but not for all histological subtypes combined. In addition, we reaffirmed the previous observation that there is significant prognostic separation between pT1b and pT2 tumors in disease recurrence and disease specific survival. A limitation that we faced in this analysis was the small sample size of recurrences, which limited the power of the analysis. Also, the absence of death from disease in the pT1a subgroup led to a technical problem in statistical analysis since the model fit tended to be less accurate. CONCLUSION
In this study we observed that substaging RCC into pT1a and pT1b yields prognostically important information, validating the 2002 TNM modifications. Cutoff points of 4.0 and 7.0 cm are reasonable and practical for pT1a/pT1b and pT1b/
TABLE 1. DR and DSS by tumor size for all histological subtypes and for CRCC histology only Tumor Stage (size)
No. Recurrence (%)
No. Death (%)
Total No. (%)
All subtypes: pT1a (4 cm or less) pT1b (greater than 4 but 7 cm or less) pT2 (greater than 7 cm)
2 (1.7) 7 (7.3) 16 (32.6)
0 5 (5.3)* 12 (24.5)
115 (44.4) 95 (36.7) 49 (18.9)
25 (9.6)
17 (6.6)
259 (100)
1 (1.4) 7 (10.4) 12 (54.5)*
0 5 (8.1) 8 (36.4)
69 (45.0) 62 (40.5) 22 (14.4)
20 (13.1)
13 (8.5)
153 (100)
Totals CRCC: pT1a (4 cm or less) pT1b (greater than 4 but 7 cm or less) pT2 (greater than 7 cm) Totals * Multifocal tumor in 1 patient.
1494
pT1 SUBSTAGING IN RENAL CELL CANCER
FIG. 1. Kaplan-Meier survival curves for DR
FIG. 2. Kaplan-Meier survival curves for DSS
pT2, respectively. The substratification of pT1 is particularly useful in tumors with CRCC histology. Since the greatest prognostic separation occurs at 7.0 cm, further modifications of the pT1/pT2 cutoff do not seem warranted. REFERENCES
1. Flocks, R. H. and Kadesky, M. C.: Malignant neoplasm of the kidney: an analysis of 353 patients followed 5 years or more. J Urol, 79: 196, 1958 2. Robson, C. J.: Radical nephrectomy for renal cell carcinoma. J Urol, 89: 37, 1963 3. Robson, C. J., Churchill, B. M. and Anderson, W.: The results of radical nephrectomy for renal cell carcinoma. J Urol, 101: 297, 1969 4. Harmer, M.: TNM Classification of Malignant Tumors, 3rd ed. Geneva: International Union Against Cancer, pp. 109 –112, 1978 5. Hermanek, P. and Sobin, L. H.: TNM Classification of Malignant Tumours, 4th ed. Tokyo: Springer-Verlag, pp. 136 –138, 1987 6. Sobin, L. H. and Wittekind, C.: TNM Classification of Malignant
7. 8.
9.
10.
11.
Tumours, 5th ed. New York: John Wiley & Sons, pp. 180 –182, 1997 Sobin, L. H. and Wittekind, C.: TNM Classification of Malignant Tumours, 6th ed. New York: Wiley-Liss Publications, pp. 193– 195, 2002 Delahunt, B., Kittelson, J. M., McCredie, M. R., Reeve, A. E., Stewart, J. H. and Bilous, A. M.: Prognostic importance of tumor size for localized conventional (clear cell) renal cell carcinoma: assessment of TNM T1 and T2 tumor categories and comparison with other prognostic parameters. Cancer, 94: 658, 2002 Kinouchi, T., Saiki, S., Meguro, N., Maeda, O., Kuroda, M., Usami, M. et al: Impact of tumor size on the clinical outcomes of patients with Robson State I renal cell carcinoma. Cancer, 85: 689, 1999 Igarashi, T., Tobe, T., Nakatsu, H.-O., Suzuki, N., Murakami, S., Hamano, M. et al: The impact of a 4 cm. cutoff point for stratification of T1N0M0 renal cell carcinoma after radical nephrectomy. J Urol, 165: 1103, 2001 Zisman, A., Pantuck, A. J., Chao, D., Dorey, F., Said, J. W.,
pT1 SUBSTAGING IN RENAL CELL CANCER Gitlitz, B. J. et al: Reevaluation of the 1997 TNM classification for renal cell carcinoma: T1 and T2 cutoff point at 4.5 rather than 7 cm. better correlates with clinical outcome J Urol, 166: 54, 2001 12. Lau, W. K., Cheville, J. C., Blute, M. L., Weaver, A. L. and Zincke, H.: Prognostic features of pathologic stage T1 renal cell carcinoma after radical nephrectomy. Urology, 59: 532, 2002 13. Zucchi, A., Mearini, L., Mearini, E. and Constantini, E.: Stage pT1 renal cell carcinoma: review of the prognostic significance of size. Urol Int, 70: 47, 2003 14. Elmore, J. M., Kadesky, K. T., Koeneman, K. S. and Sagalowsky, A. I.: Reassessment of the 1997 TNM classification system for
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