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Surgical evaluation of lymph node metastases in Wilms' tumor
Surgical
Evaluation By H. Biemann
of Lymph Node Metastases
Othersen,
Jr, Alfred DeLorimer,
Norman Charleston,
South Carolina; San Francisco,
Breslow,
Panayotis
Kelalis,
and Giulio J. D’Angio
California;
Seattle,- Washington;
Ellen Hrabovsky,
in Wilms’ Tumor
Morgantown,
and Philadelphia,
West Virginia; Rochester,
Minnesota;
Pennsylvania
0 Because lymph node (LN) involvement continues to be an adverse prognostic factor in the later National Wilms’ Tumor Study (NWTS) trials, the NWTS-3 Surgical Committee undertook a project to determine the accuracy of the present method of sampling. The committee concludes that: (1) there is a relatively low potential error rate ItlO%) that would comprise adequate care when a policy of LN sampling is followed: (2) this does not encourage routine radical LN dissections in Wilms’ tumor patients because of the well-known morbidities associated with that procedure: and (3) LN sampling in all Wilms’ tumor patients should be performed with a high index of suspicion present in the mind of the operating surgeon. e 199y1by W.B. Saunders Company.
estimate of the operating surgeon, when he considered the LNs to be negative, and the pathologist’s findings.’
INDEX WORDS: Wilms’ tumor, lymph node metastases.
Data from 126 unselected cases were gathered and tabulated (Table 1). The false-negative and falsepositive rates were 10 of 32 (31.3%), and 17 of 94 (18.1%) respectively. The predictive value of a surgical “positive” estimate was 22 of 39 (56.4%).
T
HE FIRST NATIONAL Wilms’ Tumor Study (NWTS-1) confirmed the observations by Jereb et al’ that lymph node (LN) metastases carried a greater risk of recurrence. A review of NWTS-2 and NWTS-3 patients with stage I to III tumors showed that of the 214 patients in whom LN were not examined or noted, there was a 12.6% relapse rate and 8.9% died. The rest&s were similar when the LN were pathologically negative in 1,067 patients: 13.8% relapsed and 8.6% died.2d With positive LNs confined to the renal hilum, the relapse rate increased to 22.4%, with death occurring in 13.8%. When the nodal involvement extended to the aortic or other LNs, relapses reached a high of 46.2%, with death in 39.6%. Therefore, all patients with positive LNs are now.placed in stage III.4 An earlier report from the NWTS-1 Surgical Committee showed a good concordance (96%) between the From the Medical Urnkersity Hospital, Charleston, SC; University of California. San Francisco, CA; West Virginia University, Morgantown, WV; Mayo Clinic, Rochester, MN; University of Wahington, Seattle, WA; and The Children’s Hospital of Philadelphia, Philadelphia, PA. For The National Wilms’ Tumor Stu& (NWTS) Group. Supported in part by USPHS Grant No. CA-42326. Principal investigators at participating institutions also receive independent supportfrom theNational Cancer Institute. Date accepted: February 17.1989. Address reprints requests to Giulio J. D;Qngio. MD. Department of Radiation Oncology, Hospital of the University of Pennsylvania. Philadelphia. PA I91 04. 8 1990 by W.B. Saunders Company. 0022-3468/90/2503-0014$03.00/0
330
MATERIALS
AND
METHODS
The cooperation of 31 pediatric surgeons and urologists was
enlisted. All patients coming under their care were to have complete LN sampling, and statements entered on a form as to whether they considered identifiable LNs to be positive or negative. The operative procedures were not radical LN dissections; rather, they were excisions of identifiable LNs, encountered in the periaortic regions, that did not accompany the excision specimen as part of a standard nephrectomy. RESULTS
DISCUSSION
The prognostic importance of positive LNs in Wilms’ tumor patients is well established, and has led some authorities to advocate radical node dissections in managing such children.6 Leape et al,’ in their review of patients entered in the first NWTS, could reach no conclusion regarding the possible value of formal LN dissections but stressed the need for adequate LN sampling. The more systematic investigation reported here confirms that need. An important consideration is how often the surgeon would have been wrong in not sampling a node he considered negative, That figure would seem to be about 11% in this study (10187) (Table 1). That is, 11% of patients would have been down-staged inaccurately to stage II, barring other criteria for stage III. By contrast, 44% (17/39) would have been erroneously up-staged on the surgeon’s estimate alone, and overtreated as a result. Perhaps an even more cogent consideration is the following: 126 patients underwent LN sampling. The surgeons made erroneous estimates both ways, but the LNs that were incorrectly assessed as positive were corrected by the pathologists. Since suspicious LN will always be biopsied, such patients will almost invariably be correctly staged. However, as many as 8% (10/126) might have been falsely down-staged if the surgeon had acted on his opinion and not sampled the node(s).
Journalof
Pediatric Surgery, Vol 25, No 3 blarch),
1990: pp 330-331
331
LYMPH NODES IN WILMS’ TUMOR
Table 1. Evaluation of Lymph Nodes by Surgeon and Pathologist Surgeon’s
Path&gist’s Positive
Evaluaion
Evaluation Total
Neeative
Positive
22
10
32
Negative
17
77
94
Total
39
a7
126
(This is a maximum figure, because some will have positive hilar nodes that come with the specimen. These will be identified by the pathologist, and stage. III will be assigned correctly.) The children would therefore not have received the more intensive treatment currently being advocated for stage III children;
ie, the addition of tumor bed irradiation (RT) and Adriamycin (ADR) to actinomycin D and vincristine. Neither RT nor ADR is used in stage II favorable histology (FH) tumor patients. The 4-year relapse-free and survival rates for stage III/FH patients treated with 1000 cGy RT and three drugs are 82% and 91%, respectively,very similar to the 87% and 91% recorded for corresponding end-points in stage II/FH children.7 ACKNOWLEDGMENT The authors gratefully acknowledge the contributions of 31 pediatric surgeons and pediatric urologists who contributed patients to this study. Their dedicated descriptions and lymph node biopsies were essential to this investigation.
REFERENCES 1. Jereb B, Tournade MF, Lemerle J: Lymph node invasion and prognosis in nephroblastoma. Cancer 45:1632-1636, 1980 2. Breslow N, Churchill G, Beckwith JB, et al: Prognosis for Wilms’ tumor patients with non-metastatic disease at diagnosisResults of the second National Wilms’ Tumor Study. J Clin Oncol 3:521-531, 1985 3. Unpublished Study. 4. Farewell
observations
VT, D’Angio
of the
GJ, Breslow
National
Wilms’
Tumor
N, et al: Retrospective
validation of a new staging system for Wilms’ tumor. Cancer Clin Trials4:167-171, 1981 5. Leape L, Breslow N, Bishop HC: The surgical treatment of Wilms’ tumor: Results of the National Wilms’ Tumor Study. Ann Surg 187:351-356.1978 6. Martin LW, Reyes PM, Jr: An evaluation- of 10 years’ experience with retroperitoneal lymph node dissection for Wilms’ tumor. J Pediatr Surg 4:683-xxx, 1969 7. D’Angio GJ, Breslow N, Beckwith JB, et al: The treatment of Wilms’ tumor: Results of the Third National Wilms’ Tumor Study. Cancer 64:349-360, 1989
Evaluation By H. Biemann
of Lymph Node Metastases
Othersen,
Jr, Alfred DeLorimer,
Norman Charleston,
South Carolina; San Francisco,
Breslow,
Panayotis
Kelalis,
and Giulio J. D’Angio
California;
Seattle,- Washington;
Ellen Hrabovsky,
in Wilms’ Tumor
Morgantown,
and Philadelphia,
West Virginia; Rochester,
Minnesota;
Pennsylvania
0 Because lymph node (LN) involvement continues to be an adverse prognostic factor in the later National Wilms’ Tumor Study (NWTS) trials, the NWTS-3 Surgical Committee undertook a project to determine the accuracy of the present method of sampling. The committee concludes that: (1) there is a relatively low potential error rate ItlO%) that would comprise adequate care when a policy of LN sampling is followed: (2) this does not encourage routine radical LN dissections in Wilms’ tumor patients because of the well-known morbidities associated with that procedure: and (3) LN sampling in all Wilms’ tumor patients should be performed with a high index of suspicion present in the mind of the operating surgeon. e 199y1by W.B. Saunders Company.
estimate of the operating surgeon, when he considered the LNs to be negative, and the pathologist’s findings.’
INDEX WORDS: Wilms’ tumor, lymph node metastases.
Data from 126 unselected cases were gathered and tabulated (Table 1). The false-negative and falsepositive rates were 10 of 32 (31.3%), and 17 of 94 (18.1%) respectively. The predictive value of a surgical “positive” estimate was 22 of 39 (56.4%).
T
HE FIRST NATIONAL Wilms’ Tumor Study (NWTS-1) confirmed the observations by Jereb et al’ that lymph node (LN) metastases carried a greater risk of recurrence. A review of NWTS-2 and NWTS-3 patients with stage I to III tumors showed that of the 214 patients in whom LN were not examined or noted, there was a 12.6% relapse rate and 8.9% died. The rest&s were similar when the LN were pathologically negative in 1,067 patients: 13.8% relapsed and 8.6% died.2d With positive LNs confined to the renal hilum, the relapse rate increased to 22.4%, with death occurring in 13.8%. When the nodal involvement extended to the aortic or other LNs, relapses reached a high of 46.2%, with death in 39.6%. Therefore, all patients with positive LNs are now.placed in stage III.4 An earlier report from the NWTS-1 Surgical Committee showed a good concordance (96%) between the From the Medical Urnkersity Hospital, Charleston, SC; University of California. San Francisco, CA; West Virginia University, Morgantown, WV; Mayo Clinic, Rochester, MN; University of Wahington, Seattle, WA; and The Children’s Hospital of Philadelphia, Philadelphia, PA. For The National Wilms’ Tumor Stu& (NWTS) Group. Supported in part by USPHS Grant No. CA-42326. Principal investigators at participating institutions also receive independent supportfrom theNational Cancer Institute. Date accepted: February 17.1989. Address reprints requests to Giulio J. D;Qngio. MD. Department of Radiation Oncology, Hospital of the University of Pennsylvania. Philadelphia. PA I91 04. 8 1990 by W.B. Saunders Company. 0022-3468/90/2503-0014$03.00/0
330
MATERIALS
AND
METHODS
The cooperation of 31 pediatric surgeons and urologists was
enlisted. All patients coming under their care were to have complete LN sampling, and statements entered on a form as to whether they considered identifiable LNs to be positive or negative. The operative procedures were not radical LN dissections; rather, they were excisions of identifiable LNs, encountered in the periaortic regions, that did not accompany the excision specimen as part of a standard nephrectomy. RESULTS
DISCUSSION
The prognostic importance of positive LNs in Wilms’ tumor patients is well established, and has led some authorities to advocate radical node dissections in managing such children.6 Leape et al,’ in their review of patients entered in the first NWTS, could reach no conclusion regarding the possible value of formal LN dissections but stressed the need for adequate LN sampling. The more systematic investigation reported here confirms that need. An important consideration is how often the surgeon would have been wrong in not sampling a node he considered negative, That figure would seem to be about 11% in this study (10187) (Table 1). That is, 11% of patients would have been down-staged inaccurately to stage II, barring other criteria for stage III. By contrast, 44% (17/39) would have been erroneously up-staged on the surgeon’s estimate alone, and overtreated as a result. Perhaps an even more cogent consideration is the following: 126 patients underwent LN sampling. The surgeons made erroneous estimates both ways, but the LNs that were incorrectly assessed as positive were corrected by the pathologists. Since suspicious LN will always be biopsied, such patients will almost invariably be correctly staged. However, as many as 8% (10/126) might have been falsely down-staged if the surgeon had acted on his opinion and not sampled the node(s).
Journalof
Pediatric Surgery, Vol 25, No 3 blarch),
1990: pp 330-331
331
LYMPH NODES IN WILMS’ TUMOR
Table 1. Evaluation of Lymph Nodes by Surgeon and Pathologist Surgeon’s
Path&gist’s Positive
Evaluaion
Evaluation Total
Neeative
Positive
22
10
32
Negative
17
77
94
Total
39
a7
126
(This is a maximum figure, because some will have positive hilar nodes that come with the specimen. These will be identified by the pathologist, and stage. III will be assigned correctly.) The children would therefore not have received the more intensive treatment currently being advocated for stage III children;
ie, the addition of tumor bed irradiation (RT) and Adriamycin (ADR) to actinomycin D and vincristine. Neither RT nor ADR is used in stage II favorable histology (FH) tumor patients. The 4-year relapse-free and survival rates for stage III/FH patients treated with 1000 cGy RT and three drugs are 82% and 91%, respectively,very similar to the 87% and 91% recorded for corresponding end-points in stage II/FH children.7 ACKNOWLEDGMENT The authors gratefully acknowledge the contributions of 31 pediatric surgeons and pediatric urologists who contributed patients to this study. Their dedicated descriptions and lymph node biopsies were essential to this investigation.
REFERENCES 1. Jereb B, Tournade MF, Lemerle J: Lymph node invasion and prognosis in nephroblastoma. Cancer 45:1632-1636, 1980 2. Breslow N, Churchill G, Beckwith JB, et al: Prognosis for Wilms’ tumor patients with non-metastatic disease at diagnosisResults of the second National Wilms’ Tumor Study. J Clin Oncol 3:521-531, 1985 3. Unpublished Study. 4. Farewell
observations
VT, D’Angio
of the
GJ, Breslow
National
Wilms’
Tumor
N, et al: Retrospective
validation of a new staging system for Wilms’ tumor. Cancer Clin Trials4:167-171, 1981 5. Leape L, Breslow N, Bishop HC: The surgical treatment of Wilms’ tumor: Results of the National Wilms’ Tumor Study. Ann Surg 187:351-356.1978 6. Martin LW, Reyes PM, Jr: An evaluation- of 10 years’ experience with retroperitoneal lymph node dissection for Wilms’ tumor. J Pediatr Surg 4:683-xxx, 1969 7. D’Angio GJ, Breslow N, Beckwith JB, et al: The treatment of Wilms’ tumor: Results of the Third National Wilms’ Tumor Study. Cancer 64:349-360, 1989