Axillary lymphadenectomy—just how radical should it be?

Surgical Oncology 1996; 5: 37-41

Axillary lymphadenectomy-just how radical should it be? J. Ch. RAGETH,* P. WYSS,t C. UNGER* AND U. HALLERt *Spital iimmsttet, Gynakologie und Geburtshilfe, CH-8953 Schlieren; and tUniversitatsspital Zurich, Departement fur Frauenheilkunde, CH-8006, Zurich, Switzerland

To determine whether local axillary recurrences correlate with the number of lymph nodes extirpated, 779 cases of breast cancer were analysed in retrospect. Results: The number of lymph nodes extirpated varied between 1 and 42 per axilla. The axillary recurrence rate of 5.5% showed a minimal correlation between the frequency of these recurrences and the number of lymph nodes removed. There is an equally insignificant correlation between the percentage of positive histological findings and the number of lymph nodes extirpated: The trend analysis shows that with fewer than five lymph nodes extirpated, 40% of positive histological findings can be expected, whereas with over 20 lymph nodes extirpated the percentage is 45%. Conclusion: The number of lymph nodes extirpated is an unsuitable indicator as to how radical axillary clearance is. Surgeons should rely on anatomical boundaries rather than focusing on the number of lymph nodes removed. Surgical Oncology 1996; 5: 37-41. Keywords: axillary clearance, axillary lymphadenectomy, axillary recurrence.

to the pectoralis minor muscle). The number of lymph nodes extirpated corresponds to a certain extent to the degree of axillary lymphadenectomy performed. However, this number also depends on individual anatomical variations, and on the pathologist's accuracy when identifying individual lymph nodes from a specimen. This study aims to answer the following two questions: (i) Is it possible to reduce the frequency of axillary recurrences by removing more lymph nodes? (ii) Does the percentage of positive axillary lymph node findings correlate with the number of lymph nodes extirpated? This retrospective study did not examine any correlation between the morbidity and the number of lymph nodes extirpated.

INTRODUCTION The status of axillary lymph nodes is the most important independent prognostic factor for breast cancers, at least whilst other (biological) markers have not been sufficiently developed. Axillary lymphadenectomy is also, however, an important factor of morbidity [1-6]: reduced mobility of the shoulder joint, formation of an arm oedema, loss of motive force in the operated arm, sensibility disorders in the axilla and post-operative wound-healing impairment (serornas, infections) are complications to be mentioned. Limiting the extent of axillary dissection should be expected to reduce morbidity [7], but there are fears that falsenegative histological findings of lymph node status and axillary recurrences might increase. According to Berg [8] the axillary lymph node/ fatty tissue below the axillary vein can be classified into three levels (level 1: nodes lateral to the pectoralis major muscle; level 2: nodes dorsal to the pectoralis minor muscle; level 3: nodes medial

PATIENTS AND METHODS Between 1970 and 1990, 1042 patients with breast cancer were treated at the Gynaecological University Hospital, Zurich, SWitzerland. The latest tumour register update was in spring 1995 and the median observation period was 6.7 years at that time.

Correspondence: Dr J. Ch. Rageth, Gvnakoloqie und Geburtshiite, Spital Limmattal, Urdorferstr. 100, CH-8952 Schlieren, Switzerland. © 1996 Blackwell Science Ltd

37

J. Ch. Rageth et al.

38

Table 1. Average number of lymph nodesexcised per axilla and year of surgery

Year

No. of lymph nodes

1971 1972 1973 1974 1975 1976 1977 1978 1979 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990

5 7 5 8 8 7 5 6 10 11 10 10 12 13 12 15 15 18 19 19

Tumour follow-up was conducted either in the hospital's own tumour out-patient department or at general practices whose doctors were regularly asked if their patients were still tumour-free. The percentage of positive histological findings in the axilla and axillary recurrences, as well as the conclusions to be drawn were determined. Special statistical methods for group comparisons were therefore not required. In order to examine the correlation between axillary recurrences, histological involvement, and the number of lymph nodes extirpated, we used a linear-trend analysis by the least squares method. The straight trend line in the diagram is represented by the following equation: y = mx + b, whereby m corresponds to the ascending straight line, and b to the intersection with the y-axis.

RESULTS Of the 1042 patients, 330 died of the carcinoma, and 182 of other causes within the observation period. 229 are considered lost to follow-up (last check over 1 year ago). 425 patients are recurrence-free in the tumour follow-up and 51 are being checked, but have a tumour recurrence.

Table 2. Formation of an axillary recurrence as a function of the number of lymph nodes extirpated. All patients with a known number of extirpated and involved lymph nodes (n = 779) irrespective of whether their lymph nodes had been involved or not at the time of the first surgery

Number of lymph nodesextirpated

n

Axillary recurrences (%)

1-4 5-6 7-8 9-10 11-12 13-15 16-20 21-42

57 81 97 94 89 134 150 77

5.3 4.9 5.2 7.4 6.7 6.0 4.7 3.9

Total (0-42)

779

5.5

Table 1 shows the average number of lymph nodes extirpated per axilla and year of surgery. 779 patients had both their number of lymph nodes extirpated and the number of lymph nodes involved accurately documented. In the remaining 263 cases, no axillary lymphadenectomy was performed at all, or the precise number of extirpated and involved lymph nodes was not determined. This was particularly true for earlier years (up to 1973). Table 2 shows, for all patients reviewed, the correlation between the percentage of axillary recurrences and the number of lymph nodes extirpated. Table 3 shows this percentage for the nodalnegative patients (n = 433; 2.1 % of axillary recurrences) and Table 4 the percentage for nodalpositive patients (n = 346; 9.8% of axillary recurrences). The results from Tables 2-4 suggest that there is no clear correlation between the frequency of axillary recurrences and the number of lymph nodes extirpated. However, there was no axillary recurrence in the nodal-negative group if over 15 lymph nodes had been removed. Table 5 shows the clinical characteristics of the nodal-negative patients with an axillary recurrence and Table 6 lists the olinical characteristics for the nodal-positive patients with an axillary recurrence. As can be seen, three patients had over 20 lymph nodes removed and still developed an axillary recurrence. Figure 1 shows the proportion of the number of lymph nodes extirpated to the percentage of lymph ©1996 Blackwell Science Ltd, Surgical Oncology, 5: 37-41

39

Axillary lymphadenectomy-how radical? Table 3. Formation of an axillary recurrence as a function as a function of the number of lymph nodes extirpated . Nodal-negative patients (n = 433) Number of lymph nodes extirpated

1-4 5-6 7-8 9-10 11-12 13-15 16-20 21-42 Total (0-42)

n

Axillary recurrences (%)

44

0.0 4.2 3.8 1.8 2.2 4.0 0.0 0.0

433

2.1

30 48 53 55 46 75 82

Table 4. Formation of an axillary recurrence as a function as a function of the number of lymph nodes extirpated . Nodal-positive patients (n = 346) Number of lymph nodes extirpated

1-4 5-6 7-8 9-10 11-12 13-15 16-20 21-42 Total (0-42)

n

Axillary recurrences (% )

27 33 44 39 43 59 68 33

11.1 6.1 6.8 15.4 11.6 8.5 10.3 9.1

346

9.8

nodes involved. The trend line in this figure suggests that the percentage of positive histological findings is slightly higher if more lymph nodes are found in the lymphadenectomy specimen.

DISCUSSION Over a number of years, an increasing number of lymph nodes per axilla were found in histological examinations (Table 1). It has to be mentioned, however, that lymph nodes were not counted at all at the beginning of the study period; counting started in 1972. Furthermore, lymphadenectomy procedures tended to be performed more radically in the 1980s, by which time the pathologists' accuracy when processing extirpated tissue had also improved. The increase in the number of lymph nodes extirpated is therefore only slightly due to the more radical surgical technique.

©1996 Blackwell Science Ltd, Surgical Oncology, 5: 37-41

Table 5. Clinical characteristics of the nine nodal-negative patients with an axillary recurrence Age (years)

Number of lymph nodes extirpated

Years to an axillary recurrence

52 30

6 6 7 7 9 12 13 14 14

2.2 9.4 3.5 2.3 1.4 5.5 2.2 0.2 1.7

44

42 69 55 50 89 52

With our patient population we did not succeed in determining a limit for the number of lymph nodes to be removed beyond which the number of axillary recurrences can be expected to be considerably lower. We also failed to show a clear correlation between the percentage of positive axillary histological findings and the number of lymph nodes extirpated. Other authors, however, were more successful in proving such a correlation. Graverson et al. (9) calculated the probability of an axillary recurrence after 5 years for various categories: (i) with no lymphadenectomy there is a probability of 19%, (ii) with 1-2 lymph nodes removed it is 10%, (iii) with 3-4 lymph nodes extirpated it is 5%, and (iv) with 5-10 lymph nodes merely 3%. Even with over 10 lymph nodes extirpated, the calculated percentage of this Danish study remains at 3% of axillary recurrences after 5 years. Axelsson et al. (10) examined 13,851 patients with breast cancer in the Danish cancer register and found that the time up to which axillary recurrences appeared was markedly prolonged if over 10 lymph nodes had been removed . Verones i et al. (11), Muller et al. [12), Senofsky et al. [13) and Danforth et al. (14) examined the skipping phenomenon (discontinuous spreading of lymph node involvement-skipping of lymph node stages). By limiting the axillary lymphadenectomy to level 1, false-negative axillary staging would have occurred in 1.5% (Veronesi et al.), in 2% (Muller et al.) and in 29% (Senofsky et al.) of the Iymphadectomies performed. Levels 1 and 2 had been skipped (i.e, metastases occurred in exclusively level 3) in 2.6% (Senofsky et al.), in 0.2%

J. Ch. Rageth et al.

40

Table 6. Clinical characteristics of the 34 nodal-positive patients with an axillary recurrence

Age (years)

74 60

Number of lymph nodes extirpated

Numberof lymph nodes involved

Years to an axillary recurrence

1.5 7.3

1

1

69

2 4

1 4

4.2

51

5

65

6

3 3

1.4 6.6

59 59 59 71 57 35

7 8 8 9 9

10 10 10 10

55

54 52 60 54

11 11

12 12 12 13 14 14 14 15

63

70 94 64 67

72

77 44

60

16 16 16

83

71 57 44 60 31 47

17 19 19 19 22 31

55

33

76

2

5.8

2

0.7 1.4 1.4 1.0 9.1 0.4 1.7

4

2 8 1 1 6

10 2

0.2 2.6 4.2

4 4

0.1

6

7.2

12 9

2.1 11.4

1

8.8

8 14

2.1 0.3

5 1

3.6

12 14 17 9

17 17 7 27 18

1.7 1.1

0.4 1.6

0.5 0.9 2.3 2.0 2.0

3.7

(Muller et al.) and in as many as 20% (Danforth et al.) of the cases examined. Differentiating between

the three levels seems somewhat arbitrary in view of such enormous differences. Indeed, it is not very easy to determine clear boundaries between levels 1 and 2 during the operation, since even a slight tug may cause a large part of level 2 lymph nodes to be pulled lateral the pectoralis minor muscle. Pigott et al. [15) divided the axilla into lower and upper levels, which is of interest since the extirpation of the upper lymph nodes is said to contribute most to morbidity [7). Pigott et al., however, found metastases occurring exclusively in the upper level in 32% with clinically negative findings. It appears that breast cancers, in medial positions in particular, tend to metastasize into the upper lymph node group. In this paper the number of lymph nodes removed did not greatly affect histological positivity and axillary recurrence. Regardless of the number of lymph nodes extirpated, the percentage of positive axillary findings was between 40% and 45% and the frequency of axillary recurrences was 5.5% after a median observation period of 6.7 years. Furthermore, experience has shown that although the technique remains unchanged, the number of lymph nodes extirpated may vary considerably; in the last few years J.Ch.R. has removed between 8 and 42 lymph nodes per axilla, always using the same technique. It also has to be said that the pathologist's accurate macroscopic preparation of the lymph nodes from the excised material and the microscopic processing of the nodes (serial sections) can

100 Q.l

> 80

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'iii

0 Co

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60

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Figure 1. Proportion of the number of

0 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 37 40 Number of lymph nodes extirpated

lymph nodesextirpated to the percentage of the lymph nodes involved. 779 axillary Iymphadectomies 1970-1990: 434 (55.7%) negative and 345 (44.3%) positivefindings.

© 1996 Blackwell Science ltd, Surgical Oncology, 5: 37-41

Axillary lymphadenectomy-how radical?

help to avoid false-negative findings to a considerable extent [16]. Since the number of lymph nodes per axilla can

7.

vary considerably from one case to another and the macroscopic-microscopic

examinations

of

the

axillary lymph node fatty tissue pad are often performed in various ways, the number of lymph nodes extirpated is an unsuitable indicator as to how

radical

is

the

axillary

lymphadenectomy;

8. 9.

surgeons would do better to rely on anatomical boundaries. In accordance with other studies [12, 10] we recommend the radical axillary lymphade-

10.

nectomy of level 1 and 2 lymph nodes (and of level 3 with palpable lymph nodes). This procedure is indispensable for accurate staging and helps to prevent axillary recurrences. We advise against the

11.

use of reduced procedures such as the so-called sentinel lymphadenectomy (17).

12.

REFERENCES 13. 1. Aitken RJ, Gaze MN, Rodger A, Chetty U, Forrest APM. Arm morbidity within a trial of mastectomy and either nodal sample with selective radiotherapy or axillary clearance. Br J Surg 1989; 76: 568-71. 2. Bratschi HU, Haller U. Die Bedeutung des Nervus intercostobrachialis bei der axillaren Lymphonodektomie. Geburtsh Frauenheilk 1990; 50: 689-93. 3. Hladiuk M, Huchcroft S, Temple W, Schnurr BE. Arm function after axillary dissection for breast cancer: a pilot study to provide parameter estimates. J Surg Oneo/1992; 50(1): 47-52. 4. Hoe AL, Iven 0, Royle GT, Taylor I. Incidence of arm swelling following axillary clearance for breast cancer. Br J Surg 1992; 79(3): 261-2. 5. Ivens 0, Hoe AL, Podd TJ, Hamilton CR, Taylor I, Royle GT. Assessment of morbidity from complete axillary dissection. Br J Cancer 1992; 66(1): 136-8. 6. Menton M, Roemer V. Serombildung und

© 1996 Blackwell Science Ltd, Surgical Oncology, 5: 37-41

14.

15.

16.

17.

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Drainagetechnik nach Mastektomie. Fortsehr Med 1990; 108: 350-2. Larson 0, Weinstein M, Goldberg I, et al. Edema of the arm as a function of the extent of axillary surgery in patients with stage I-II carcinoma of the breast treated with primary radiotherapy. Int J Radiation Oneal BioI Phys 1986; 12: 1575-82. Berg JW. the significance of axillary node levels in the study of breast carcinoma. Cancer 1955; 8: 776-8. Graversen HP, Zedeler K, Andersen JA, Axelsson CK, Blichert Toft M. Axillary dissection in primary surgical treatment of breast cancer: risk of false-negative axillary status. Ugeskr Laeger 1992; 154(48): 3392-5. Axelsson CK, Mouridsen HT, Zedeler K. Axillary dissection of level I and II lymph nodes is important in breast cancer classification. The Danish Breast Cancer Cooperative Group (DBCG). Eur J Cancer 1992; 28A(8-9): 1415-8. Veronesi U, Rilke F, Luini A, et al. Distribution of axillary node metastases by level of invasion. Cancer 1987; 59: 682-7. Muller A, Mattfeld T, Engel K, Schmidt W, Bastert G. Untersuchungen zur Hadikalitat der axillaren Lymphonodektomie. Geburtsh Frauenheilk 1990; 50: 524-7. Senofsky GM, Moffat FL Jr, Davis K, et al. Total axillary lymphadenectomy in the management of breastcancer.ArehSurg 1991; 126(11): 1336-41. Danforth 0, Findlay PA, McDonald HD, Lippman ME, Reichert CM, D'Angelo T, Gorell CR, Gerber NL, Lichter AS, Rosenberg SA, DeMoss ES. Complete axillary lymph node dissection for Stage I-II carcinoma of the breast. J Clin Oneal 1986; 4(5): 655-62. Pigott J, Nichols R, Maddox WA. Metastases to the upper levels of the axillary nodes in carcinoma of the breast and its implications for nodal sampling procedures. Surg Gyneeol Obstet 1984; 158: 255-9. International Breast Cancer Study Group. Prognostic importance of occult axillary node micrometastases from breast cancer. Lancet 1990; 335: 1565-8. Giuliano AE, Kirgan OM, Guenther JM, Morton DL.; Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg 1994; 220(3): 391-8.