16 The significance of lymph node status at pelvic, common iliac and para-aortic levels

16 The significance of lymph node status at pelvic, common iliac and para-aortic levels

16 The significance of lymph node status at pelvic, common iliac and para-aortic levels G. FERRARIS A. L A N Z A A. RE M. RASPOLLINI D. PROSERPIO R. B...

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16 The significance of lymph node status at pelvic, common iliac and para-aortic levels G. FERRARIS A. L A N Z A A. RE M. RASPOLLINI D. PROSERPIO R. BELLINO

The presence of lymph node metastases in the surgical specimen following total resection of cervical carcinoma is a major predictor of survival (Noguchi et al, 1987). However, random removal of a few nodes, or of only those suspected or palpable, is not enough since a by no means negligible percentage of error remains--as well as the possible presence of micrometastases (Averette et al, 1972; Blyte et al, 1986). In addition, some studies have made i~ clear that cervical carcinoma tends to skip-spread along the lymphatic system (Chung et al, 1980; Martimbeau et ai, 1982). Importance is also attached to the total number of metastatic nodes, their bilaterality, and the involvement of several locations. Radical systemic adenectomy is thus a sound procedure and is indeed essential for both diagnostic and prognostic purposes. Our surgical approach rests on three bases: (1) radical systemic pelvic adenectomy; (2) dissection of the presacral lamina; and (3) excision of the para-aortic nodes (Valle, 1970; Valle and Napolitano, 1970; Ferraris, 1977; Ferraris, 1978; Ferraris, 1979; Ferraris et al, 1988). This chapter examines the distribution of metastatic nodes in several levels and its relation to histoprognostic parameters such as invasion of the parametrium, vagina, corpus uteri and cervical canal, and deep infiltration of the cervical stroma and capillary-like spaces (CLS) (Abdulhayoglu et al, 1980; Chung et al, 1980; Boyce et al, 1981; Inoue and Okumura, 1984). MATERIALS AND METHODS

A total of 193 patients with Stage Ib-IVa cervical carcinoma were operated on at the Department of Gynaecology and Obstetrics (Section B), University of Turin, between January 1977 and March 1988. Removal of the para-aortic nodes and presacral lamina was not extended to Stage Ib cases until 1983, and was thus not performed in 56 cases. Our series was therefore Bailli~re's Clinical Obstetrics and Gynaecology--Vol. 2, No. 4, December 1988

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G. FERRARIS ET AL

composed of 137 patients, aged 22-68 years (mean 45 years), subjected to pelvic, presacral and para-aortic adenectomy: 40 Stage Ib patients, 17 Stage IIa patients, 66 Stage lib patients, 10 Stage III patients and 4 Stage IV patients. The number of metastatic nodes and their locations were determined in each case, together with the following parameters: invasion of the parametrium, vagina, corpus uteri and cervical canal, embolization of the CLS, infiltration of the cervical stroma and recurrences. The pathological distribution of the metastatic nodes was divided into three levels: level I (obturator and external iliac nodes); level II (common iliac and presacral nodes); level III (para-aortic nodes). RESULTS

Metastases were observed in 20% of Stage Ib cases, 29.4% of Stage IIa cases, 43.9% of Stage lib cases, 100% of Stage III cases and 75% of Stage IV cases, making a total of 55 cases (Table 1). One node was invaded in nine cases, two in 15 cases and three or more in 31 cases. Invasion was bilateral in 16/55 cases. Table 1. Clinical stage and lymph node involvement (n = 137).

Number of cases

Number without metastases

Ib

40

32

5

IIa

17

12

4

IIb

66

37

19

III

10

-

9

IV

4

1

2

137

82

39

Stage

Lymph node metastases unilateral bilateral

Rate of metastasis

3

20.0

1

29,4

10

43.9

1

100.0

1

75.0

16

40.1

8 5 29 10 3 Total

55 Table 2. Site of lymph node metastasis. *

Obturatory fossae External iliac Common iliac Presacral Para-aortic Total

Number of lymph nodes

Positive

Rate (%)

Number of cases

913 777 576 269 397

68 41 39 11 49

%4 5.3 6.8 4.1 12.3

30 21 17 8 18

2932

208

7.1

*Number of lymphadenectomies: 137. Number of lymph nodes: 2932. Mean number of lymph nodes per lymphadenectomy: 21.4.

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LYMPH NODE STATUS

Node metastasis sites are illustrated in accordance with the conventional topographical criteria in Table 2. Our distribution into three levels (Table 3) resulted in the identification of seven groups: 1. 2. 3. 4. 5. 6. 7.

Eighty-two patients (59.9%) with no metastatic nodes Twenty-three patients (16.8%) with level I invasion only Eight patients (5.8%) with level I and level II invasion Eight patients (5.8%) with level I, level II and level III invasion Six patients (4.4%) with level II invasion only Two patients (1.5%) with level II and level III invasion Eight patients (5.8%) with level III invasion Table

Group

Level I

3.

Distribution of lymph node positivity in the three levels. Level II

Level III

Number of cases

1

-

-

-

82

2 3 4 5 6 7

+ + + -

+ + + + -

+ + +

23 8 8 6 2 8

Nodal metastases (%) 0

41.8 14.5 14.5 10.9 3.6 14.5

The presence of pathological risk factors is illustrated in Table 4: 1. 2. 3. 4. 5. 6.

Infiltration of the parametrium: 37 patients (26.2%) Invasion of the vagina: 17 patients (12.4%) Invasion of the corpus uteri: 33 patients (24.0%) Invasion of the cervical canal: 35 patients (25.5%) Involvement of the external third of the cervix: 77 patients (56.0%) Involvement of the CLS: 29 (21.1%)

The statistical relationships between sites of metastasis and these histoprognostic factors show that only the relationship between presacral metastasis and the corpus uteri was significant (P<0.05) (Figure 1). The main factors (invasion of the parametrium, external third of the cervix and CLS) were correlated with the three metastasis levels (Figures 2, 3 and 4). Invasion of the parametrium (0.025-P--0.001), external third of the cervix Table 4. Relationship between stratification of population and pathological risk factors. External Corpus Cervical third of CapillaryParametrium Vagina uteri canal cervix like spaces (number of (number of (number of (number of (number of (number of cases) cases) cases) cases) cases) cases) Total NN+

9/82 27/55

Total Rate

37/137 26.2

9/82 8/55

16/82 17/55

24/82 11/55

42/82 35/55

10/82 19/55

82 55

17/137 12.4

33/137 24.0

35/137 25.5

77/137 56.0

29/137 21.1

137

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G. FERRARIS ET AL 100 " 89.7 I

48.2

35/39 l

>

o 50

49.1 27/55

19/39 30.1

o I---

15.4.

14.5

,,10.2, 5.5

p~

V~

C*

~4/39,

'6/39~

CLS*

CX*

2/5,5 CC*

P < 0.05

Figure 1. Correlation among prognostic factors and total lymph node metastases and sacral lymph node involvement. P+ parametrium involvement; V ~ vaginal involvement; C + corpus involvement; CLS + capillary-like space involvement; CX + involvement of the external third of the cervix; CC + cervical canal involvement; [ ] presacral lymph node positivity.

(0.01-P--0.001), and CLS (P<0.001) had a significant effect on the appearance of level I metastases (Figure 2). Figure 3 presents the correlation between the pathological factors and metastasization as far as level II. Invasion of the parametrium (P<0.001) and the external third of the cervix 100908070. "13

=o

6050-

E

54.5 43.7

4030-

_1

20" 10. 0

p+

i

3t .1

17.9

12.2 6.9

p-

0.025 < P <. 0.01

C× +

CX -

0.01 < P < 0.001

CLS +

CLS --

P < 0.(3,01

Figure 2. Correlation among the level I metastases (n = 23) and parametrium (P), the external third of the cervix (CX) and capillary-like space (CLS).

LYMPH NODE STATUS

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100" 9080" 70.

.E

6047.1

50-

E 40. z

3019.2

20: 7.6

10-

2.4 IN \ \

0

p+

p-

CX.+

~l

CX.-

0.025 < P < O.01

P < 0.001

Figure 3. Correlation among level II metastases and parametrium (P) and the external third of the cervix (CX).

(0.025-P-0.01) was significant in this respect. The percentage for the CLS was not significant, probably on account of the small number of cases examined. It is clear from Figure 4 that all the pathological factors were determinant for the appearance of level III invasion. 10090 80 70

70.6

o

60 50 E 40 g

28.6

30-

..J

20t2.5 t00

7.6

~

2.7 0

P+

P --

P < 0.001

CX.+

CX.-

0.025 < P < 0.01

I%'N \ N]

CLS +

CLS -

P < 0.01

Figure 4, Correlation among the level 1I[ metastases (n = 18) and parametrium (P), external third of the cervix (CX) and capillary-like spaces (CLS).

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The relationship between invasion of the parametrium, external third of the cervix and CLS (singly and variously combined) and distribution level is illustrated in Table 5. Uniform surgical management was applied with regard to two cases with level I and level II involvement. Comparison with level III, on the other hand, is rendered difficult by the fact that 12/18 patients were operated on at a time when radical surgery was excluded from the protocol, with the result that data for invasion of the stroma and the CLS are lacking. It was found that 30.4% of patients with level I metastases presented parametrial infiltration, nearly always accompanied by invasion of the stroma. In level II, invasion of the parametrium was observed in 57.1% cases, coupled with invasion of the stroma in 50%. Survival as a function of level is shown in Table 6. The data at 48 months are similar for levels I and II (48% and 42% respectively), whereas the figures for level II only and level III only are 26% and 17% respectively. The 48th month in the absence of metastases was 95%. An interesting finding, despite the small number of cases involved, is the 36-month survival of two subgroups of patients with level II or level III metastases subjected to palliative and radical surgery respectively: namely, 33.3% and 7.6% respectively. Table 5. Relationship between prognostic factors and distribution levels.

Parametrium Capillary-like spaces External third of cervix Parametrium + external third of cervix Capillary-like spaces + external third of cervix Parametrium + capillary-like spaces + external third of cervix

Level I (number of cases)

Level II (number of cases)

Level III (number of cases)

Total

2 1 6 2

4 5 2

10 1 1

16 1 12 5

8

1

3

12

3

2

1

6

Table 6. Relationship between survival rate and lymph node metastatic level. Months 0 12 24 36 48 60

N 0(%)

Level I (%)

Up to level II (%)

Level II alone (%)

Level II level III (%)

100 99.2 96.3 96.3 95.0 95.0

100.0 84.0 70.0 55.0 48.0 36.0

100.0 86.0 65.0 47.0 42.0 32.0

100.0 92.0 52.0 26.0 26.0 -

100.0 86.0 52.0 17.0 17.0 0.0

DISCUSSION A statistically significant relationship was clearly apparent between all our metastasis levels and the three histoprognostic factors (invasion of the parametrium, external third of the cervix and CLS). There is thus a distinct

LYMPH NODE STATUS

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relationship between these factors and the level of metastases. Invasion of the parametrium is associated with level I, II and III node involvement in 19.4%, 22.2% and 33.3% of cases, respectively, leaving 25.1% with no node metastases. These data, in spite of their limited differences, suggest that pre-operative determination of parametrial invasion could be a useful pointer to the risk of node metastasis at each level (Figures 2, 3 and 4) (see Chapter 13). It can also be deduced that if there is invasion of the para-aortic nodes (level III) and, even more so, level II invasion (57% of node positivity at level II with parametrial invasion), resection of the parametrium is mandatory, wherever possible, in view of the greater frequency of its invasion. Our findings (Table 5) suggest that in cases with level I metastasis, invasion of the parametrium is primarily the result of contiguity, whereas both contiguity and embolization are involved in level II cases, and embolization is mainly responsible in level Ill--subject to the reservations expressed with regard to the type of surgical management. The fact that the 48-month survival was much the same for level I only (48%) and level I or II (42%) is of interest, since 56.4% of those with node metastases fell within these categories. By contrast, the percentage of survival was much lower in cases with level II metastasis only (skip metastasis). This is further evidence of the fact that so-called paradoxical metastases indicate a poor prognosis and that there is a need for systemic adenopathy to secure a better outcome. Level III metastasis was accompanied by a further fall in 48-month survival to 17%, in line with the results of other workers (Averette et al, 1972; Piver and Barlow, 1974; Buchsbaum, 1979; Blyte et al, 1986). Of greater importance in this connection, in our opinion, is the observation that survival at 36 months was 33.3% following radical management compared with only 7.6% when surgery was confined to exploratory laparotomy and node biopsy (Table 7). It would thus seem advisable to adopt a radical approach when level III metastasization is evident. Our results and conclusions support the suggestion of Burghardt et al (1987) that adenectomy and radical surgery should be employed, despite the complications they may cause, for the purpose of preventing recurrences. Table 7. Survivalrate of patientswith levelII and level III

metastasis.

Surgicalpalliativetherapy Surgicalradicaltherapy

No evidenceof diseasefor 36 months 7.6% 33.3%

REFERENCES

AbdulhayogluG, Rich WM, ReynoldsJ & Di Saia PJ (1980) Selectiveradiationtherapyin Stage Ib uterine cervicalcarcinomafollowingradicalpelvicsurgery. Gynecologic Oncofogy 10: 84-92.

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G. FERRARIS ET AL

Averette HE, Dudan RC & Ford JH (1972) Exploratory celiotomy for surgical staging of cervical carcinoma. American Journal of Obstetrics and Gynecology 113: 1090-1096. Blyte JG, Hodel K, Wahl T et al (1986) Para-aortic node biopsy in cervical and endometrial cancer: does it affect survival? American Journal of Obstetrics and Gynecology 155: 306--314. Boyce JP, Fruchter RG, Nicastri AD et al (1981) Prognostic factors in Stage I carcinoma of the cervix. Gynecologic Oncology 12: 154-165. Buchsbaum HJ (1979) Extrapelvic lymph node metastases in cervical carcinoma. American Journal of Obstetrics and Gynecology 133: 814-824. Burghardt E, Pickel H, Haas J & Lahousen M (1987) Prognostic factors and operative treatment of Stages Ib to lib cervical cancer. American Journal of Obstetrics and Gynecology 156: 988-996. Chung CK, Nahhas WA, Stryker JA et al (1980) Analysis of factors contributing to treatment failure in Stages Ib and IIa carcinoma of the cervix. American Journal of Obstetrics and Gynecology 138: 550-556. Ferraris G (1977) L isterectomia radicale sec. Wertheim con linfadenectomia. Turin: Minerva Medica. Ferraris G (1978) Surgical Treatment oflnvasive Cervical Cancer. Abstract of the FIGO Kyoto Symposium, Satellite Meeting of the IXth World Congress of Gynecology and Obstetrics, Kyoto, November 1979, p 18. Ferraris G (1979) Conceptual Considerations of Wertheim's Radical Hysterectomy. Abstract of the IXth Congress of Gynecology and Obstetrics (FIGO) 1979, Tokyo, p 34. Ferraris G, Lanza A, D'Addato F et at (1988) Techniques of pelvic and para-aortic lymphadenectomy in the surgical treatment of cervical carcinoma. European Journal of Gynecologic Oncology 9: 83-86. Inoue T & Okumura M (1984) Prognostic significanceof parametrial extension in patients with cervical carcinoma Stages Ib, IIa and IIb. A study of 628 cases treated by radical hysterectomy and lymphadenectomy with or without postoperative irradiation. Cancer 54: 1714-1719. Martimbeau PW, Kjorsstad KE & Iversen T (1982) Stage Ib carcinoma of the cervix, the Norwegian Radium Hospital. It. Results when pelvic nodes are involved. Obstetrics and Gynecology 60: 215-218. Noguchi H, Shiozawa I, Sakai Yet al (1987) Pelvic lymph node metastasis of uterine cervical cancer. Gynecologic Oncology 27: 150-158. Piver SM & Barlow JJ (1974) Para-aortic lymphadenectomy in staging patients with advanced local cervical carcinoma. Obstetrics and Gynecology 43: 544-548. Valle G (1970) lntroduzione alia linfadenectomia ginecologica, vol. LIV, p 667. Milan: Societh Italiana di Ostetricia e Ginecologia. VaUe G & Napotitano C (1970) E giustificata una maggiore estensione della exeresi linfatica nel cervico carcinoma? Un procedimento sperimentale di linfadenectomia lombo-pelvica, vol. LIV, p 760. Milan: Societh Italiana di Ostetricia e Ginecologia.