Patterns of pelvic and paraaortic lymph node involvement in ovarian cancer

GYNECOLOGIC

ONCOLOGY

40, 103-106 (1991)

Patterns of Pelvic and Paraaortic Lymph Node Involvement in Ovarian Cancer ERICH BURGHARDT, M.D., FRANK GIRARDI, M.D., MANFRED LAHOUSEN, M.D., KARL TAMUSSINO, M.D., AND HARO STETTNER, PH.D.* Department of Obstetrics and Gynecology,

University

of Graz, Graz, and *Institute of Mathematics,

University

of Klagenfurt,

Klagenfurt,

Austria

Received January 25, 1990

lymphadenectomy in the course of primary surgical treatment. Seventy-five patients underwent only pelvic lymphadenectomy; in 105 patients lymphadenectomy was extended to include the paraaortic nodes. The last 21 patients in this series underwent a biopsy of the scalene lymph nodes before laparotomy. Unlike an earlier report [l], the patients in the present series were staged only on the basis of intraperitoneal findings, regardless of node status (Table 1). Lymphadenectomy was performed as in patients with cervical cancer. All lymphatic tissue was removed from in front of, behind, and between the iliac vessels up to the bifurcation of the aorta and down to the obturator fossa and the pelvic floor. Paraaortic lymphadenectomy extended up to the renal vessels, removing all lymphatic tissue around and between the aorta and vena cava. Twelve node groups were distinguished: external iliac, deep lateral external iliac, obturator, common iliac, deep lateral common iliac, sacral, and paraaortic. The nodes and attendant fatty tissue were fixed in formaldehyde, glacial acetic acid, alcohol, and distilled water for 24 hr. The material was processed en bloc as 600~pm serial sections. In 140 patients operated on before May 1987, both the number of positive individual nodes and the number of We describe pelvic and paraaortic lymph node involveinvolved node groups were noted. The size of nodal mement in 180 patients undergoing systematic lymphadetastases was measured in the largest section of each node, nectomies at primary surgery for ovarian cancer. One and expressed as one plus the logarithm of the product hundred forty patients were studied for number of inof the two greatest diameters; zero was allotted to mivolved nodes and node groups, size of nodal metastases, croscopic metastases. The number of involved node residual tumor, and survival. groups, the number of individual positive nodes, and the maximum size of the metastaseswere studied. All patients PATIENTS AND METHODS with stage IB to IV disease received platinum-based comBetween January 1980 and June 1989, 180 patients with bination chemotherapy. Life tables were computed by the stage I to stage IV ovarian cancer underwent systematic actuarial method and controlled by the log-rank test [2]. One hundred eighty patients with ovarian cancer underwent complete pelvic lymphadenectomy (n = 75) or pelvic and paraaortic lymphadenectomy (n = 105). Twenty-one patients underwent a preoperative biopsy of the scalene lymph nodes. The incidence of positive lymph nodes was 24% in stage I (n = 37), 50% in stage II (n = 14), 74% in stage III (n = 114), and 73% in stage IV (n = 15). Of the 105 patients who underwent pelvic and paraaortic lymphadenectomy, 13 (12%) had positive pelvic and negative paraaortic nodes and 10 (9%) had positive paraaortic and negative pelvic nodes. Positive scalene nodes were found in four patients (19%) later shown to have stage IV disease. One hundred forty patients were studied for number of involved nodes and node groups, size of nodal metastases, residual tumor, and survival. Of the 81 patients with positive nodes, most had only one or two positive node groups or one to three positive individual nodes. A few patients had seven to eight involved node groups with up to 44 positive nodes. Greater numbers of positive nodes were found in stage III than stage IV. The size of the largest nodal metastasis was not related to the clinical stage or survival, but did correlate with the number of positive nodes. Stage III patients with no residual tumor had a significantly lower rate of lymph node involvement than those with tumor residual (P < 0.01). Actuarial S-year survival rates of patients with stage III disease and no, one, or more than one positive nodes were 69, 58, and 28%, respectively. o IWI Academic PRSS, IX.

103 0090-X258/91 $1 SO Copyright 0 1991 by Academic Press, Inc. All rights of reproduction in any form reserved.

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BURGHARDT

ET AL.

TABLE 1 Node Involvement by Stage in 180 Patients Undergoing Lymphadenectomy for Ovarian Cancer Number of patients

Number of positive nodes (%I

I II III IV

37 14 114 15

9 (24) 7 (50) 84 (74) 11 (73)

Overall

180

111 (62)

Stage

TABLE 3 Results of Preoperative Scalene Node Biopsy in 21 Ovarian Cancer Patients Number of patients

Number positive

I III IV

2 13 6

0 0 4 (67%)

Total

21

4 (19%)

Stage

The size of the largest nodal metastasis did not differ significantly among the stages. Large metastases were RESULTS found even in stages I and II. The size of the largest nodal metastasis was not related to survival. With few excepOverall, positive lymph nodes were found in 111 (62%) tions, large metastases were found primarily in patients of 180 patients (Table 1). In stage III, 84 (74%) of 114 with numerous positive nodes. Stage III patients with no patients had positive nodes. Thirteen (12%) of 105 pa- postoperative tumor residual had a significantly lower rate tients undergoing both pelvic and paraaortic lymphade- of lymph node involvement than those with tumor residnectomy had only pelvic node involvement, while 10 ual (P < 0.01; Fig. 3). (9.5%) had positive paraaortic but negative pelvic nodes The actuarial 5-year survival of all patients with stage (Table 2). III disease is shown in Fig. 4. Patients with more than Of 27 patients with stage I or II disease, 5 (19%) had one positive node did significantly worse than those with positive paraaortic nodes, and 15 (29%) of 51 had positive no or one positive node (P < 0.05). The actuarial survival pelvic nodes (Tables 1 and 2). rates of patients with postoperative residual tumor and Preoperative scalene node biopsy showed positive no, one, or more than one positive node were 51, 56, nodes in 4 (19%) of 21 patients. All four patients were and 18%, respectively. The difference between patients found to have stage IV disease at subsequent laparotomy with one positive node and those with more than one (Table 3). approached statistical significance (P = 0.09). The surAmong the 140 patients analyzed further, most of the vival rates of patients with no residual tumor were 79, 81 with positive nodes had only one or two positive node 67, and 63%, respectively (P > 0.05). groups, but some had 7 or 8 (Fig. 1A). Similarly, most patients had only 1 to 3 positive nodes, but some had 30 to 44 (Fig. 1B). The distribution by metastasis size was DISCUSSION relatively uniform (Fig. 1C). In cervical cancer, lymph node involvement, the numFigure 2 shows the number of positive retroperitoneal nodes according to intraperitoneal stage. Patients with ber of involved node groups, and the diameter of the stage I or II disease had fewer positive nodes than those metastatic deposits are associated with survival [3]. The lymph node problem in ovarian cancer has received inwith more advanced disease. Some patients with stage III creasing attention only during the last 10 years [1,4-61, disease had by far more positive nodes than those with and the role of lymphadenectomy in this disease is constage IV disease. TABLE 2 Pelvic and Paraaortic Node Involvement According to Stage in 105 Patients Undergoing Pelvic and Paraaortic Lymphadenectomy for Ovarian Cancer Stage I II III IV Total

Number of patients

+ Pelvic + Paraaortic

+ Pelvic - Paraaortic

- Pelvic + Paraaortic

- Pelvic - Paraaortic

20 7 67 11

1 (5%) 3 (43%) 34 (51%) 8 (73%)

2 (10%) 1 (14%) 9 (13%) 1 (9%)

0 1 (14%) 9 (13%) 0

17 (85%) 2 (29%) 15 (22%) 2 (18%)

105

46 (44%)

13 (12%)

10 (9%)

36 (35%)

LYMPH

NODES

IN OVARIAN

105

CANCER

70

60 50 u L? 40 y:

30

POSITIVE NODE GROUPS 20 10 s:

0: <2cm

NED h-30)

a2-4 ;;f::ED

0

METASTASIS SIZE (LOG(MAX.SIZE)+l)

FIG. 1. (A) Number of involved node groups per patient. (B) Number of positive individual nodes per patient. (C) Size of largest lymph node metastasis expressed as log d,dl + I. One block represents one patient.

,n

,4

n: Im 0:

:.

0+..-----.-+---------+---------+---------+-.-------+ I0 20

30

40

50

40

50

40

50

NO. POSITIVE NODES

I

rf 5 z ;:

. nl

;: +‘.----.--+---------+---------+---------+---------+ 0 I0 20 NO.

POSITIVE

30 NODES

NO. POSITIVE NODES

2 IV

5 2

“; /.-2--.~--~?‘--‘-‘--+---------+---------+---------+ 0

I0

20

NODES INVOLVED

a>4

NODES INVOLVED

III disease.

POSITIVE NODES

F: El i=

:Nt%D

k39)

FIG. 3. Positive nodes and tumor residual in 91 patients with stage

30

20

I$

D

>2cm

h-22)

30

NO. POSITIVE NODES

FIG. 2. Stage and number of positive nodes per patient. One block represents one patient.

troversial. The spectrum of what is called lymphadenectomy ranges from cursory sampling for staging purposes to systematic removal of all accessible lymphatic tissue as a part of a debulking operation with a therapeutic intent. Lymphadenectomy in a large series of patients at our hospital raised the issue of the relationships between stage of disease and lymph node involvement and between node involvement and survival. The results of this series of ovarian cancer patients undergoing extensive lymphadenectomy confirm that lymph node involvement is more common in this disease than in other gynecologic cancers. Contrary to the concept of spread primarily to the region of the upper abdominal aorta and vena cava, the pelvic nodes were involved as often as the paraaortic nodes (Table 2). A possible tendency toward the pelvic region results only from the fact that 12% of the patients of all stages had positive pelvic but negative paraaortic nodes. The converse was true in only 9% (Table 2). The number of positive nodes was smaller in stages I and II than in stages III and IV, and highest in stage III (Fig. 2). Positive paraaortic nodes were found in 18% of patients with stage I and II disease (Table 2). Positive scalene nodes were found only in patients subsequently found to have stage IV disease. The 19% rate of scalene node involvement in 21 patients is similar to the 14% rate reported recently in a large autopsy study [7]. These findings suggest again that stages III and IV represent different patterns of spread [8]. Stage IV does not seem to develop out of stage III disease. Regarding the diameter of the lymph node metastases, there were no significant differences between the individual stages even though nodes of considerable size were removed in stages III and IV. The frequency of nodal involvement and the number of positive nodes were related to the resectability of in-

106

BURGHARDT

ET AL.

68.7%

(N-26)

--.... . .. .. .. .. . .. .. .. . ... . .. . .. . 2s,o%

(N15,)

---c;---e-4

“...,,

2 5 50 5 v)

‘L_

58,296 (N-(4)

*‘.a... A..*, -*-.. . . .. ... .. .

0 12

0 ----

0 NODE 1 NODE

24 INVOLVED INVOLVED

36 ..“‘....

48 >1 NODE

60 MONTHS INVOLVED

FIG. 4. Actuarial survival according to node involvement of all patients with stage III ovarian cancer.

traabdominal tumor masses (Fig. 3). Not surprisingly, patients with extensive intraabdominal disease that could not be completely debulked had more lymph node involvement than those with more limited disease and no residual tumor. Overall in stage III there was no significant difference in survival between patients with no or one positive nodes, but patients with more than one positive node did significantly worse (Fig. 4). The results of this series confirm the close relationship between intraabdominal tumor spread and lymph node involvement. Intraabdominal debulking remains of paramount importance for the outcome of patients with ovarian cancer. The issue of whether systematic lymphadenectomy prolongs the survival of patients with ovarian cancer remains open. But the rate of pelvic and paraaortic lymph node involvement in this disease is high, and chemotherapy seemsineffective in eradicating tumor deposits in the nodes [9-131. Lymph node involvement thus remains a central problem in the surgical management of ovarian cancer. REFERENCES 1. Burghardt, E., Pickel, H., Lahousen, M., and Stettner, H. Pelvic lymphadenectomy in operative treatment of ovarian cancer, Amer. J. Obstet. Gynecol. 155, 315-319 (1986). 2. Kalbfleisch, J. D., and Prentice, R. L. The statistical analysis of failure time data, Wiley, New York (1980). 3. Burghardt, E., Pickel, H., Haas, J., and Lahousen, M. Prognostic factors and operative treatment of stages IB to IIB cervical cancer, Amer. J. Obstet. Gynecol. 156, 988-996 (1987).

4. Burghardt, E., Lahousen, M., and Stettner, H. The role of lymphadenectomy in the treatment of ovarian cancer, in Ovarian cancerThe way ahead (F. Sharp and W. P. Soutter, Eds.), Royal College of Obstetricians and Gynaecologists, London (1987). 5. Burghardt, E., Lahousen, M., and Stettner, H. The significance of pelvic and paraaortic lymphadenectomy in the operative treatment of ovarian cancer, Bailke’s Clin. Obstet. Gynaecol. 3, 157-16.5 (1989). 6. Burghardt, E., Lahousen, M., and Stettner, H. The role of lymphadenectomy in ovarian cancer, in Ovarian cancer: Biological and therapeutic challenges (F. Sharp, W. P. Mason, and R. E. Leake, Eds.), Chapman & Hall, London, pp. 425-433 (1990). 7. Rose, P. G., Piver, M. S., Tsukada, Y., and Lau, T. Metastatic patterns in histologic variants of ovarian cancer: An autopsy study, Cancer 64, 1508-1513 (1989). 8. Pickel, H., Lahousen, M., Stettner, H., and Girardi, F. The spread of ovarian cancer, BailZiPre’s Clin. Obstet. Gynaecol. 3,3-12 (1989). 9 Creasman, W. T., Abu-Ghazaleh, S., and Schmidt, H. J. Retroperitoneal metastatic spread of ovarian cancer, Gynecol. Oncol. 6, 447 (1978). IO. Averette, H. E., Lovecchio, J. L., Townsend, P. A., Sevin, B. U., and Girtanner, R. E. Retroperitoneal lymphatic involvement by ovarian carcinoma, in Cancer campaign. Carcinoma of the ovary (E. Grundmann, Ed.), Fischer, Stuttgart (1983). Il. Wu, P. C., Qu, J. Y., Lang, J. H., Huang, R. L., Tang, M. Y., and Lian, L. J. Lymph node metastases of ovarian cancer: A preliminary survey of 74 cases of lymphadenectomy, Amer. J. Obstet. Gynecol. 155, 1103 (1986). 12. Burghardt, E., and Winter, R. The effect of chemotherapy on lymph node metastases in ovarian cancer, Baillit?res Clin. Obstet. Gynaecol. 3, 167-171 (1989). 13. Tulusan, A. H., Adam, R., Reinhardt, M., Atanasov, N., Thyselius, D., Merkle, E., Jlger, W., and Lang, N. Lymph node metastasis in epithelial ovarian cancer, in Ovarian cancer: Biological and therapeutic challenges (F. Sharp, W. P. Mason, and R. E. Leake, Eds.), Chapman & Hall, London, pp. 443-445 (1990).