GYNECOLOGIC ONCOLOGY 18, 293-298 (1984)

Stage III Epithelial Ovarian Cancer: The Role of Maximal Surgical Reduction

GREGORIO DELGADO, M.D.,’ DAVID H. ORAM, MRCOG, AND EDMUND S. PETRILLI, M.D.

Division of Gynecologic Oncology, Georgetown University Medical School, 3800 Reservoir Road, NW, Washington, D.C. 20007

Received March 18, 1983

One hundred forty-two cases of ovarian cancer of epithelial origin treated at Georgetown University Hospital between 1974 and 1980 were anafyzed. Seventy-five patients (52.8%) were found to have Stage III disease at the time of the initial laparotomy, and the purpose of this study was to assess the outcome of the management in this group of patients. In spite of an aggressive approach, complete tumor excision could only be affected in 13 of the 75 Stage III cases (17.3%). Residual disease of less than 2 cm was achieved in a further 8 cases (10.7%). The ability to perform complete tumor clearance bore no relationship to the grade of the tumor. The survival rate in the complete clearance group was 100% with a mean survival time of 45 months (range IO-90 months) and 10 of these patients have been shown to be free of disease by second-look laparotomy. The outcome in terms of survival and disease-free status in these two groups of patients was unaffected by various chemotherapy regimens and the only factor of importance appeared to be the success of the initial surgery in clearing the disease.

INTRODUCTION

Complete tumor removal at the time of initial laparotomy is a more or less established principle in the management of ovarian cancer [l-3]. Approximately 50% of all cases of ovarian malignant disease, however, have progressed to FIG0 Stage III by the time of presentation [4]. Recent reports from the M.D. Anderson Hospital demonstrate a vastly improved survival rate in Stage III ovarian disease following total tumor excision [5]. However, primary surgery in the majority of cases was performed in another institution and information was obtained from referring physicians. Griffith reports similar results in some of the cases with residual mass less than 1 cm. Review shows these cases had previous chemotherapy or recurrent cancer at the time of their surgery. However, in spite of the widely held belief in this surgical ideal the overall prognosis for 5-year survival remains variously quoted at 5% [6], 7% [71, or 12% [8].

One of the reasons for this poor survival rate may well be that further total tumor reduction in this group is only rarely possible. Further, when complete tumor removal may be achieved, this may be a reflection of a less virulent

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294 DELGADO, ORAM, AND PETRILLI

disease process. To clarify these points, a review of the management of Stage III ovarian cancer was performed and the outcome of such management was examined.

MATERIALS AND METHODS

One hundred forty-two consecutive cases of epithelial ovarian cancers treated at Georgetown University Hospital (GUH) between the years of 1974 and 1980 were reviewed. All patients were operated on by a single surgeon (G.D.) and an aggressive surgical approach was adhered to. Surgical staging by exploratory laparotomy which included peritoneal washings and paraortic and pelvic node sampling was performed in all cases, and the tumors were histologically graded.

Second-look laparotomies included cytologic washings, inspection of the omen- turn, and visualization of all peritoneal surfaces, multiple random biopsies, and retroperitoneal sampling of pelvic and paraaortic nodes. Patients with ovarian tumors that were not primary malignancies or were not of epithelial origin and cases where the initial surgery was not performed at GUH were excluded from this study.

RESULTS

Of the 142 cases reviewed, 75 (52.8%) presented with FIG0 Stage III disease at the time of the initial staging laparotomy. Table 1 shows the breakdown of the cases by stage, and in accordance with other studies, 65% of the patients were found to have disease outside the pelvis at the time of diagnosis.

The histologic grade of the tumor within the four stages is shown in Table 2. There appeared to be a predominance of more poorly differentiated tumors presenting in the more advanced stages of the disease. The relationship between grade and stage was subjected to analysis. A significant connection between increasing grade and increasing stage was demonstrated (P = <O.OOl).

Patients with Stage III disease were divided into three groups. Group A consisted of patients in whom complete tumor removal had been achieved. Group B included patients in whom the residual disease was less than 2 cm and Group C comprised

TABLE 1 STAGE OF DISEASE AT INITIAL LAPAROTOMY

Stage Number of cases %

I A B C

II A B C

III

IV

17 4 9

2 13

75

21

142

11.97 2.8 6.34

1.4 9.15 0.7

52.8

14.78

Total

MAXIMAL SURGICAL REDUCTION 295

TABLE 2 GRADE OF TUMOR WITH STAGE

Grade

l Stage I II III Total

I 21 5 4 30 II 5 3 8 16 III 12 29 34 75 IV 0 5 16 21

Total 142

patients in whom bulk disease greater than 2 cm remained at the end of surgery. Complete tumor removal could only be affected in 13 (17.3%) cases. Optimal cytoreductive surgery leaving residual disease where the largest tumor deposit was less than 2 cm diameter was achieved in a further 8 patients (10.7%). The remaining 54 patients all had residual disease of greater than 2 cm.

The success of maximal surgical reduction was not exclusively determined by tumor grade, as shown in Table 3, where eight patients in whom optimal results were obtained had histological Grade III tumors.

Table 4 describes survival time after surgical resection. The survival rate in Group A (NRD) was 100% with a mean survival time of 45 months (range lo- 90 months). In Group B (~2 cm) again, all patients are alive with a mean survival time of 44.5 months (range 6-62 months). In Group C (>2 cm) 35 patients are dead, one patient dying of other causes, and the mean survival time was 15.9 months, with no patients surviving longer than 43 months. Nineteen patients in this group are alive with a mean survival time of 19.2 months (range 6-59 months).

Table 5 describes the type of surgical procedure that was performed in order to affect either total tumor clearance in Group A or maximal surgical reduction in Group B. Two patients in Group A had had previous hysterectomies. In three cases in Group A and in a further three cases in Group B, bowel resection was necessary and one patient in Group A required a partial vaginectomy in order to achieve minimal or no residual disease. It should be emphasized at this time that in each case in Groups A and B where optimal surgical results were obtained,

TABLE 3 GRADE OF TUMOR WITHIN EACH STAGE III GROUP

(N = 75)

Group

Grade

I II III

Total

A (NRD) B (<2 cm) C (>2 cm)

4 2 6 5 2 22 4 4 26

13 8 54

296 DELGADO, ORAM, AND PETRILLI

TABLE 4 SURVIVAL TIME AFTER SURGICAL RESECTION

Group

A (NRD) B (<2 cm) ’ C (>2 cm)

Total No. patients 13

Alive NED (post second look) Residual tumor

(post second look) Clinically free disease

(no second look) Alive with evidence

of disease

13 (100%) 10 (76%)

0 (0%)

3 (24%)

Mean survival time (months) Range

0 (0%)

45 10-90

8 54

8 (100%) 19 (35%) 4 (50%) 0 (0%)

4 (50%) 0 (0%)

0 (0%) 0 (0%)

4 (50%) 19 (35%)

44.5 15.9 6-62

radical pelvic tumor dissection was necessary. This included retroperitoneal exploration, ureteral dissection, identification and exposure of the paravesical and pararectal spaces, as well as extensive serosal dissection of small and large bowel. The procedure, though stated simply in Table 4 as TAH and BSO, was often the equivalent in complexity to a radical hysterectomy.

The chemotherapeutic regimens employed in Groups A and B are shown in Table 6. Six patients in Group A and three patients in Group B were treated with a single alkylating agent; the remaining patients in both groups were randomly allocated to the various combination modalities shown.

Second-look operations have been performed in 10 of the 13 cases in Group A and all have proved negative. One patient declined second-look surgery but is clinically free of disease, and two other patients are awaiting second-look procedures and again are clinically free of disease. All eight patients in Group B have undergone second-look laparotomies. Four patients were found to be

TABLE 5 SURGICAL PROCEDURES IN GROUP A (NRD) AND GROUP B(< 2 cm)

Number of patients

Procedure Group A Group B

TAH-BSO,” paraaortic lymphadenectomy, omentectomy BSO, paraaortic lymphadenectomy, omentectomy TAH-BSO, paraaortic lymphadenectomy, omentectomy Sigmoid colectomy TAH-BSO, paraaortic lymphadenectomy, omentectomy Partial vaginectomy

Total

7 5 2 - 3 3

- - 1

- -

13 8

y All patients required radical tumor dissection.

MAXIMAL SURGICAL REDUCTION 297

TABLE 6 CHEMOTHERAPY IN GROUP A (NRD) AND GROUP B

(<2 cm)

Number of patients

Regimen Group A Group B

Melphalan 6 3 Hexamethylmelamine - - SFluorouracil 3 4 Cyclophosphamide - - &-Platinum - - Adriamycin 3 1 Cyclophosphamide - - Vincristine - - Adriamycin 1 - Cyclophosphamide - -

Total 13 8

free of disease and four patients had residual tumor. In the four patients who had negative second-look procedures, no relationship could be established between this complete response and either the grade of the original tumor or the type of chemotherapy regimen used. No patient in either group who was deemed to be disease free at the time of second-look laparotomy has subsequently shown evidence of tumor recurrence, the mean duration of follow up being 3 1.6 months (range 6-59 months).

DISCUSSION

This study shows that in spite of an aggressive surgical approach, optimal tumor reduction could only be achieved in 28% of cases of stage III ovarian cancer. It is therefore in contrast to other reports which place this figure much higher [9]. If complete tumor removal could be achieved, however, the prognosis was invariably excellent. This fact was not influenced either by the histologic grade of the tumor or by the type of chemotherapy employed. Because of this finding, it seems reasonable to suggest that single agent chemotherapy should be used as an adjunct to surgery in patients who have had complete tumor removal.

As over half the cases of ovarian cancer present as Stage III disease and because, as this study shows, the primary surgery is the singularly most important factor in determining prognosis, it should be stressed again that every effort should be made to effect total tumor clearance. Although this often involves tedious and time-consuming dissection, we would submit that this is essential if even 29% optimal results are to be obtained. Such perserverance should also be practiced because, as has been cited previously, tumors that at first appear nonresectable often provide surprising surgical rewards which manifest themselves as improved duration and quality of life for the patient.

298 DELGADO, ORAM, AND PETRILLI

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