Distribución de la temperatura y salinidad

was all the more striking in view of the fact that ICON1 harbored low-risk patients (stage Ia or Ib, grade 1) in 15% of cases, unlike the ACTION trial. This all leads to the conclusion that the vast majority of patients in the ICON1 trial should be considered as non-optimally staged.

By accepting this assumption it makes it easier to explain the benefits of adjuvant chemotherapy in terms of DFS and overall survival. To take this one step further, assuming that only a few ICON1 patients and only one-third of the ACTION patients were optimally staged, it is likely that not much more than one-sixth of the patients in the combined ACTICON population were optimally staged. This means that, by and large, 20%, or one out of every five patients, of the ACTION study group would have harbored residual tumor tissue following surgery. That figure explains the overall survival and DFS advantages of adjuvant chemotherapy in this group.

In conclusion, the ACTION and ICON1 trials have proved, beyond doubt, that adjuvant chemotherapy is effective for treating residual tumor deposits in supposed early ovarian cancer following non-optimal surgical staging. In this respect, chemotherapy serves to correct poor surgery. For optimally staged patients, the ACTION trial suggests that adjuvant chemotherapy is of little or no benefit. Withholding chemotherapy in these cases might be even more relevant in view of the reported superiority of tumor response to chemotherapy in chemo-naive patients [2] and the relatively high risk of second primary tumors in long-term survivors of early ovarian cancer.

RECOMMENDATIONS FOR TREATMENT

On the basis of the results of recent randomized trials in early ovarian cancer, a comprehensive and complete surgical staging should be pursued. This will diminish or exclude the risk of unnoticed residual disease, and, therefore, improve the prognosis of early-stage ovarian cancer. Achieving the goal of optimal surgical staging at the time of the first laparotomy often proves difficult in routine clinical practice. Patterns of care for this disease might be redefined as recently suggested by British investigators [29]. Policies for referral to oncology centers and the availability of consulting gynecological oncologists to perform staging procedures in community hospitals should be evaluated in this respect. Incompletely staged patients should be restaged unless physical or psychological factors indicate otherwise, in which case adjuvant chemotherapy should be given as it has proven effectiveness against residual tumor deposits. The number of courses is debatable. The ACTION and ICON1 trials recommended six courses. This

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number of courses seems the most logical since it is regarded as standard treatment for stage III ovarian cancer, and the risk of insufficiently treated stage III disease is the main reason for administering adjuvant chemotherapy.

What about giving adjuvant chemotherapy in optimally staged patients? The subgroup analysis of the ACTION trial strongly suggests that this does not improve overall survival and DFS and would, therefore, do more harm than good. Because this is the first time that this has been demonstrated, some practitioners will stick to the old policy of treating high-risk, early-stage ovarian cancer with adjuvant chemotherapy. There are several reasons why practitioners might resist changes to the standard treatment pattern: some might not be convinced by a single randomized trial; some might fear withholding a seemingly beneficial therapy to the patient; some might fear medico-legal complications in cases of tumor recurrence; and some might be unwilling to refuse the patient’s demands to ‘do everything that is possible’.

Nevertheless, advocates of the adjuvant chemotherapy policy should consider the harmful effect of unnecessary chemotherapy in terms of morbidity, costs, and impaired quality of life. Furthermore, the higher tumor response of recurrences in chemo-naive patients and the longterm risks of second primary tumors in survivors of ovarian cancer deserve consideration. Finally, it should be realized that in virtually all studies reporting risk factors and defining categories of high-risk patients, chemotherapy was given and this treatment did not diminish the high-risk status of these patients in any way.

REFERENCES

1. Young RC, Walton LA, Ellenberg SS, et al. Adju- vant therapy in stage I and stage II epithelial ova- rian cancer. Results of two prospective randomi- zed trials. N Engl J Med 1990; 332: 1021–1027. 2. Bolis G, Colombo N, Pecorelli S, et al. Adjuvant

treatment for early epithelial ovarian cancer: results of two randomised clinical trials compa- ring cisplatin to no further treatment or chromic phosphate (32P). G.I.C.O.G.: Gruppo Interregi- onale Collaborativo in Ginecologia Oncologica. Ann Oncol 1995; 6: 887–893.

3. Young RC, Decker DG, Wharton JT, et al. Staging laparotomy in early ovarian cancer. JAMA 1983; 250(22): 3072–3076.

4. Mc Gowan L, Lesher LP, Norris HJ, Barnett M. Misstaging of ovarian cancer. Obstet Gynecol 1985; 65: 568–572.

5 . Helewa ME, Krepart GV, Lotocki R. Staging la- parotomy in early epithelial ovarian carcinoma. Am J Obstet Gynecol 1986; 154: 282–286. 6. Buchsbaum HJ, Brady MF, Delgado G, et al. Sur-

gical staging of carcinoma of the ovaries. Surg Gynecol Obstet 1989; 169: 226–232.

7. Trimbos JB, Schueler JA, van der Burg M, et al. Watch and wait after careful surgical treatment and staging in well-differentiated early ovarian cancer. Cancer 1991; 7: 597–602.

8. Soper JT, Johnson P, Johnson V, Berchuk A, Clarke-Pearson DL. Comprehensive restaging la- pa rotomy in women with apparent early ovarian carcinoma. Obstet Gynecol 1992; 80: 949–953. 9 . Schueler JA, Trimbos JB, Hermans J, et al. The

yield of surgical staging in presumed early stage ovarian cancer: benefits or doubts? Int J Gynecol Cancer 1998; 8: 95–102.

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