OBGYN.net Conference Coverage2000 INTERNATIONAL FEDERATION of GYNECOLOGY & OBSTETRICS: Washington DC, USA
Dr. Augusto M. Manalo: “Thank you, and good morning. On the management of gynecological cancers in developing countries, I would like to present the experience of the Philippines. In the Philippines, cancer of the cervix is still the most frequent gynecological malignancy; it far exceeds cancer of the ovary and cancer of the endometrium. If we consider all cancers affecting our women, it runs second exceeded only by cancer of the breast. If we consider all cancers affecting both sexes, it ranks fourth exceeded by cancer of the lungs, cancer of the breast, and cancer of the liver. In the 1998 Philippine Cancer Facts and Estimates, it was predicted that about 4,536 new cases of cancer of the cervix would be seen and about 2,204 deaths from this malignancy would occur. At the Philippine General Hospital, the country’s leading referral center for cancer, about 600 new cases are seen every year. The majority of these cases are in the late stages, stage II-B and above and this stage distribution is also observed in other major hospitals, and very few intraepithelial lesions are seen. These facts that have remained unchanged for many, many years speak very poorly about our past efforts of cervical cancer control. We have targeted perhaps less than 10% of our susceptible women. Sociocultural factors, economic factors, and other government priorities have been blamed for this and health resources limited as they are have been directed to control of communicable diseases, safe motherhood, and promotion of children’s health.
In the treatment, we follow the international guideline of radiotherapy for all stages. Since 1999, however, we have advised concomitant chemotherapy and radiotherapy following the NCI recommendation. The chemotherapeutic agent used is Cisplatin. For external radiation, depending upon the institution, we use either the colbalt-60 machine or the linear accelerator and for the intracavitary radiation, again, depending upon the institution, we make use of the low dose rate or the high dose rate. Cisplatin is given either as 50 mg every week or 100 mg every three weeks. For convenience of the patient, we usually give it at 100 mg every three weeks. We limit our radical hysterectomy and bilateral pelvic lymphadenectomy to stages I-B and II-A where the tumor diameter is equal to or less than 4 cm. With findings of deep cervical stromal invasion or tumor extension to the parametria, we give pelvic radiation. Then with findings of positive nodes, we give pelvic radiation and periaortic radiation, and with the finding of a tumor at the margin of vaginal resection, we give pelvic radiation and vaginal brachytherapy. With post-operative radiation, we also give chemotherapy if the patient can afford it. One of the problems that we have encountered in the treatment of cancer of the cervix is limited radiation facilities. There are only five government hospitals and eight private hospitals with functional radiotherapy units in the whole country.
We also encounter the problem of the high cost of chemotherapy; very few of our patients can afford the very expensive chemotherapeutic agents. We also encounter the problem of inadequate surgery. There are only fifty-three gynecologic oncologists in the country that can perform radical hysterectomy and bilateral pelvic lymphadenectomy. Many of these patients are operated upon by general obstetrician-gynecologists, and some just have a total hysterectomy. The referral system in our country is still far from ideal. For cancer of the endometrium, we have followed the 1988 FIGO recommendation of primary surgical approach and surgical pathological staging. Following peritoneal fluid cytology, exploration of the whole abdomen, total hysterectomy, bilateral salpingo-oophorectomy, and pelvic and periaortic lymph node assessment, we try to identify patients without any poor prognostic factor who will need no further treatment. We also try to identify patients with poor prognostic factors who will need pelvic radiation with or without vaginal radiation and with or without periaortic radiation. We also try to identify patients who will need chemotherapy and patients who will need hormone therapy. Patients who will need chemotherapy, particularly those who have unfavorable histologic types, patients who are poorly differentiated with poorly differentiated tumors, those with positive peritoneal cytology, and those with adnexal spread. Hormone therapy requires the determination of receptor levels, however, this is not very easily available in our country. If they are available, they are very expensive so that many times we have to use clinical and pathological findings that roughly reflect receptor levels, like the degree of histologic differentiation, the character of the non-neoplastic endometrium, the presence of hyperplasia, and the classic risk factors for endometrial cancer.
The hormones used are medroxyprogesterone acetate and megestrol acetate. In our hospital, we actually perform bilateral pelvic lymphadenectomy and sometimes also a periaortic lymphadenectomy. We have also de-emphasized fractional curettage in favor of endometrial biopsy and simple curettage for the very same reason that FIGO claims but the procedure is fraught with error, and that assessment of endocervical involvement is best done in the surgical specimen. However, we feel that we cannot completely avoid doing fractional curettage. Radiotherapy is not very easily accessible in many parts of our country, and we feel that certain cases of well-differentiated adenocarcinomas in young, good surgical risk patients with operatively known endocervical involvement can benefit from radical hysterectomy and bilateral pelvic lymphadenectomy. If we do not find any poor prognostic factor other than endocervical involvement then radiotherapy, inaccessible as it is, will not be necessary any more. Because we cannot completely do away with fractional curettage, we had to do something to minimize the errors inherent in the procedure. In a fairly recent study of the Philippine General Hospital, involving some 1,522 hysterectomy specimens, the depth of the endocervical canal which is important as this determines the depth at which the endocervical curette must be inserted, was found to be 2.5 cm and this depth was not affected by age, parity, menopausal status, and pelvic pathology. We have also found it necessary to advocate vigorous endocervical curettage, vigorous enough to include the underlying normal cervical tissue because we believe that the finding of malignancy in histologic continuity with normal cervical tissue is the only conclusive way of determining endocervical involvement.
There has recently been controversy regarding the benefits of radical hysterectomy and bilateral pelvic lymphadenectomy in stage II-A and, therefore, a possible modification of the fractional curettage would be endometrial biopsy, endocervical curettage, and transvaginal ultrasonography to be performed only while our adjacent facilities are not very adequate. Now as in many other countries our cancer of the ovary is often discovered late and patients are generally malnourished and anemic, and this limits the extent to whom cytoreductive surgery is performed. A major problem in the treatment is the high cost of chemotherapy, particularly, the chemotherapeutic agent that is being recommended for unsatisfactorily debulk tumors. The popular drug combinations used are cisplatin and cyclophosphamide, cisplatin and doxorubicin and cyclophosphamide, and paclitaxel and carboplatin, and for the germ cell tumors – vincristine and actinomycin-d and cyclophosphamide, and bleomycin and etoposide and cisplatin.
The second-look operation is very seldom done. First, it is very difficult to convince patients who have been told that they are clinically free of disease to undergo surgery just to find out if in indeed they have no evidence of disease. Secondly, because of the reports in the literature that a negative second look operation does not guarantee against future recurrence. And thirdly, because of a very disturbing thought that distress of surgery and anesthesia may cause dormant sequestered tumor cells to be activated. Interval or secondary debulking is practiced, however, we encounter the problem of choosing the second line chemotherapy. Survival figures - we have no meaningful survival figures because of very poor patient follow-up. For cancer of the ovary, for example, after one year the follow-up rate drops to less than 50%. This is the best that we can have regarding the three-year follow-up of cancer of the cervix. For stage I we have 68, II-A 56, II-B 45, stage III 38, and stage IV zero, and this is just a three-year survival rate. Now once in a while in the treatment of these malignancies, and I will say not only once in a while but frequently, we encounter the problem of persistent and recurrent disease. This is a very difficult problem and many times individualization becomes the rule. If the initial treatment is surgery we give radiotherapy, this time concomitant radiotherapy and chemotherapy. If the initial treatment is radiotherapy or concomitant radiotherapy and chemotherapy and if the disease is central, we try to perform surgery and the surgery can be either in the form of a total hysterectomy or a radical hysterectomy. If surgery cannot be performed, then we advise for whatever good it will do to the patient the newer chemotherapeutic agents like irinotecan or liposomal Taxol will be seen.
Now we also encounter the problem of very advanced disease, and I would like to say that palliative care in our country is still in its infancy. In spite of the World Health Organization guidelines, control of pain, for example, is still an aspect of treatment of which many of our physicians know very little about. There is still much hesitancy and self-imposed restriction in the use of strong opioids. Why, we do not know, perhaps, the reason is still fear of addiction. There are also organized multidisciplinary things to take care of the psychological needs and the spiritual needs of our terminally ill patients. Now in summary, the management of gynecological cancers in our country is undertaken by fifty-three gynecologic oncologists who are mainly located in the big cities. They are assisted to a very great extent by general obstetricians and gynecologists who every now and then will make blunders but who every now and then will also make very timely referrals. Our gynecologic oncologists are very much aware of what is current in the field but cannot effectively implement treatment because of sociocultural reasons, economic reasons, and government priorities that seem to be directed elsewhere. A major disadvantage in our country is our geography. The Philippines have 7,000 islands although some of these are not really inhabited, and many of these islands are very inaccessible to adequate medical care. Then, of course, we still have to overcome our poverty.