Location of recurrent asymptomatic ovarian cancer through endoscopic ultrasound.

Ovarian cancer is frequent and recurrence happens in about 75% of patients. As it presents high rates of relapse, the exams for this diagnosis are widely discussed. Beside this, there have been discussions about benefits for early anatomic diagnosis and whether endoscopic ultrasound (EUS) can be used to track the relapse of the disease. We present a case, in which anatomic location and histological definition of an asymptomatic recurrence of the ovarian cancer was misdiagnosed with conventional methods, but was possible through EUS.

INTRODUCTION

Ovarian cancer is the fifth largest cause of death related to cancers and it is responsible for more than half of all deaths related to gynecological cancer.[1] The diagnosis is usually carried out in its advanced stage and even though it responds well to primary treatment, achieving clinical remission in 50% of cases, a complete cure is rare and recurrence happens in three out of four patients.[2]

The patients who present complete clinical remission are monitored by physical exams, cancer antigen-125 (CA-125) serum dosage and radiological exams, such as, computed tomography (CT) or tomography associated with positron emissions (PET-CT).[34]

CASE REPORT

Sixty-three-year-old nulliparous patient, presenting with second relapse of epithelial ovarian cancer diagnosed by the increasing level of serum tumor markers with negative radiological studies.

The patient was diagnosed with epithelial ovarian cancer 7 years ago, when she underwent surgical resection (Wertheim-Meigs surgery), associated with adjuvant chemotherapy using cisplatin/paclitaxel (CP), presenting complete clinical remission, with the absence of signs and symptoms, normal levels of CA-125 and negative PET-CT.

Five years ago, she developed the peritoneal relapse, and was treated with neoadjuvant chemotherapy with CP, peritonectomy with hyperthermic intraperitoneal chemotherapy, followed by adjuvant chemotherapy with the same drugs, once again, presenting complete clinical remission.

One year ago, she presented with an increase in CA-125 serum level for 3 months. On this occasion, she had a PET-CT, which showed the densification of peritoneal fat in the lower abdomen with fibro-cicatricial characteristics, unchanged in comparison to the previous examinations, besides showing heterogeneous parietal gastric thickening associated with the densification of the surrounding fat planes. There was no evidence of abnormal contrast enhancement [Figure 1]. The upper digestive echo-endoscopy showed unspecific parietal gastric thickening, a small slide with perihepatic ascites and three oval-shaped hypo-echogenic and heterogeneous formations with septations and anechoic content, measuring around 10 mm [Figure 2], located between the hepatic hilum and the peripancreatic cephalic region that were punctured with 22-gauge needle.

Figure 1

Positron emission tomography-computed tomography aspect

Figure 2

Echo-endoscopic aspect

Histologic study confirmed the diagnosis of metastatic serous cystadenocarcinoma, the immunohistochemical study indicated the gynecological tract as the primary site [Figure 3]. It was not possible to determine accurately whether the injury observed in endoscopic ultrasound (EUS) were tumor implants or lymph node recurrence.

Figure 3

Histologic and immunohistochemical (WT-1, cancer antigen-125 and estrogen receptor antibodies) aspect

After the diagnosis of a second relapse, the patient underwent chemotherapy with CP, but did not show significant improvement. Due to resistance to platinum-based chemotherapy, she switched to bevacizumab and liposomal doxorubicin therapy, with good response, presenting, once again, complete clinical remission. Nowadays, the patient's clinical exams are normal. CA-125 serum levels been normal and the upper digestive echo-endoscopy confirmed regression of the previously identified lesions.

DISCUSSION

In the English literature, there are seven cases where EUS assisted in the diagnosis of recurrent ovarian tumor. In all cases, the lesions had been detected previously by another method [Table 1]. In the current report, the anatomic diagnosis was exclusively performed by EUS, and all other imaging studies were normal.

Table 1

Case reports with the lesions detected previously by another method

In about 70% of patients, increased serum levels of CA-125 may be the first sign of relapse, preceding clinical relapse with anatomical localization by conventional methods (CT and PET-CT) in an average period of 4 months.[12] In the current report, the recurrence could be diagnosed by EUS in 3 months. The authors believe that the recurrence pattern justifies the fact that the diagnosis was done only through EUS, which presents a higher sensitivity for lesions with minor dimension. Epithelial ovarian cancer, in a significant proportion, shows relapse through nodular and diffuse micro-lesions, in contrast to other solid tumors that present with masses with larger dimensions.[2]

There have been a lot of discussions about the real impact of early anatomic diagnosis of tumor relapse. Cannistra affirm that there is no evidence of benefit for starting early chemotherapy in patients that present only positive tumor markers. For these patients, hormonal therapy, using tamoxifen or aromatase inhibitor, is recommended, while chemotherapy and cytoreductive surgery (CRS) is used as a second plan for patients whose relapses have been confirmed through imaging methods.[3] Fleming et al. affirms that the levels of CA-125 can help recruit people to secondary CRS, and a shorter period between the increase in CA-125 level and surgical intervention correlate to a higher occurrence of ideal resection, increasing overall survival from 23 months to 47 months.[13] In more recent study, Wang et al. also showed an increase in overall survival with early diagnosis.[2] Even with some divergences between authors, early diagnosis has an impact on how the cases are handled, whether because it influences the type of therapy that will be decided on or because it increases overall survival.

In 2006, Herman published characteristics of a good screening examination: one that can detect a high proportion of disease in its preclinical state, safe to administer, at a reasonable cost, provide improved health results and be widely available.[14] Due to anatomic limitations, the upper digestive EUS does not give access to all possible relapse sites and certainly would not detect, in high proportions, a recurrence of ovarian cancer, rating it as unfit in some of the established criteria.

After treating the case and literature review, we believe that EUS brought benefits to the patient. EUS shouldn‐t be recommended as a screening procedure for mass in recurrence epithelial ovarian cancer, but maybe it will have a place in the screening for selective cases with increasing CA-125 without the exact anatomic location by current standard methods.