FOLLOW-UP OF PATIENTS WITH EPITHELIAL OVARIAN, TUBAL AND PRIMARY PERITONEAL CANCER
Tally Levy, MD, MHA

Division of Gynecologic Oncology, Wolfson Medical Center, Holon and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv Israel
Epithelial ovarian cancer (EOC) is the leading cause of death among gynecologic malignancies. Most patients have chemosensitive disease that responds to initial platinum/taxane chemotherapy with high response rates. However, in those diagnosed with advanced disease, recurrence rates are higher than 80% (1,2). Recurrent disease is inevitably fatal, with death usually occurring within 18–24 months. Treatment of recurrent ovarian cancer remains a challenge despite advances in surgical and chemotherapeutic options. Treatment for recurrent disease is usually not curative and intends to be palliative. Current practice involves intensive long-term surveillance of women for recurrence by physical and gynecologic exams, serum biomarkers, and imaging. The rationale for surveillance of ovarian cancer patients is based on the premise that prompt detection and treatment of an asymptomatic patient will result in significant improvements in quality of life, palliation of symptoms, and potentially even prolonged survival (3-5).
The optimal surveillance strategy for women in first clinical remission has been poorly studied. The National Comprehensive Care Network (NCCN) guidelines for post-treatment surveillance of women with ovarian cancer recommend office visits every 2–4 months for the first two years and then every 3–6 months for the following three years. Each visit includes a full interval history and a physical exam aimed at detecting recurrence (6). Patients are screened for symptoms such as bloating, increased urinary frequency, early satiety, increased abdominal girth, and abdominal/pelvic pain (7). In addition, a physical exam, including a pelvic exam and rectovaginal exam, has been shown to be useful in detecting abnormalities (7). The NCCN also recommends obtaining a CA-125 level at each visit and imaging as clinically indicated (6).
In June 2011, SGO published recommendations for post-treatment surveillance in women who had achieved a full response to adjuvant therapy. These evidence-based guidelines are generally congruent with the NCCN guidelines with an emphasis on symptom assessment and the physical exam. According to SGO recommendations, the role of CA125 should be reviewed with patients and surveillance with this marker is optional (8).
CA-125 levels are elevated in approximately 80% of individuals with EOC, and these elevated levels correlate with disease progression (9). In fact, CA-125 may also be elevated several months prior to symptomatic recurrence (10). A multicenter study by Rustin et al (11) from the United Kingdom, however, showed that treatment for recurrences based solely on elevations in CA-125 did not increase overall survival (OS). On the other hand, several retrospective studies show that post-recurrence
survival is significantly greater in asymptomatic patients (12). Moreover, if secondary cytoreductive surgery (SCS) was done, optimal residual disease (≤ 5 mm) was more often achieved in asymptomatic patients (12).Fleming et al (13) concluded that serial CA-125 surveillance for early detection of recurrence may increase rates of optimal SCS and potentially influence OS.
Criticism of the Rustin trial includes several points: Although prospective in nature, treatment type, number of cycles, and number of treatments varied between the early and delayed groups. By design, the platinum-free interval was imbalanced in the study because some patients started treatment early and others were delayed. Contemporary therapies were not available to most of the trial participants because of the chronological length of the trial. A treatment-free interval exceeding 12 months was found in 45% of the randomized patients and they were therefore potential surgical candidates for SCS, but only 7% received surgical intervention. Thus, it seems that the question whether the diagnosis and treatment of early recurrence affects outcome is still not completely settled.
Furthermore, Levy et al (14) has shown that a rise of CA-125 within the normal range may predict recurrence. The pattern of ascent of serum CA125 levels to above the normal range in patients in complete clinical remission is of prognostic value. Patients with a gradual CA125 rise to above the normal range have a significantly better progression-free survival (PFS) and OS than those with an abrupt rise (15).
In conclusion, there is no evidence that any of the surveillance modalities will impact survival versus waiting for the presentation of symptoms and initiating treatment at that point in time. However, for many patients the follow-up visit presents an opportunity for medical reassurance. The psychological benefit to follow up is important, and providing these services in a cost-effective manner is paramount.
Interventions to proactively reduce patient stress, anxiety and/or depression may be an appropriate consideration.
The approach to post-treatment surveillance should be individualized taking into account the clinical benefit of the second-line therapy, costs, morbidity and mortality of the surveillance methods, available treatment options and, lastly, patient preference.

References
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