Although gynecologic cancers account for only 10% of all new cancer cases in women, these cancers account for 20% of all female cancer survivors. Improvements in cancer care have resulted in almost 10 million cancer survivors, and this number is expected to grow. Therefore, determining the most cost-effective clinical surveillance for detection of recurrence is critical. Unfortunately, there has been a paucity of research in what are the most cost-effective strategies for surveillance once patients have achieved a complete response. Currently, most recommendations are based on retrospective studies and expert opinion. Taking a thorough history, performing a thorough examination, and educating cancer survivors about concerning symptoms is the most effective method for the detection of most gynecologic cancer recurrences. There is very little evidence that routine cytologic procedures or imaging improves the ability to detect gynecologic cancer recurrence at a stage that will impact cure or response rates to salvage therapy. This article will review the most recent data on surveillance for gynecologic cancer recurrence in women who have had a complete response to primary cancer therapy.
In 2010, gynecologic malignancies were expected to afflict approximately 80,000 women within the United States. Advances within the field of gynecologic oncology have resulted in long-term survivals and a high rate of survivors. Because long-term survival is becoming more common in this patient population, insights into cancer surveillance and detection of recurrence and addressing side-effects from treatment are of utmost importance.
Currently, posttreatment guidelines call for frequent visits immediately after treatment, followed by increasing intervals over time. Typically, after the first 2-3 years, patients are transitioned back to their primary care providers. However, primary care physicians may not be comfortable with guidelines or surveillance for each specific cancer type. This is in part due to a lack of training and in part to unclear expectations for the primary care provider by the oncologist. As survivorship continues to grow, coordination of care between gynecologic oncologists, primary care providers, other healthcare providers (such as radiation oncologists), and patients ideally will allow for compliance with cancer follow-up care and routine health maintenance. The provision of a clear understanding of recommendations and responsibilities of appropriate surveillance will reduce unnecessary tests and ultimately result in cost savings.
The role of surveillance is to provide clinical and cost-effective practices that detect recurrence and impact survival outcomes. Acceptance of surveillance should be considered if there is utility of treatment for recurrence and decreased morbidity from both monitoring for disease recurrence and treatment. One should also consider the costs and the use of resources for conducting these tests. Last, patients should be counseled on the benefits and pitfalls of disease monitoring, which should include the psychologic impact of surveillance programs. Unfortunately, most studies across all cancer sites are based predominantly on retrospective studies and provide limited insight into the true benefit of recommended guidelines for posttreatment surveillance. There is a real need for prospective studies to establish the most cost-effective methods for the detection of recurrent disease. In addition, surveillance tests should be directed at detecting recurrences that are amenable to curative or significant palliative treatment. Therefore, the primary objective of this review is to provide the most recent data on surveillance for cancer recurrence in women who have had a complete response to primary cancer therapy for gynecologic malignancies. Additionally, we have included routine health screening guidelines to allow for enhanced communication between oncologists and primary care providers.
Endometrial cancer
Endometrial cancer is the most common gynecologic cancer and the fourth most common cancer in women. Yearly, there are approximately 44,000 new endometrial cancer diagnoses and 8000 deaths in the United States. Commonly, patients experience symptoms such as abnormal or postmenopausal bleeding, which warrant further investigation with ultrasound scanning and/or endometrial sampling. The combination of symptoms and diagnostic testing results in 83% of patients being diagnosed in the early stages of the disease. As a result of localized disease, 5-year survival rates exceed 95% for stage I and approach 83% overall. However, recurrence rates for patients with early-stage disease range from 2–15% and reach as high as 50% in advanced stages or in patients with aggressive histologic condition. Many local recurrences from endometrial cancer are curable; therefore, the determination of the ideal time interval and diagnostic tools for surveillance of recurrent endometrial cancer that can impact survival outcomes is critical.
Typically, surveillance guidelines are more intensive the first few years after diagnosis because many studies have shown that most (70-100%) recurrences occur within 3 years after primary treatment. Current guidelines of the National Comprehensive Cancer Network (NCCN) and the American Congress of Obstetricians and Gynecologists recommend physical examination every 3-6 months for 2 years, then every 6 months or annually. Further evaluation with vaginal cytologic evidence is recommended every 6 months for 2 years and annually thereafter. To date, there are no prospective studies that have evaluated the role of surveillance in endometrial cancer follow-up evaluation. Based on recommended guidelines and institutional practices, retrospective research and literature reviews comprise the best evidence that is available.
The most consistently used method for surveillance is the physical examination. This alone accounts for a high rate of detection that ranges from 35-68% of cases. Even more striking is that the combination of physical examination and symptoms has resulted in rates of detection that exceed 80%. In a recent literature review, Sartori et al report that only physical examination has shown utility in the detection of endometrial cancer recurrence. Therefore, physical examination, which includes a thorough speculum, pelvic, and rectovaginal examination, should be conducted during each follow-up assessment.
The role of surveillance is based on the concept that detection of recurrences in the asymptomatic stage results in better therapeutic options and outcomes. Interestingly, even in spite of intensive surveillance, many recurrences are detected based on the presence of symptoms, which occurs in 41-83% of patients. A common symptom, vaginal bleeding, is indicative of a local recurrence that is often curable if it is an isolated site of disease. However, other common symptoms include abdominal and/or pelvic pain, lethargy, and weight loss. Even in the face of monitoring for recurrence, patients who experience a distant recurrence are symptomatic in 70% of cases, such as coughing or headaches. Therefore, patient education about the signs and symptoms is a critical component of posttreatment care and may lead to the detection of recurrent disease.
Survival outcomes have been evaluated on the basis of the presence or absence of symptoms at the time of recurrence. In a report by Sartori et al, 52% of patients were diagnosed with recurrence after they had symptoms; these patients had a median postrecurrence survival of 7 months. This was significantly less than the 20-month survival that patients experienced if they were diagnosed with recurrence in an asymptomatic state that was based on examination or imaging. Several other series have evaluated the role of routine surveillance for the follow up evaluation of patients with stage I endometrial cancer and reported no difference in survival based on the presence or absence of symptoms. Of note, even patients who had symptoms were undergoing the recommended follow-up evaluations, which provided an argument against the use of routine surveillance. Although all of these studies were retrospective, they reiterate the importance of prospective trials to determine the true role and regimen for surveillance.
Because most recurrences occur at the vaginal cuff, the use of cytologic evaluation has been advocated. However, many gynecologic oncologists challenge this recommendation. Rates of recurrence detection on vaginal cytologic evidence range from 0–6.8%, even in asymptomatic patients. Although Berchuck et al and Owen and Duncan report that cytologic evaluation detected 25% of all recurrences and that cytologic evaluation alone detected only 3 of the 44 (7%) recurrences. Furthermore, in addition to a low yield of detection, Agboola et al reported that the use of vaginal cytologic evaluation at each visit resulted in a cost of $27,000 per case detected. Because most recurrences at the vaginal cuff can be found on examination, vaginal cytologic evaluation adds only significant healthcare costs without added benefit.
Similarly to ovarian cancer, the use of cancer antigen 125 (CA125) level has been investigated as a marker for recurrence. In asymptomatic patients with endometrial cancer, the use of CA125 levels accounted for 15% of detections. Rose et al reported that CA125 levels were elevated in more than one-half of the patients with advanced stage and/or high-grade histologic evidence and that of these patients most had an elevated pretreatment level. However, one must be aware of elevated CA125 levels because of other conditions or even previous radiotherapy. In addition, the role of CA125 levels for the detection of recurrence was negligible in patients with low-risk disease. At present, the use of CA125 levels should not be used routinely in patients with endometrial cancer but may be appropriate in select patients with advanced disease, serous histologic condition, or a CA125 level that is elevated before treatment.
The use of radiographic imaging has been suggested for the detection of recurrent disease. Because of low costs, chest radiographs have been advocated for the detection of asymptomatic recurrences, often on a semiannual or annual basis. The rate of detection for asymptomatic chest recurrences that are found on chest radiographs ranges from 0–20%. In another series, chest radiograph detected 7 asymptomatic pulmonary recurrences and accounted for 0.34% of all chest radiographs that were performed for surveillance, which indicates low utility for this tool. Although reports of isolated pulmonary recurrences, albeit rare, may be amenable to therapies that allow for long-term survival outcomes, the routine use of chest radiographs is not recommended.
In further evaluation of radiographic imaging for endometrial cancer surveillance, Fung Kee Fung et al conducted a review of the literature and found that only 5-21% of asymptomatic recurrences were found by computed tomography (CT) scans. Other studies have agreed that the role of CT scanning for asymptomatic patients is not warranted, because survival of patients with disease that is detected on CT scan, compared with clinical examination, did not differ significantly. To increase the detection of local recurrence, the use of pelvic ultrasound scans has also been reported. Although detection rates for local recurrence range from 4–31%, many of these recurrences were also detected on other diagnostic methods, which included physical examination. Therefore, the use of routine pelvic ultrasound and CT scanning is not advocated; however, these modalities may play a role in the evaluation of patients with symptoms, because the rates of detection approach 50% of cases.
More recently, attention has been focused on positron emission test (PET) ± CT scans for endometrial cancer recurrence. Park et al reported 100% sensitivity and 83% specificity when PET-CT scanning was used for suspected recurrence and 100% diagnostic accuracy in 64 asymptomatic patients. However, its use for routine screening has not been well studied, and larger prospective studies will determine whether PET/CT will have a role in endometrial cancer surveillance. In addition, the high cost of PET/CT may limit its use in routine surveillance ( Table 1 ).
| Method of detection | Type of cancer, % | ||
|---|---|---|---|
| Endometrial | Ovarian | Cervical | |
| Symptoms | 41-83 | — | 46-95 |
| Physical examination | 35-68 | 15-78 | 29-75 |
| Cytologic evidence | 0-7 | — | 0-17 |
| Chest radiograph | 0-20 | — | 20-47 |
| Cancer antigen 125 level | 15 | 62-74 | — |
| Computed tomography scan | 0-20 | 40-93 | 0-45 a |
| Positron emission test–computed tomography scan | 100 a | 45-100 | 86 |
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