Patients w/ abnormal Pap smear are referred for colonoscopy to screen for presence of cervical cancer.
Colposcopic exam should include inspection of the transformation zone, definition of the extent of the lesion & biopsy of the most abnormal area for tissue diagnosis.
The earliest stages of cervical carcinoma are generally asymptomatic.
Watery vaginal discharge & postcoital bleeding or intermittent spotting may be present & are usually unrecognized by the patient.

Treatment of metastatic cervical cancer with chemotherapy and targeted therapy

Dr. Amy Chang
Specialist in Clinical Oncology
Hong Kong

Presentation and management
A 40-year-old Chinese female presented to the clinic in March 2014 after an episode of postcoital bleeding. She had been undergoing annual cervical smear examinations, with no abnormal findings noted. Her past medical history was unremarkable. Physical examination revealed a 4 cm necrotic mass at the cervix, which was assessed on biopsy to be an invasive non-keratinizing squamous cell carcinoma. MRI did not reveal any metastasis or lymph node involvement, and the patient’s disease was classified as stage IB.

In June 2014, the patient underwent Wertheim’s hysterectomy, bilateral salpingo-oophorectomy and bilateral pelvic lymphadenectomy. Histopathological examination of the tumour revealed a large-cell non-keratinizing squamous cell carcinoma measuring 7 cm in diameter with clear resection margins. None of the 26 lymph nodes resected were positive for malignancy. There was note of deep stromal invasion but no lymphovascular or perineural permeation. As the tumour was larger than the expected diameter of 4 cm, the patient’s disease stage was reclassified to stage IB2.

The patient received postoperative whole pelvis radiotherapy with a dose of 50 Gy given in 25 fractions over a period of 5 weeks. The treatment was completed in September 2014. Follow-up visits to the clinical oncology service and the gynaecology service were scheduled every 3 weeks. No evidence of relapse was noted during these visits until April 2015, when the patient began to experience a mild, dry cough, and surveillance CT scan revealed multiple lung metastases. During this period, her Eastern Cooperative Oncology Group performance status was 1. Follow-up PET scan showed multiple lung and mediastinal lymph node involvement. The metastases numbered greater than 8 and were considered inoperable.

Palliative chemotherapy was initiated and consisted of Paclitaxel 175 mg/m2 and Cisplatin 50 mg/m2, together with Bevacizumab at a dose of 15 mg/kg. Therapy was administered every 3 weeks, to complete a total of six cycles. An improvement in her cough was noted after the first cycle. The treatment was well tolerated, with only mild grade 1 peripheral neuropathy noted. A progress CT scan in August 2015 after five cycles of chemotherapy showed a reduction in size of the lung metastases. (Figure) The patient has completed the planned six cycles of palliative chemotherapy and will be maintained on Bevacizumab 15 mg/kg every 3 weeks until disease progression.

Figure. CT scan after five cycles of Paclitaxel, Cisplatin and Bevacizumab showing reduction in size of lung metastases (B) compared with baseline (A)
DRC cervical cancer - treatment case 1 fig 1a

DRC cervical cancer - treatment case 1 fig 1b

Patients with metastatic cervical cancer have limited survival.1 The presence of multiple metastatic lesions makes these cases inoperable.2 Thus, the remaining treatment option in this setting is chemotherapy, usually with a platinum-based regimen, such as Cisplatin or Carboplatin, plus Paclitaxel. For patients who cannot tolerate platinum-based chemotherapy, Topotecan may be given in place of Cisplatin.2

Bevacizumab, a humanized anti-VEGF antibody, has demonstrated activity as monotherapy in previously treated patients with recurrent cervical cancer.3 A recent study evaluated the efficacy of Bevacizumab added to standard Cisplatin or Topotecan plus Paclitaxel chemotherapy in patients with metastatic, persistent or recurrent ovarian cancer. A total of 452 patients were randomized to receive either chemotherapy alone or chemotherapy plus Bevacizumab. Median overall survival was significantly prolonged in patients who received Bevacizumab in addition to standard chemotherapy compared with patients who received chemotherapy alone (17 vs 13.3 months; hazard ratio, 0.71; p=0.004) – a survival benefit of 3.7 months.3 Patients who received Bevacizumab in addition to chemotherapy also had significantly higher response rates (48 vs 36 percent; p=0.008). Notably, however, there was a higher incidence of hypertension and thromboembolic events in the group receiving Bevacizumab.

Since both Cisplatin and Paclitaxel can cause peripheral neuropathy, the emergence of this side effect may be a limiting factor in the treatment of patients receiving these agents. However, our patient tolerated the treatment well, experiencing only grade 1 peripheral neuropathy.

In summary, this case illustrates the successful use of chemotherapy combined with targeted therapy in the management of metastatic cervical cancer. In our patient, the treatment has resulted in a fairly long duration of disease control and was well tolerated.

1. American Cancer Society. Cervical cancer: survival rates by stage: http://www.cancer.org/Cancer/CervicalCancer/DetailedGuide/cervical-cancer-survival.
2. J Clin Oncol 2007;25:2966-2974.
3. N Engl J Med 2014;370:734-743.

This special report is made possible through an unrestricted educational grant from the industry and first appeared in MIMS Oncology.
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