Neoadjuvant Chemo Linked to Above 95% OS in Squamous Cell Cervical Cancer

A review of patients with locally advanced bulky squamous cell carcinoma (SCC) of the uterine cervix who underwent chemoradiation followed by surgery with pelvic lymphadenectomy showed that the technique was associated with a 5-year overall survival (OS) of 95.7%.

At a median follow-up of 121 months (range 17-180), progression-free survival (PFS) was 86.7%.

Investigators with the department of obstetrics and gynecology at Saga University, Saga, Japan, sought to assess the efficacy of adjuvant surgery after concurrent chemoradiotherapy (CCRT) in patients with bulky SCC of the uterine cervix. Though the combination of chemotherapy, radiation, and surgery was associated with strong outcomes, the toxicity associated with this modality means that it may not be appropriate for widespread use.

“Adjuvant surgery after CCRT for bulky SCC of the uterine cervix seems to be extremely effective, especially for long-term survival. However, it became clear that this strategy combined 3 modalities including chemotherapy, radiotherapy, and surgery, which frequently caused severe long-lasting complications affecting the quality of life. Application of this strategy should be absolutely limited to only those cases with extremely poor responder of CCRT, after careful informed consent,” first author Yoshifumi Nakao, MD, and coinvestigators wrote.

Tumor size is one of the most important risk factors in the prognosis of uterine cervical cancer. Patients with stage IB or IIA and tumor size greater than 4 cm in diameter generally have a poorer prognosis, with a 5-year OS of 64% and disease-free survival of 67%.

Results from previous meta-analyses exploring treatment for locally advanced uterine cervical cancer have shown that CCRT is associated with superior rates of OS and PFS rates compared with radiotherapy alone, and is recognized as the standard treatment. However, such treatment remains suboptimal, and 40% to 50% of patients are left with histopathologic residual tumor. These findings support the hypothesis that an adjuvant surgical resection could improve the local control and the overall prognosis, but the benefits of adjuvant surgery remain controversial.

To evaluate CCRT, investigators recruited patients who were admitted to Saga University Hospital with stages IB2 to IIIB bulky cervical cancer from August 2000 to February 2006 (N = 23). Eligible patients had biopsy-proven SCC of the uterine cervix, no radiological evidence of distant metastasis except para-aortic lymph nodes, were 75 years or younger, ECOG performance status ≤2, adequate bone marrow function, adequate renal function, and normal liver function.

All patients completed the scheduled radiotherapy. No patient required chemotherapeutic delay due to acute toxicity. The average duration from last brachytherapy to surgery was 32.6 days. All patients underwent hysterectomy, pelvic lymphadenectomy, and lower abdominal para-aortic lymph node sampling, and all were evaluated for radiological and pathological response.

All patients showed a response upon radiological examination, including 17 (73.9%) who had complete response (CR).

Twelve patients (52.2%) had a pathological CR (pCR) of the uterine cervical tumor, and 11 (47.8%) showed partial pathological response. All pCR cases also showed CR in preoperative radiological examination.

Fifteen patients (65.2%) showed swollen pelvic lymph nodes in radiological screening before CCRT, 86.7% of whom had multiple anatomical sites simultaneously. Among these 15 patients, 8 (53.3%) had CR and 5 (33.3%) had a partial response.

On pathological review of the resected nodes, only 1 lesion contained viable cancer cells among the radiological CR cases. Investigators did not find any para-aortic lymph node metastasis in resected nodes.

There were no treatment-related deaths in the study, though 1 patient died of recurrence and 2 died of unknown reasons after more than 100 months. Seven events in 4 patients led to the development of postoperative fistula formation requiring a rescue surgery. Three patients (13.0%) developed distant metastases, 1 of whom showed local recurrence later.

Nakao Y, Hashiguchi M, Nishiyama S, et al. Preoperative chemoradiotherapy in locally advanced bulky squamous cell carcinoma of the uterine cervix [published online August 3, 2017]. Int J Gynecol Cancer. doi: 10.1097/IGC.0000000000001094.