Neoadjuvant chemotherapy for patients with international federation of gynecology and obstetrics stages IB3 and IIA2 cervical cancer: a multicenter prospective trial

Abstract

Background Preoperative neoadjuvant chemotherapy (NACT) has been widely used in developing countries for the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB3 and IIA2 cervical cancer. However, the effectiveness of NACT and treatment options for NACT-insensitive patients have been concerning. This study will assess prognostic differences between NACT and primary surgery treatment (PST), determine factors associated with prognosis, and explore better adjuvant treatment modalities for NACT-insensitive patients. Methods This study analyzed clinical characteristics, pathological characteristics, treatment options, and follow-up information of 774 patients with FIGO stages IB3 and IIA2 cervical cancer from 28 centers from January 2016 to October 2019 who participated in a multicenter, prospective, randomized controlled trial. Results For patients undergoing NACT, the 5-year OS and PFS rate was 85.8 and 80.5% respectively. They were similar in the PST group. There was no significant difference in OS and PFS between clinical response (CR)/partial response (PR) groups and stable disease (SD)/progressive disease (PD) groups. Apart from deep cervical invasion (p = 0.046) affecting OS for patients undergoing NACT, no other clinical and pathological factors were associated with OS. 97.8% of NACT-insensitive patients opted for surgery. If these patients did not have intermediate- or high-risk factors, whether they had undergone postoperative adjuvant therapy was irrelevant to their prognosis, whereas for patients with intermediate- or high-risk factors, adjuvant chemotherapy resulted in better PFS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.019) and OS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.002). Conclusions NACT could be a choice for patients with FIGO stages IB3 and IIA2 cervical cancer. The main risk factor influencing prognosis in the NACT group is deep cervical invasion. After systematic treatment, insensitivity to NACT does not indicate a poorer prognosis. For NACT-insensitive patients, Chinese prefer surgery. Postoperative adjuvant therapy in patients with no intermediate- or high-risk factors does not improve prognosis, and chemotherapy in patients with intermediate- and high-risk factors is more effective than radiation therapy and other treatments. Trial registration The study was prospectively registered on ClinicalTrials.gov (NCT03308591); date of registration: 12/10/2017.

The prognostic value of radiological and pathological lymph node status in patients with cervical cancer who underwent neoadjuvant chemotherapy and followed hysterectomy

“…It is believed that patients who respond to NACT will benefit from this treatment 16 and studies have been conducted to predict responders in order to obtain survival benefits 17 . However, both our present study and a randomized clinical trial showed that response to NACT does not necessarily mean favorable survival outcomes 15 . The inconsistent correlation between clinical response to NACT and long-term survival implies that future studies should focus on identifying more robust prognostic factors, such as positive lymph node and LVSI after NACT, which were identified as independent risk factors for PFS and OS in our study.…”

Promising predictive molecular biomarkers for cervical cancer (Review)

“…These results suggest that protein levels of HIF-1α and VEGF-A may guide the selection of PCRT and NACT in patients because the reduction is associated with a higher probability of improved clinical responses. However, the predictive value of these markers seems to be limited to LACC because higher protein levels in patients with early-stage cancer correlated with a negative response to treatment with NACT ( 57 , 58 ).…”

Efficacy Analysis of Neoadjuvant versus Adjuvant Cisplatin-Paclitaxel Regimens for Initial Treatment of FIGO Stages IB3 and IIA2 Cervical Cancer

“…For non-metastatic cervical cancer, excluding International Federation of Gynecology and Obstetrics (FIGO) stages IA, IB1, IB2, and IIA1 cancers, concurrent platinum-based chemoradiation is recommended by the National Comprehensive Cancer Network (NCCN) guidelines [ 4 ]. However, clinical applications of these guidelines are limited because of the unavailability of radiotherapy facilities in China [ 5 ]. Concurrent platinum-based chemoradiation has significant adverse effects on reproductive organs during clinical management of cervical cancer [ 6 ], for example, vaginal injuries, ovarian failure, damage to endocrine function, pelvic tissue degeneration, and impaired sexual lifestyle [ 7 ].…”

“…Women who received concurrent platinum-based chemoradiation therapies are mostly unable to receive surgical resections because of severe pelvic tissue injuries. Therefore, gynecologists and oncologists want to improve current surgical practices for cervical cancers [ 5 ].…”

“…In women with cervical cancer stage IB3 (larger than 4 cm) and IIA2 (spread from the cervix to the upper two-thirds of the vagina), radical surgery is preferred. However, huge cancerous lesions are difficult to handle with only surgery [ 5 ]. In many parts of the world, especially in China, neoadjuvant concurrent platinum-based chemotherapy is a more accepted approach for stage IB3 and IIA2 cervical cancers to overcome the errors of radical surgeries [ 5 ].…”