National Comprehensive Cancer Network (NCCN) clinical practice guidelines for cervical cancer have recommended cisplatin-based CCRT as standard treatment for LACC [12] after five large-sample randomized controlled trials conducted by Gynecologic Oncology Group (GOG), Radiation Therapy Oncology Group (RTOG), and Southwest Oncology Group (SWOG) in the United States reported that concurrent radiotherapy could improve survival in cervical cancer [13]. However, many patients have residual tumors after treatment, leading to tumor progression or death.

To enhance the therapeutic effect and prognosis of cervical cancer, a variety of novel treatment strategies are actively being explored. The development of molecular targeted therapies has opened up new avenues. The GOG 240 Phase III clinical trial combined bevacizumab with chemotherapy for Stage IVB/recurrent/refractory cervical cancer patients, significantly improving their OS rate [14]. And based on this study, the Food and Drug Administration (FDA) approved bevacizumab for the first-line treatment of recalcitrant/recurrent/metastatic cervical cancer. In the RTOG 0417 phase II trial [15], bevacizumab combined with chemoradiotherapy was applied to stage IB to IIIB cervical cancer patients. The 3-year OS and disease-free survival (DFS) were 81.3% and 68.7%, respectively, while the incidence of grade 3 and 4 adverse events was 26.5% and 10.2%, respectively. However, since this treatment did not demonstrate superiority over historical controls with standard cisplatin chemoradiotherapy, further investigation with bevacizumab was not pursued. Bevacizumab increased the incidence of AEs such as hypertension, thrombosis, and gastrointestinal fistula while improving its efficacy [16], and its use has been greatly limited as drug resistance has developed. Immune checkpoint inhibitors are currently a hot spot of research in various oncology therapies. PD-1/PD-L1 inhibitors have shown remarkable efficacy in treating recurrent/metastatic cervical cancer [17, 18], and the FDA has approved pembrolizumab and nivolumab for treating recurrent/metastatic cervical cancer. Regarding immunotherapy for LACC, the CALLA Phase III clinical trial combined durvalumab or placebo with concurrent chemoradiotherapy in treating LACC patients [19], however, the results indicated that durvalumab combined with CCRT failed to improve the PFS of LACC patients. The KEYNOTE-A18 Phase III trial results suggested that combining immunotherapy with CCRT might achieve synergistic effects in patients with locally advanced cervical cancer. While targeted therapy and immunotherapy remain limited in their application for LACC, cytotoxic chemotherapy remains indispensable in the treatment of LACC [20].

Petrelli et al. [21] conducted a meta-analysis of 1500 patients, demonstrating that the combination of CCRT with a cisplatin-based dual agent significantly improved the OS (P = 0.0002, OR 0.65, 95%CI 0.51–0.81) and PFS (P = 0.006, OR 0.71, 95% CI 0.55–0.91) compared to weekly cisplatin single-agent CCRT. Similarly, another meta-analysis published by Ma et al. [22] showed that CCRT with a platinum-based doublet significantly improved OS (P = 0.01, HR 0.75, 95% CI 0.60–0.94) and PFS (P = 0.01, HR 0.78, 95% CI 0.65–0.94) compared with CCRT combined with cisplatin monotherapy. Consistent with past research, the combination of paclitaxel and platinum is often the favored chemotherapy regimen for treating LACC considering its impact on ORR and PFS [8]. However, the traditional formulation of paclitaxel is associated with reduced patient adherence due to its high frequency of AEs, such as myelosuppression and allergic reactions, thereby impacting overall treatment outcomes [23], and in this study, two patients in the TP group discontinued concurrent chemotherapy due to AEs of chemotherapy. Nab-paclitaxel, a 130 nano-meter albumin-bound paclitaxel complex, binds to specific receptors on the surface of tumor vascular endothelial cells, facilitating the uptake of paclitaxel into tumor cells via albumin-mediated endocytosis. It increases the concentration of paclitaxel in the tumor stroma, aggregates more anti-tumor drugs to the lesion, and ultimately enhances treatment outcomes. Furthermore, the absence of the requirement for co-solvents and desensitization pretreatment renders nab-paclitaxel more convenient and safer to administer [24].

Our study used nab-paclitaxel in CCRT to compare the efficacy and safety of chemotherapy regimens of single-agent cisplatin, paclitaxel combined with cisplatin, and nab-paclitaxel combined with cisplatin concurrent radiotherapy for LACC. The results showed differences in OS (P = 0.041, HR 0.527, 95%CI 0.314–0.884) and PFS (P = 0.003, HR 0.517, 95%CI 0.343–0.779) rates among the three groups. The 2-year OS rate was higher in patients in the nPP group than in the DDP group (92.2% vs. 78.1, P = 0.012 < 0.017, HR 0.525, 95% CI 0.307–0.899). However, there was no significant difference in the 2-year OS rate between the TP group and the DDP group (85.4 vs. 78.1%, P = 0.237), which may be related to the short follow-up time. An extended follow-up duration may be able to reveal a statistically discernible disparity in OS rates between the two groups. The 2-year PFS rate was higher in both the TP and nPP groups than in the DDP group (78.0% vs. 59.4%, P = 0.048; 88.2% vs. 59.4%, P = 0.001), and multiple comparisons suggested that the 2-year PFS rate was significantly higher in the nPP group compared with the TP group (P = 0.001 < 0.017, HR 0.525, 95% CI 0.348–0.791). There were significant differences in ORR among the three groups (71.9% vs. 85.4% vs. 92.2%, P = 0.044), and multiple comparisons suggested that the ORR in the nPP group was significantly higher than that in the DDP group (92.2% vs. 71.9%, P = 0.013 < 0.017). However, there was no significant difference in ORR between the TP group and the DDP group (85.4% vs. 71.9%, P = 0.157); increasing the sample size may be able to observe a statistical difference between the two groups. The cisplatin-alone group in our study seemed to have done much worse than what was reported in the EMBRACE I trial [25], which may be related to the higher clinical stage of the patients in the groups we enrolled. Increasing the number of patients could further refine our study. The incidence of AEs was higher in the TP and nPP groups than in the DDP group. However, the differences were not statistically significant (P > 0.05), indicating that the safety of combining paclitaxel or nab-paclitaxel with single-agent cisplatin was tolerable.

A phase II clinical study published by the GOG in 2012 investigated the efficacy and safety of nab-paclitaxel monotherapy in patients with advanced and recurrent cervical cancer. It showed that nab-paclitaxel has considerable activity and moderate toxicity in treating resistant, metastatic, and recurrent cervical cancer [11]. Li et al. [26] employed a combination of nab-paclitaxel and nedaplatin for patients with advanced and recurrent cervical cancer. Their findings showed an ORR of 50.0%, an OS of 16.6 months, a PFS of 9.1 months, and a Grade 3 incidence of thrombocytopenia and anemia at 7.4% and 18.5%, respectively. And no cases of hypersensitivity reactions were reported, suggesting that nab-paclitaxel presents encouraging efficacy and acceptable toxicity profiles. Currently, nab-paclitaxel is approved as a second-line treatment option for patients with recurrent/metastatic cervical cancer. Yu et al. [27] investigated the effect of neoadjuvant chemotherapy consisting of nab-paclitaxel and platinum (NACT-nPP) in patients with LACC. It showed that 72 (92.3%) patients in the NACT-nPP group and 96 (82.1%) patients in the control group achieved CR (P = 0.042). Grade 3 or higher acute hematologic AEs were manageable in the NACT-nPP group (46.2%, 36/78), demonstrating the efficacy and safety of nab-paclitaxel neoadjuvant therapy combined with CCRT for LACC. However, despite these findings, there is still debate about whether neoadjuvant therapy confers tangible benefits to LACC patients and currently, most LACC patients continue to receive primary treatment through CCRT [28].

This study compared the efficacy and safety of three chemotherapy regimens of single-agent cisplatin, paclitaxel plus cisplatin, and nab-paclitaxel plus cisplatin combined with radiotherapy in the treatment of LACC. The results showed that the two cisplatin-based double-agent chemotherapy regimens were associated with improved outcomes than the single-agent cisplatin regimen, and the AEs were tolerable. Compared with traditional paclitaxel, albumin-bound paclitaxel was associated with improved outcomes in OS, PFS, and ORR of LACC, along with improved treatment compliance of patients. Nonetheless, it’s crucial to acknowledge that this study was a single-center retrospective study, the retrospective nature could introduce potential selection biases. Additionally, the sample size was relatively small, the follow-up period was comparatively short, and at data cutoff, outcomes for many patients remained unknown. Consequently, further validation through larger-scale, prospective studies is required to substantiate these findings.