As the age at which women develop cervical cancer is decreasing and radiation may have serious implications that reduce the quality of patients’ life, reducing radiation is an important challenge for patients with LACC. In this study, our results revealed that NACT with paclitaxel and carboplatin significantly reduced the clinicopathological risk factors and cumulative adjuvant radiation rate when compared to the PRS group, without compromising the survival. These findings may provide important help in the management of LACC to improve the quality of life.
Though concurrent chemoradiation is recommended as the standard treatment for patients with LACC, as the age at which women develop cervical cancer is decreasing, treatment that protects physiological function and improves quality of life is important, and radical surgery has been chosen for LACC. However, after radical surgery, some patients still present with pelvic lymph node metastasis, parametrial involvement, positive surgery margin, LVSI and deep stromal invasion, which are identified as risk factors for recurrence and death (11, 12), and adjuvant radiation is recommended if patients exhibit these risk factors. These patients are then faced with increased treatment and complications.
In an effort to improve the prognosis and quality of life of patients with LACC, NACT followed by radical surgery has been proposed as a promising strategy for LACC (13), which was believed to be able to reduce the risk factors of recurrence and death, and reduce the need for postoperative adjuvant radiotherapy. According to a randomized study, the pelvic lymph node metastasis (25.0% vs 42.9%, P = 0.025) and parametrial infiltration (25.0% vs 41.4%, P = 0.038) rates were significantly lower in the NACT (with cisplatin, mitomycin and 5-fluorouracil) group than in the PRS group (14). Yang et al. reported in their multicenter study that the incidence of LVSI and deep stromal invasion were both significantly reduced after NACT with IP and TP when compared to the PRS group (4.7% vs 18.2%, P = 0.002; 45.8% vs 68.2%, P = 0.001) (3), and Kim et al. also obtained similar results in their study with NACT consisting of paclitaxel/carboplatin, 5-fluorouracil/cisplatin and 5-fluorouracil/carboplatin (15). In this study, we observed that the rates of patients with tumor > 2cm and deep stromal invasion in the NACT group were significantly lower than those in the PRS group, while there were more patients with more advanced stages and larger primary tumor sizes in the NACT group.
Regarding postoperative radiation, our results showed that the cumulative radiation rate was significantly reduced in the NACT group compared to the PRS group (54.7% vs 65.1%; P = 0.041), especially for the responders. Similarly, another study with NACT consisting of paclitaxel and cisplatin/carboplatin also reported that the adjuvant radiotherapy was administered to less patients in NACT group compared to PRS group (13). Katsumata N revealed that the proportion of patients who met the criteria for postoperative radiation (72% vs 89%, P = 0.015) and patients who received postoperative radiation (58% vs 79%, P = 0.015) were both significantly lower in the NACT group than in the PRS group (6). Yang et al also reported that the rates of postoperative adjuvant radiotherapy and chemoradiation in the NACT group were lower than that of the PRS group, though without significant difference (3).
While the short-term efficacy of NACT is certain, whether NACT affects locally advanced cervical cancer patients with long-term survival remains controversial (16, 17). Yin et al. performed a retrospective study to compare the long-term survival of NACT followed by radical surgery and primary radical surgery, and the results showed that the NACT group had significantly higher PFS (HR = 1.870, P = 0.0031) and OS (HR = 1.813, P = 0.0175) rates than the PRS group (16). However, there were also studies that failed to obtain similar results. A phase III trial was conducted to determine whether NACT impacts the survival of LACC, and it finally failed to find any benefit of NACT group, with similar PFS rates (56.2% vs 53.8%) and OS rates (63.3% vs 60.7%) in the NACT group compared to the PRS group (18), which was in consistence with our previous study (19). In the present study, the 5-year OS and PFS of the NACT group (78.3% and 64.5%) were similar to those of the PRS group (83.0% and 70.6%). All these results indicated that NACT may be useful for improving the survival of patients with LACC or may confer comparable survival, it at least did not worsen the long-term survival.
Our study clarified the impact of carboplatin-paclitaxel NACT on postoperative risk factors and cumulative radiotherapy in patients with LACC. However, it had several limitations. First, it was a single-center retrospective study in which selection bias and confounding bias were inevitable; second, the patients in NACT group and PRS group were not very well matched; third, in terms of OS and PFS, we did not make comparisons to concurrent chemoradiation, which is also effective against LACC. Thus, further multicenter and randomized trials are need to verify the effect of NACT on adjuvant radiation.