At present, there is no standard treatment for patients with locally recurrent cervical cancer. Thus, CCRT should be considered with the selective use of brachytherapy [21, 22]. A retrospective study of 50 patients with isolated para-aortic lymph node recurrence of cervical cancer after radical surgery compared the clinical outcomes of different salvage treatment modes, including RT, CCRT, surgery, chemotherapy, and best supportive care. The results showed that CCRT was an effective salvage treatment for isolated para-aortic lymph node recurrence; the 3-year OS and PFS rates associated with CCRT were 85.7% and 71.4%, respectively [2]. Another retrospective study of 22 cervical cancer patients with lymph node recurrence who previously underwent radical operation showed that salvage RT with concurrent chemotherapy was a good choice for patients; the 5-year PFS and OS rates for all 22 patients were 32.7% and 30.7%, respectively [23]. However, these studies did not explore the prognosis following IMRT for patients with local recurrence. A retrospective study comparing IMRT with conventional RT for patients with recurrent cervical cancer found that IMRT included higher irradiation doses for tumors (61.8 Gy vs. 50.3 Gy), had fewer side effects, and resulted in better prognosis (5-year OS: 35.4% vs. 21.4%; 5-year PFS: 26.1% vs. 15.1%) than conventional RT [24]. In our study, all patients received IMRT for external irradiation. The results showed that IMRT-based salvage treatment resulted in better prognosis and the 5-year OS and PFS rates were 64% and 60.2%, respectively.
The location of recurrence and metastasis is an important factor influencing prognosis. One study showed that the prognosis of para-aortic lymph node metastasis is better than that of supraclavicular lymph node metastasis and that the prognosis of lymph node metastasis is better than that of hematogenous metastasis [6]. In our study, the pelvic cavity was the most common recurrence site, followed by the vaginal stump and extra-pelvic area. Furthermore, the prognosis of patients with vaginal stump recurrence was better.
Whether the time to recurrence is related to prognosis is questionable. Jeon et al. reported that a time to recurrence of > 18 months was associated with better OS and PFS [23]. Singh et al. reported that the time to recurrence > 24 months after the initial therapy was a good prognostic factor [20]. Another study showed that time to recurrence of > 10 months was not significantly associated with OS [7]. Kubota et al. reported that a median time to recurrence of > 10 months, as well as other cutoff values including 10, 18, and 24 months, was not significantly associated with OS, LC, or PFS [2]. This study showed that the cutoff time to recurrence, whether 20 or 24 months, did not influence prognosis but was related to the prognosis with respect to the RT mode.
There are many types of salvage RT for locally recurrent cervical cancer, and these can be summarized as follows: regional RT and local RT [2, 6, 7]. It is unclear as to which mode is better. Sato et al. compared the effects of the two RT modes on the prognosis of patients with oligo-recurrence; 4 patients received gross tumor RT, whereas 17 patients received RT including the regional lymph node area. No significant difference in outcomes was found [9]. However, the number of cases in this study was very small. This study demonstrated that regional RT was associated with better prognosis than local RT. Most patients with stump recurrence who received regional RT had a good prognosis. However, there was no significant difference between the two modes in the prognosis of patients with pelvic and abdominal lymph node recurrence. It was found that patients aged < 51 years, with recurrence time ≤ 24 months, recurrence site=1, and SIRI less than the cutoff value seem to be more suitable for regional RT.
Both SIRI and PLR are biomarkers of systemic inflammatory response, which can reflect the tumor microenvironment. Many studies have shown that SIRI, a new systemic inflammatory response biomarker, is a better prognostic factor than other biomarkers, and a high SIRI is associated with poor prognosis of patients with various malignancies [13, 14, 25–27]. In addition, SIRI can change dynamically with changes in tumor burden and immune response status in cervical cancer patients, and patients with a decrease in SIRI of > 75% had better prognosis (p < 0.001). SIRI was also a potential marker for therapeutic response monitoring in patients with curable cervical cancer [12]. PLR is associated with prognosis but is not an independent prognostic factor in many types of cancers [12, 14, 27]. Furthermore, this study showed that SIRI was a prognostic factor for patients with locally recurrent cervical cancer but not PLR, which is consistent with previous results.
Other factors, such as initial stage and treatment, pathological pattern, and salvage RT with or without chemotherapy, did not influence prognosis. Salvage CCRT was not shown to improve prognosis when compared with RT alone in this study, which is inconsistent with the results of many other studies [21, 23]. This may be related to the imbalance in the number of cases between the chemoradiotherapy and RT groups.
Our study had some limitations. First, this study was a retrospective study performed at a single institution. Second, this study involved a relatively small number of patients. Future studies should consider including a larger sample size or employing a randomized clinical study design to validate these preliminary results.
In conclusion, patients with locally recurrent cervical cancer who received IMRT-based salvage RT had good prognosis. Vaginal stump recurrence, regional RT, and a low SIRI predict better survival. Further analysis showed that when the time to recurrence is ≤ 2 years or the recurrence site is the vaginal stump, regional RT is recommended.