1. Introduction

Cervical cancer is the fourth most common malignancy in women and remains a leading cause of cancer-related morbidity worldwide [1, 2]. With increasing population size and rising life expectancy, more women over the age of 65 years are being diagnosed, often at more advanced stages and with higher rates of comorbidities and overall poorer health status [3, 4]. As a result, they may receive less curative treatment due to reduced tolerance. Still, research has shown that older women who undergo curative treatment can achieve survival rates comparable to those of younger women, although toxicities, particularly those related to radiotherapy (RT) and/or chemotherapy (CT), are more frequent in older patients [5, 6].

For early-stage cervical cancer, treatment options include surgery or definitive RT with brachytherapy (BRT), while chemoradiotherapy (CRT) is considered the standard for locally advanced disease [7]. Concurrent CRT (CCRT) has been shown to reduce local and distant recurrence, delay disease progression, and improve disease-free survival (DFS) compared with RT or CT alone [8]. However, the role of concurrent CT in older patients remains debated. Some studies have suggested that CCRT offers no significant survival benefit in this group [9], while others report similar outcomes for younger cohorts, aside from increased non-hematological toxicities [10]. Despite their higher burden of comorbidities and frailty, older patients have been shown to tolerate standard regimens for gynecological cancers [11]. Moreover, age alone may play a less decisive role in prognosis, and treatment intensity is best determined by overall health status rather than chronological age [12].

The aim of this study was to evaluate survival outcomes, treatment efficacy, and toxicities in patients aged ≥65 years with cervical cancer who underwent definitive CCRT or RT alone. A further objective was to assess whether treatment strategies and prognosis differed between those aged 65–75 years and those aged >75 years.

2. Methods

3. Results

3.2 Oncological outcomes

The median follow-up was 48 months (range: 6–243 months). At the last follow-up, 258 patients (56.5%) were alive, and 200 patients (43.5%) had died, of whom 92 (20.1%) had died of their disease. In the younger elderly group, 60 patients (18.5%) died of cervical cancer, compared with 32 patients (24.1%) in the older elderly group (p = 0.07). Mortality from causes other than cervical cancer was significantly higher in the older group than in the younger group (33.8% vs. 18.4%, p < 0.0001).

The clinical complete response rate after therapy was higher in the younger elderly group than in the older group (83.1% vs. 72.9%, p < 0.0001). Survival rates according to age groups are presented in Table 2. For all patients, the 5-year overall survival (OS) and cancer-specific survival (CSS) rates were 61.6% and 77.5%, respectively. The 5-year OS was 67.3% in the younger elderly group and 46.1% in the older elderly group (p < 0.0001). The 5-year CSS was 80% in the younger group and 71.1% in the older group, but this difference was not significant (p = 0.77).

Table 2.Results of the multivariate analysis showing the prognostic value of different clinicopathological parameters.

Characteristics	Overall survival	Cancer-specific survival	Disease-free survival	Distant metastasis-free survival
	HR (95% CI)	p value	HR (95% CI)	p value	HR (95% CI)	p value	HR (95% CI)	p value
Age	1.32 (1.01–1.92)	0.042	1 (0.64–1.71)	0.83	0.61 (0.37–1.00)	0.052	0.88 (0.51–1.52)	0.66
Performance status	1.91 (1.23–2.97)	0.004	1.8 (0.96–3.39)	0.067	2.21 (1.25–3.92)	0.006	1.62 (0.83–3.17)	0.15
Tumor size	1.22 (0.89–1.66)	0.20	1.12 (0.70–1.80)	0.62	1.30 (0.82–2.00)	0.25	1.62 (0.95–2.76)	0.074
Histopathology	1.02 (0.81–1.27)	0.85	1.12 (0.85–1.49)	0.40	1.22 (0.95–1.57)	0.11	1.36 (1.03–1.80)	0.028
Lymph node metastases	1.77 (1.31–2.39)	<0.0001	1.85 (1.19–2.88)	0.006	1.72 (1.14–2.61)	0.01	2 (1.31–3.35)	0.002
Type of treatment (RT or CRT)	0.53 (0.38–0.74)	<0.0001	0.75 (0.44–1.26)	0.28	0.78 (0.47–1.29)	0.34	0.81 (0.46–1.44)	0.49
Brachytherapy application	0.80 (0.50–1.27)	0.34	0.71 (0.36–1.39)	0.32	0.75 (0.39–1.44)	0.39	0.55 (0.28–1.07)	0.083
Treatment Response	0.29 (0.22–0.38)	<0.0001	0.21 (0.15–0.30)	<0.0001	0.23 (0.17–0.33)	<0.0001	0.33 (0.22–0.49)	<0.0001
Abbreviations: CI: confidence interval; HR: hazard ratio; RT: Radiotherapy; CRT: chemoradiotherapy.

Ninety-three of the 458 patients did not receive concurrent CT. Among the younger elderly patients, 40 (12.3%) treated with RT alone had a 5-year OS of 53.3%, compared with 68.8% in the 285 patients (87.7%) who received CCRT (p = 0.157). In the older elderly group, 53 patients (39.8%) treated with RT alone had a 5-year OS of 32.4%, whereas the 80 patients (60.2%) who received CCRT achieved a survival rate of 55.3% (p = 0.001) (Fig. 1). The 5-year CSS was 71.3% in older elderly patients who received CRT and 80.6% in the younger elderly group, with no significant difference (p = 0.285). Similarly, 5-year DFS and local control rates did not differ significantly between the two age groups when both received CRT. Among patients who received CRT, the 5-year locoregional control rate was 90.6% in the younger group and 92.9% in the older group (p = 0.532). Among those who received CRT followed by BRT, the 5-year locoregional control rate was 91.3% in the younger group and 92.2% in the older group (p = 0.481). In this subgroup, the 5-year DFS was 77.3% in both age groups (p = 0.551).

Fig. 1.Kaplan-Meier plots of overall survival, (A) radiotherapy (B) chemoradiotherapy for patients aged 65 to 74 years (blue line) and ≥75 years (green line).

Local recurrence (LR) occurred in 32 patients (7%), including 25 younger elderly patients. DM developed in 81 patients (17.7%), 54 of whom were in the younger elderly group. There was no significant difference in LR or DM rates between age groups. The most common isolated organ metastasis was lung metastasis, found in 26 patients (33.3%), followed by liver metastasis in 6 patients (7.7%). Multiple organ metastases occurred in 29 patients (37.2%), and other organ metastases in 20 patients (21.8%).

3.4 Toxicity assessment

Acute and chronic toxicity rates for all patients are shown in Fig. 2. No significant differences were observed in acute or late complications between age groups. All patients were evaluated for acute toxicity. No grade 3 toxicity occurred in patients treated with RT alone. Among the younger elderly who underwent CRT, grade 3 acute gastrointestinal toxicity was observed in seven patients (2.2%): proctitis in two patients, diarrhea in four patients, and vomiting in one patient. In addition, one younger elderly patient (0.3%) developed grade 3 cystitis during CRT. In the older elderly group, no grade 3 gastrointestinal or genitourinary toxicity was observed. Grade 3–4 hematological toxicity developed in 16 patients (6.8%) who underwent CRT; 12 were in the younger elderly group and 4 in the older elderly group.

Fig. 2.Bar graphics demonstrate the incidence of acute (A) gastrointestinal (GI), (B) genitourinary (GU), (C) hematological toxicity, and chronic (D) gastrointestinal (E) genitourinary toxicity.

Late severe gastrointestinal toxicity was observed in six patients (1.9%), all in the younger elderly group. Radiation proctitis occurred in three patients receiving CRT and two patients receiving RT, while a rectovaginal fistula developed in one patient receiving CRT. Late cystitis was observed in three younger elderly patients (0.9%) treated with CRT.

4. Discussion

In this study, we observed that among patients with cervical cancer, those older than 75 years had lower OS rates than those younger than 75 years. However, in the multivariate analysis, age itself was not identified as a significant prognostic factor for CSS, DFS, or DMFS. As expected, mortality due to causes other than cervical cancer was significantly higher in the older group than in the younger group (33.8% vs. 18.4%). In both age groups, patients who received standard CRT followed by BRT demonstrated better survival outcomes, with no significant differences in local control or DFS rates between the two age groups when treated with the standard approach. Nevertheless, administration of CRT and BRT was significantly lower among patients in the older elderly group.

Only a limited number of studies have examined the role of definitive RT in older patients with locally advanced cervical cancer. Previous studies focusing on patients aged 65 years or older are summarized in Table 3 (Ref. [10, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26]); most were retrospective in design, often involving conventional RT [10, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26]. Reported 2- to 5-year OS rates in these studies ranged between 31% and 82%, depending on stage.

In our retrospective cohort, the 5-year OS rate was 61.6% for the entire geriatric population, with 67.3% in the younger elderly group (65–74 years) and 46.1% in the older elderly group (≥75 years). These findings are consistent with prior reports, including those by Mitchell et al. [17] (46% OS for ≥70 years), Sakurai et al. [19] (33% OS for ≥80 years), Ikushima et al. [21] (49% OS for 75–92 years), and Sarma et al. [26] (55.9% OS for 75–85 years). Differences across studies may reflect variations in patient selection, stage distribution, treatment techniques, and follow-up duration. Overall, our results are comparable with those in the literature and reinforce the evidence that advanced age is associated with a poorer prognosis in cervical cancer.

When treated with RT alone, the 5-year OS was 53.3% in the younger elderly group and 39.8% in the older elderly group. For patients treated with CRT, the 5-year CSS rate in our entire cohort was 78.5%, with no significant difference between the two age groups. The local control rate in our series was 91.6%, again with no significant difference between the groups. Together, these results suggest that RT is effective in achieving high local control rates, but CRT provides superior survival outcomes. In clinical practice, concerns about potential complications, particularly in patients over 75 years of age, often lead to less aggressive treatment approaches. Retrospective studies comparing women aged <70 and ≥70 years have shown lower survival in the older group, largely due to a more advanced stage at diagnosis and less curative treatment received [27, 28]. Similarly, a retrospective study of 7848 older patients found that those aged 71–80 and >80 years were less likely to complete standard treatment, resulting in significantly poorer survival outcomes [29]. However, several other studies have demonstrated that optimal treatment strategies can improve survival in older patients with acceptable toxicity, similar to outcomes in younger patients [20, 22]. CRT has been associated with comparable survival benefits in geriatric (≥65) and non-geriatric (<65) populations, and when curative RT or CRT is delivered, survival rates in older patients have been reported to approximate those of younger patients [19, 30]. Consistent with the literature, we observed lower rates of CCRT and BRT administration among patients aged ≥75 years, which contributed to worse survival outcomes in this group. According to a Surveillance, Epidemiology, and End Results Program (SEER) database analysis by Leetanaporn et al. [31], the addition of CT to RT significantly improved OS and CSS in women aged ≥65 years. Another SEER analysis by Liao et al. [32] similarly found that CT added to RT improved OS and CSS in women aged ≥65 years with locoregionally staged cervical cancer, though this benefit was not statistically significant in patients aged ≥80 years.

Lymph node metastasis has been reported as an important prognostic factor in cervical cancer. In a study by You et al. [25], 246 elderly patients treated with definitive RT or CRT were analyzed for oncological outcomes. The authors showed that among patients with negative lymph nodes, there were no differences in OS or DFS between those who did and did not receive CCRT. However, in patients with positive lymph nodes, those who received CCRT achieved better OS and DFS than those who did not [25]. In our study, the presence of lymph node metastasis was similarly found to be a significant prognostic factor for all survival outcomes, both in patients treated with CRT and those treated with RT alone.

BRT is an important component of treatment in locally advanced cervical cancer. In a SEER database analysis [33], patients treated with combined EBRT and BRT had significantly better OS than those treated with EBRT alone (64% vs. 51%). However, numerous studies have shown a decline in the use of BRT with increasing age. One study reported that fewer than 40% of patients aged 71–80 years received BRT, and fewer than 30% of those over 80 years received it [29]. Data analyses of Gynecologic Oncology Group protocols likewise revealed that more than 30% of patients over 70 years were unable to complete BRT, compared with only 13% of patients under 40 years [34]. Nevertheless, several studies have shown that BRT is generally well tolerated in older patients and can improve survival, even in those with comorbidities [35]. For example, in a study by Hanawa et al. [36], among patients aged ≥70 years, RT with daily low-dose cisplatin was administered to 87%, and BRT was applied, yielding a local control rate of 91.5%. In the current study, more than 90.6% of patients received BRT, a higher rate than typically reported in the literature. Only 43 of 458 patients (9.4%) could not undergo BRT following EBRT and instead received an additional external boost dose. In the younger elderly group, 5.2% of patients did not receive BRT, compared with 19.5% in the older elderly group, a significant difference. The local control rates in our cohort were 92.2% with BRT and 84.5% without. The corresponding OS rates were 62.9% with BRT and 41.9% without, consistent with the SEER findings.

We did not observe significant differences in acute or late toxicities between the two age groups. In a study comparing patients with cervical cancer younger than 60 years versus those older than 70 years, grade ≥3 chronic toxicities, particularly gastrointestinal, were significantly higher in the elderly group after propensity score matching [37]. Another study of 43 patients aged <65 years and 23 patients aged ≥65 years treated with definitive CRT or RT reported higher rates of grade 3 hematological and gastrointestinal toxicities in the ≥65-year age group [38]. In a separate study evaluating daily low-dose cisplatin with RT, grade ≥3 hematologic (15%) and gastrointestinal (11%) toxicities were observed, which were lower than rates typically reported with weekly cisplatin administration [36]. In our cohort, grade 3 acute toxicities were observed as genitourinary (0.3%) and hematological (6.8%). Grade 3–4 late toxicities were 0.9% genitourinary and 1.9% gastrointestinal. Unlike prior reports, toxicity rates in our study were lower, and both CCRT and RT were generally well tolerated in elderly patients.

The current study has several notable strengths. First, it includes a large sample size, with real-world data collected from multiple RT centers, enhancing both the reliability and generalizability of the findings. Second, all patients aged 65 years and older completed EBRT, and the majority received CCRT, demonstrating the feasibility of this treatment approach in older patients (including those over 75 years). Finally, the study evaluated multiple prognostic factors affecting OS, CSS, and both local and distant recurrence.

However, several limitations should also be acknowledged. First, the retrospective design prevented a comprehensive geriatric assessment prior to RT, limiting the ability to fully evaluate patient overall health status and its influence on treatment outcomes. Second, the inclusion of patients with varying stages and histopathology of cervical cancer may have introduced heterogeneity into the results. Third, toxicity analysis was based on retrospective review of patient records, which may not have fully captured the extent of treatment-related toxicities. Fourthly, survival was calculated from the date of biopsy, as commonly done in the literature. Although treatment started within an average of 1 month across all age groups, potential delays in elderly patients with comorbidities may still affect survival outcomes Finally, although different RT modalities (3D conformal RT, intensity-modulated RT, or volumetric modulated arc therapy) were used, no significant differences in toxicity outcomes were observed across these techniques. Therefore, we did not present a separate subgroup analysis by RT modality, which should be considered a limitation of the study.

While tumor characteristics were evenly distributed between younger and older elderly patients, our analysis revealed worse survival outcomes in the older group, highlighting a greater treatment need in this population. Based on our findings, RT with CT should be considered for older patients, taking into account pre-RT risk factors and comorbidity scores whenever feasible. Nonetheless, larger prospective randomized trials with well-defined patient populations are needed to validate these results.

5. Conclusions

Overall, our study demonstrated that CCRT and BRT positively impacted survival in patients aged 65 years and older with cervical cancer. Lymph node positivity and a partial or absent response to RT or CRT were associated with worse outcomes. We believe that standard treatment approaches including CRT and BRT should be offered to older patients whenever their clinical condition permits.

Abbreviations

TROD, Turkish Society for Radiation Oncology; RT, Radiotherapy; BRT, Brachytherapy; CRT, Chemoradiotherapy; CCRT, Concurrent chemoradiotherapy; CT, Chemotherapy; FIGO, The International Federation of Gynecology and Obstetrics; 3DCRT, Three-dimensional conformal RT; EBRT, External RT; HDR-BRT, High-rate BRT; PET/CT, Positron emission tomography; MRI, Magnetic resonance imaging; OS, Overall survival; CSS, Cancer specific survival; DFS, Disease free survival; LR, Local recurrence; DM, Distant metastases; DMFS, Distant metastasis-free survival; LRFS, Local recurrence-free survival; GI, Gastrointestinal; GU, Genitourinary; AUC, area under the curve.

Availability of data and materials

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Author contributions

İAÇ, EM—conception and design. HH, MG, SA, ŞAE, Kİ, BS—data curation. İAÇ, ZG, BA, HÖ, DA, CDA, EÖ—anaysis. AS, HB, AE, TB, SK, NM—methodology. FY, ZÖ, İBG, EM—supervision. HH, MG, SA, ŞAE, Kİ, BS, ZG, BA, HÖ, DA, CDA, EÖ, ZG, BA, HÖ, DA—review. İAÇ, CDA, EÖ, AS, HB, AE, TB, SK, NM, FY, ZÖ, İBG—editing. All authors contributed to manuscript writing and approved the final article.

Ethics approval and consent to participate

The study was approved by the Marmara University Faculty of Medicine Clinical Research Ethics Committee (09.2022.840). And all methods were carried out in accordance with the Declaration of Helsinki. Comprehensive consent was obtained from eligible patients in our institution. Besides comprehensive consent, specific informed consent for this study was not required because this was a retrospective study with an opt-out option. This decision was in accordance with the National Research Ethics Review Guideline, Sixth Edition, Chap. 7, Sect. 7.2, and was consistent with the Declaration of Helsinki.

Acknowledgment

We thank the Turkish Society for Radiation Oncology Gynecologic Oncology Working Group and Riza Cetingoz for their support.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for profit sectors.

Conflict of interest

The authors declare no conflict of interest.