Dosimetric analysis of the effects of the bladder volume on Organs at Risk (OARs) in high-dose-rate intracavitary brachytherapy in locally advanced carcinoma cervix (Stage IB3, IIA2, IIB–IVA)

1. Introduction

Cervical carcinoma remains a significant global health concern for women. According to the International Agency for Research on Cancer (IARC), the specialized cancer agency of the World Health Organization (WHO), cervical cancer is the fourth most frequently diagnosed cancer among women, with about 1800 women being diagnosed with cervical cancer and almost 1000 women dying from it every day, as of 2022 [1]. Although incidence has declined in many high-income countries due to screening and human papillomavirus (HPV) vaccination, rates remain high in regions such as Latin America, sub-Saharan Africa, India, and parts of Asia, largely reflecting disparities in access to prevention and screening programs [2]. High-burden populations typically exhibit low screening coverage combined with a high prevalence of persistent HPV infection [2].

According to the International Federation of Gynecology and Obstetrics (FIGO) 2018 revision, cervical carcinoma is classified into four clinical stages, with staging based on a combination of clinical findings and modern imaging modalities. In this system, stage IB is subdivided into IB1 (tumor ≤2 cm), IB2 (tumor >2 cm and ≤4 cm), and IB3 (tumor >4 cm), reflecting the prognostic impact of tumor size [3].

The primary treatment for early-stage cervical cancer involves either surgery or radiotherapy (RT). Surgery is generally preferred for stages IA, IB1, and selected IIA1 cases, particularly in women seeking fertility preservation [2, 4]. For more advanced stages (IB3 to IVA), concurrent chemoradiation is recommended as the standard of care [5]. A critical component of definitive treatment is intracavitary brachytherapy, which, when omitted or inadequately delivered, is associated with poorer local control and survival outcomes. However, brachytherapy also exposes adjacent organs at risk (OARs) to potentially significant radiation doses. Bladder complications may include acute and chronic cystitis, hematuria, contracted bladder, and fistula formation. The therapeutic challenge is therefore to maximize tumor dose while minimizing OAR exposure [6].

In 2006, the Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology (GEC-ESTRO) published recommendations on three-dimensional (3D) image-guided brachytherapy, including target definitions and dose-volume histogram (DVH) parameters. These guidelines have enabled more accurate dosimetric evaluations compared with the traditional International Commission on Radiation Units (ICRU) point-dose system [2, 5]. Despite these advances, there remains no clear consensus on optimal bladder filling protocols. Recommendations range from an empty bladder with indwelling catheterization to controlled partial filling (e.g., 50 cc) or a fully distended bladder. The ICRU 89 report does not provide specific guidance on bladder volume during pelvic brachytherapy [7].

Recent image guided brachytherapy and Magnetic Resonance (MR) guided radiotherapy studies continue to report inconsistent effects of bladder filling on pelvic organ doses. Some groups use a controlled bladder preparation protocol in which saline is instilled to achieve a predefined bladder volume, usually about 90 to 240 mL. These studies show that a reproducible, moderately filled bladder can maintain high risk clinical target volume (HR-CTV) coverage within prescription goals while keeping bladder, rectum, and sigmoid D2cc within commonly accepted EQD2 limits [8].

In addition, larger bladder volumes have been associated with lower sigmoid D2cc in cervical cancer brachytherapy, consistent with the idea that bladder filling can shift portions of the sigmoid and small bowel away from the applicator region.

Other work indicates the opposite pattern. When anatomy brings the bladder base closer to the tandem and ovoids, bladder D2cc can increase, even if rectal dose falls. For example, in a 2025 series comparing two packing strategies within the same patients, the use of a rectal retractor lowered rectal D2cc but produced a higher bladder D2cc than standard gauze packing [9].

These findings suggest that small geometric shifts near the applicator can raise bladder wall dose despite efforts to protect the rectum.

Adaptive MR linac data in cervical cancer further show that day to day variation in bladder volume changes both target coverage and organ at risk dose. Investigators using daily MR guidance reported that fluctuations in bladder filling significantly altered dose to the bladder, rectum, and clinical target volume, and concluded that active control of bladder volume is necessary for consistent pelvic dose delivery [6].

Given these conflicting observations, there is still no consensus on the optimal bladder volume to use during high dose rate intracavitary brachytherapy for cervical cancer.

The present study evaluates how bladder volume influences D2cc to bladder, rectum, and sigmoid, and HR CTV D90, in women with locally advanced cervical cancer treated with definitive chemoradiation and high dose rate intracavitary brachytherapy, FIGO 2018 stages IB3, IIA2, IIB to IVA.

2. Materials and methods

This retrospective study was conducted at the Department of Radiotherapy, Ahsania Mission Cancer and General Hospital (AMCGH), Dhaka, Bangladesh, from September 2019 to April 2020. A total of 90 patients with histologically confirmed, locally advanced carcinoma of the cervix (FIGO 2018 stages IB3, IIA2, IIB–IVA) were included. Patients were grouped according to bladder volume measured on treatment-planning Computed Tomography (CT) scan:

• Group A: 0–40 cc;

• Group B: 41–80 cc;

• Group C: 81–120 cc.

Each group consisted of 30 patients. Purposive sampling was applied.

Inclusion criteria were: age ≤75 years, Karnofsky performance status ≥60, adequate hematological parameters, and suitability for curative chemoradiotherapy. Exclusion criteria included early-stage or metastatic disease, prior pelvic radiotherapy, vesicovaginal or rectovaginal fistula, recurrent tumors, synchronous malignancy, pregnancy, or uncontrolled comorbidities.

3. Results

The baseline characteristics of the 90 enrolled patients are shown in Table 1. The mean age across groups was similar (45.9–46.6 years), with no statistically significant difference (p = 0.88). The majority of patients had squamous cell carcinoma (89%), while adenocarcinoma accounted for approximately 11%. Most patients presented with FIGO 2018 stage IIB or IIIB disease, with no significant stage imbalance among groups (p = 0.62). Nearly all patients had a Karnofsky performance status ≥70, indicating that the three groups were clinically comparable at baseline (Table 1).

Tumor coverage was adequate and comparable across bladder volume groups (Table 2). The mean HR-CTV D90 EQD2 ranged from 82.8 Gy in Group C to 84.2 Gy in Group B, with no statistically significant differences observed (p = 0.48). Nearly all patients achieved HR-CTV coverage within protocol-recommended levels (>80 Gy EQD2), confirming that variation in bladder volume did not compromise target dose delivery (Table 2).

Dosimetric outcomes for organs at risk are summarized in Table 3. Bladder D2cc EQD2 differed significantly between groups (p = 0.002). Patients in Group B (41–80 cc bladder volume) had the lowest mean bladder D2cc (73.2 Gy), which was significantly lower than both Group A (85.6 Gy) and Group C (78.9 Gy). Rectal D2cc also varied across groups (p = 0.01), with the lowest mean dose observed in Group B (64.5 Gy). In contrast, sigmoid D2cc values were not significantly different among the three groups (p = 0.41). Effect size analysis suggested a moderate impact of bladder volume on bladder and rectal doses, but minimal influence on sigmoid dose (Table 3).

Exploratory stage-wise analyses demonstrated that the trend of reduced bladder and rectal doses in the 41–80 cc group was consistent across both early (IB3–IIA2) and advanced (IIB–IVA) stages, with no significant stage–volume interaction (p > 0.05) (Table 4).

Fig. 1 illustrates the mean D2cc EQD2 values for bladder, rectum, and sigmoid across the three bladder volume groups. Patients in Group B (41–80 cc) consistently demonstrated lower bladder and rectal D2cc compared to Groups A and C, with statistically significant differences (p = 0.002 and p = 0.01, respectively). Sigmoid doses showed minimal variation and did not differ significantly among groups (p = 0.41) (Fig. 1).

Fig. 1.Bar graph of mean bladder, rectum, sigmoid D2cc EQD2. EQD2: Equivalent Dose in 2 Gy fractions.

Fig. 2 presents the distribution of mean bladder volumes across the study groups. The mean measured bladder volumes were 32.4 cc in Group A, 62.7 cc in Group B, and 102.3 cc in Group C, with relatively narrow standard deviations within each group (Fig. 2).

Fig. 2.Distribution of bladder volumes across groups.

At first follow-up (6–8 weeks after completion of treatment), 73.3% of patients achieved a complete response, 20% had a partial response, and 6.7% demonstrated stable disease. The distribution of response outcomes was similar across bladder volume groups, with no statistically significant differences (p = 0.57). Recurrence rates, late toxicity, and survival data were not yet available and are acknowledged as limitations of the study (Table 5).

4. Discussion

This study assessed the dosimetric influence of bladder volume variation on organs at risk (OARs) during high-dose-rate (HDR) intracavitary brachytherapy for locally advanced cervical carcinoma (stages IB3, IIA2, IIB–IVA). The key finding was that a moderately filled bladder (41–80 cc) provided the most favorable dosimetric profile, with significantly lower doses to both the bladder and rectum, while maintaining adequate tumor coverage.

In our cohort, the mean bladder D2cc EQD2 was 85.6 Gy in Group A (≤40 cc), 73.2 Gy in Group B (41–80 cc), and 78.9 Gy in Group C (≥81 cc). The difference was statistically significant (p = 0.002), with the lowest dose observed in the moderate volume group. Rectal D2cc values followed a similar pattern: 70.2 Gy, 64.5 Gy, and 72.4 Gy for Groups A, B, and C, respectively (p = 0.01). In contrast, sigmoid D2cc values—62.3 Gy, 61.8 Gy, and 63.5 Gy across the three groups—did not differ significantly (p = 0.41). These results indicate that bladder volumes around 60 cc are associated with reduced bladder and rectal exposure, without significantly altering sigmoid dose.

Our findings are in line with those of multiple studies, who also reported reduced rectal or sigmoid doses with moderate bladder filling, although effects on bladder dose varied [8, 10]. Harmon et al. [11] similarly concluded that controlled bladder filling optimized OAR sparing. Conversely, excessive bladder distension has been associated with elevated doses to the bladder base, which aligns with the rise in bladder dose we observed in Group C [9].

Target coverage remained consistent across groups, with mean HR-CTV D90 EQD2 of 83.5 Gy in Group A, 84.2 Gy in Group B, and 83.7 Gy in Group C (p = 0.48). This confirms that variation in bladder volume did not compromise tumor dose delivery. Sharma et al. [12] similarly reported that bladder filling strategies did not adversely affect HR-CTV coverage, supporting the clinical applicability of moderate bladder filling protocols.

Although the study was primarily dosimetric, early treatment response was also evaluated. At 6–8 weeks post-treatment, 73.3% of patients achieved a complete response, 20% had a partial response, and 6.7% had stable disease, with no significant differences across bladder volume groups (p = 0.57). These figures are broadly comparable to published series of HDR brachytherapy, where complete response rates often range from 70% to over 90% [13, 14]. The slightly lower Complete response (CR) rate in our study may reflect differences in assessment methods, patient selection, or shorter follow-up duration.

While bladder filling during brachytherapy has been investigated in previous studies, most reports originate from Western or East Asian centers. Our study provides data from a South Asian cohort, thereby contributing regional evidence to an ongoing clinical debate. Moreover, the use of stratified bladder volume groups and reporting of EQD2 values enhances interpretability and clinical relevance. The addition of short-term clinical response data, albeit limited, provides further context for the dosimetric findings.

Several limitations must be acknowledged. This was a retrospective study with purposive sampling, which introduces potential selection bias. Bladder volume was measured only once per patient, without accounting for inter-fraction variation. CT planning was performed with 5-mm slice thickness, which is less precise for contouring small structures compared to the 2–3 mm slices recommended in contemporary practice [2, 7]. The study was also limited by modest sample size and lack of long-term follow-up for toxicity and survival outcomes. Nonetheless, this revised analysis incorporated effect size and significance reporting in line with best practices [15].

Despite these limitations, the findings support the practice of maintaining a moderately filled bladder (~60 cc) during HDR intracavitary brachytherapy for cervical cancer. This approach minimizes bladder and rectal doses without compromising tumor coverage. However, the results should be interpreted as identifying a beneficial trend rather than a strict cut-off, as individual anatomical and clinical factors must be considered. Prospective studies with repeated bladder volume measurements, standardized imaging protocols, and incorporation of long-term clinical outcomes are needed to confirm these observations.

5. Limitations of the study

This study has several important limitations. First, its retrospective design and relatively small and older (2019–2020) sample size limit the statistical power and the ability to detect subtle differences, particularly with respect to clinical outcomes. Second, bladder volume was assessed only once per patient, and inter-fraction variability could not be captured. Third, CT simulation was performed using 5-mm slice thickness, which may reduce contouring accuracy compared to thinner slices recommended in contemporary practice. Fourth, the study was conducted at a single institution, which may limit the generalizability of the findings to broader populations. In addition, purposive sampling may have introduced selection bias. Long-term clinical outcomes, including late toxicity, local control, and survival, were not available, restricting the interpretation of the dosimetric findings in terms of clinical relevance. Financial and logistical constraints also limited the range of investigations and follow-up assessments. Finally, multivariable analysis to adjust for potential confounders such as stage, applicator type, and tumor volume was not feasible due to missing data and insufficient statistical power. Despite these limitations, the consistency of the observed dosimetric trends across both early (IB3–IIA2) and advanced (IIB–IVA) stages lends support to the robustness of our findings. Prospective, multicenter studies with larger sample sizes, repeated bladder volume assessments, thinner imaging slices, and long-term outcome data are required to validate and extend these results.

6. Conclusions

This study demonstrates that bladder volume significantly influences dosimetric parameters for organs at risk during HDR intracavitary brachytherapy in locally advanced cervical cancer. Patients with a moderately filled bladder (41–80 cc, mean ~60 cc) showed the lowest bladder (73.2 Gy) and rectal (64.5 Gy) D2cc doses compared with smaller or larger volumes, while sigmoid dose remained unaffected. Importantly, tumor coverage was not compromised, with all groups achieving adequate HR-CTV D90 EQD2 (>80 Gy). Early response rates were comparable across groups, with complete response observed in 73.3% of patients. Overall, maintaining a bladder volume of approximately 60 cc appears optimal for minimizing bladder and rectal radiation doses without impairing tumor control.

7. Recommendation

A controlled bladder filling protocol aiming for ~60 cc should be considered during HDR intracavitary brachytherapy in cervical cancer patients, particularly in resource-limited settings where individualized adaptive planning may not be feasible. Multicenter prospective studies with larger cohorts, repeated bladder measurements, advanced imaging with thinner CT/MRI slices, and long-term follow-up are needed to confirm these findings and assess their impact on late toxicity and survival. Incorporating standardized bladder filling guidelines into institutional protocols may improve consistency and dosimetric outcomes.

Availability of data and materials

This study used retrospective hospital records and radiotherapy planning data from Ahsania Mission Cancer and General Hospital. The anonymized dataset is available upon request.

Author contributions

RK and QC—conceived the study, defined the research question, and designed the study protocol. RK, SJM and JF—collected clinical data, treatment records, bladder volume measurements, and dose volume histogram outputs from the institutional archive. RK and SJM—reviewed applicator placement, target contours, and organ at risk contours for all cases. RK and JF—curated the dataset, calculated EQD2 values, and performed the statistical analysis. QC—contributed to clinical interpretation of the dosimetric findings and their relevance for practice. RK—rafted the manuscript. QC, SJM and JF—critically reviewed the manuscript for important intellectual content and provided revisions.

Ethics approval and consent to participate

This was a retrospective study of patients with locally advanced cervical carcinoma. The Institutional Ethical Review Committee of Ahsania Mission Cancer and General Hospital approved the study protocol (Ref: DAM/AMCGH/1900-2019/1882; DSN: 2021-07-0003). Written informed consent was obtained from all participants, ensuring confidentiality and voluntary participation.

Acknowledgment

We thank the radiation therapy technologists, anesthesia team, oncology nursing staff, and medical physics staff of Ahsania Mission Cancer and General Hospital for their support during simulation, applicator insertion, image acquisition, treatment planning, and delivery of brachytherapy. We also thank the medical records and radiotherapy planning office staff at Ahsania Mission Cancer and General Hospital for help with secure retrieval of archived treatment plans and follow up documentation. No professional medical writing or editorial assistance was used.

Funding

This research received no external funding.

Conflict of interest

The authors declare no conflict of interest.