Low Risk for Ureteral Stricture From Cervical Cancer Brachytherapy

Pam Harrison

April 24, 2018

Despite previous concerns that brachytherapy for locally advanced cervical cancer may increase the risk for ureteral stricture, reassuring data from two large international studies show that this is not the case for most patients.

The two trials evaluated outcomes after image-guided adjusted brachytherapy (IGABT), during which radiation is delivered either through an applicator placed in the uterus (intracavitary [IC] brachytherapy), or by inserting needles directly into the tumor (interstitial [IS] brachytherapy), or by a combination of these two techniques.

"With IGABT, you risk increasing the dose of radiation to the parametria, especially in large tumors, and this might contribute to an increased risk for stricture," Lars Fokdal, MD, PhD, a consultant at the Aarhus University Hospital, Denmark, explained to Medscape Medical News in an email.

"But our results showed that this is not the case, as strictures were only associated with tumor stage and hydronephrosis at baseline, so patients should be informed about this risk, and it should be kept in mind during follow-up," he added.

Dr Fokdal presented the new data at the ESTRO37 conference in Barcelona, Spain.

In patients with locally advanced cervical cancer who are treated with IGABT, severe to life-threatening ureteral stricture occurred rarely for patients with stage I-II cancer as well as for those with stage III-IV in the absence of hydronephrosis at diagnosis, but the risk for ureteral stricture was considerable for patients with stage III-IV disease with hydronephrosis at diagnosis, he concluded.

Updated Analysis

The updated analysis presented at the conference involved a total of 1860 patients with locally advanced cervical cancer who participated in the retrospective RetroEMBRACE study (n = 610) and the prospective EMBRACE study (n = 1250).

"Treatment included external-beam radiotherapy with prescribed dose 45 to 50 Gy in 25 to 30 fx [fractions] with concomitant cisplatin in 89% of patients," the authors note.

Fifty-eight percent of patients received high-dose-rate brachytherapy, while 42% of patients received pulse-dose-rate brachytherapy. Fokdal explained that with high-dose-rate brachytherapy, practitioners deliver the whole dose at one time, whereas with pulse-dose-rate brachytherapy, they deliver many smaller doses — for example, they could deliver 20 doses within 20 hours.

"Brachytherapy was delivered with the combined IC/IS technique in 36% of the patients," the researchers note.

Both procedures are performed with CT or MRI guidance. This enabled practitioners know the exact position of the tumor, thereby allowing precise targeting of treatment. The total mean radiation dose delivered to the most exposed 2 cm2 of the bladder in the studies analyzed was 78.1 Gy, the researchers state.

At a median follow-up of 34 months, 32 patients had developed grade 3 to 4 ureteral stricture, Fokdal and colleagues report.

This meant that the actuarial risk for grade 3 to 4 ureteral stricture following IGABT was 1.7% at 3 years and 2.2% at 5 years, they add.

This risk was even lower among those with tumors of stages T1 to T2. These included the majority of patients involved in both studies. For those with T1 tumors, the actuarial risk for grade 3 to 4 ureteral stricture following IGABT was 0.4% at 3 years and 1.0% at 5 years.

For those with T2 tumors, the actuarial risk for ureteral stricture following IGABT was 1.1% at both 3 and 5 years.

A small number of patients presented with tumors of stage T3 to T4 at diagnosis. For patients who did not have hydronephrosis on presentation, the actuarial risk of developing a ureteral stricture after IGABT was 2.2% at 3 years and 4.8% at 5 years.

In contrast, for patients with tumors of stage T3 to T4 accompanied by hydronephrosis at diagnosis, the actuarial risk of developing a ureteral stricture at both 3 and 5 years after IGABT was 11.5%. Fokdal explained that hydronephrosis is due to pressure from the tumor with involvement of the parametria and, eventually, the pelvic wall.

"In order to cure the patient, you therefore prescribe a higher dose in this area, which subsequently results in a higher risk for morbidity," he said. To avoid ureteral stricture in the subset of patients who are at higher risk for stricture, physicians need to follow patients more closely after they receive IC/IS IGABT so as to be able to identify any stricture that might develop early, before the stricture becomes severe, he said.

Practitioners could also consider inserting a ureteral stent prior to radiotherapy so as to visualize the ureter on imaging.

"It is good to know that the interstitial component of IGABT does not increase the risk of this relatively rare but sometime serious complication," Fokdal noted.

"However, the risk is more pronounced in patients with advanced-stage disease and hydronephrosis at diagnosis," he cautioned.

The investigators also cautioned that an increased risk for ureteral stricture cannot be ruled out in patients who receive a high ureter dose as a result of needles being positioned in close proximity to the ureter.

Results from both studies demonstrate that IC/IS image-guided brachytherapy has a lower adverse side effect profile and that survival is improved.

"The increased, but targeted, radiation dose to the tumor controls the cancer better without adversely affecting nearby organs and tissues," Fokdal explained.

"Taking all of these results together, we have growing evidence in favor of IC/IS IGBT for treating cervical cancer," he concluded.

Reassuring Evidence

Commenting on the study, ESTRO President Yolande Lievens, MD, PhD, head of radiation oncology, Ghent University Hospital, Belgium, noted that results from EMBRACE and RetroEMBRACE provide "reassuring evidence" of the benefit of combining IC and IS brachytherapy to treat locally advanced cervical cancer.

"The study showed that patients who are at higher risk of complications can be identified, thus allowing us to monitor them more closely and maybe use a slightly different treatment approach to decrease their risk [for complications]," Lievens said in a statement.

"But the study also clearly illustrated that using the latest technology translates into better outcomes and value for our patients," she added.

The RetroEMBRACE study was funded by grants from Varian, Electra, and the Danish Cancer Society. The EMBRACE study was funded by Nucletron, an Elekta company, Varian Medical System, and the Danish Cancer Society. Dr Fokdal has disclosed no relevant financial relationships.

ESTRO37. Abstract OC-0072, presented April 21, 2018.

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