Balloon-Occluded Chemo for Bladder Cancer Shows Nerve-Sparing Blood Flow Patterns

A technique designed to deliver chemotherapy directly to bladder tumors while sparing nearby nerves appears to work partly by redirecting pelvic blood flow, according to a new analysis published in CVIR Oncology. Researchers studying double balloon-occluded arterial infusion (D-BOAI) chemotherapy found that the procedure consistently blocked contrast flow into the superior gluteal artery and produced reversed flow in the inferior gluteal artery in nearly nine out of ten treated sides, patterns the authors say may help explain why severe neurological complications are rarely reported with the technique.

D-BOAI is a component of a bladder-preserving treatment protocol developed at the authors’ institution by Azuma and colleagues, which combines transurethral resection of bladder tumors, systemic chemotherapy, radiation therapy, hemodialysis, and arterial infusion facilitated by a four-lumen double-balloon catheter. During the procedure, the proximal balloon is positioned in the internal iliac artery just above the origin of the superior gluteal artery, while the distal balloon sits at the superior gluteal artery’s origin. This arrangement isolates the anterior trunk of the internal iliac artery, placing the targeted vesical arteries between the two balloons so that anticancer drugs, infused bilaterally through side holes between the balloons, are directed toward the bladder.

The concern motivating the study is well established in interventional oncology. Castellanos and colleagues reported that anticancer drug inflow during intrapelvic or extrapelvic infusion can cause neurological complications, most likely through chemotherapy-induced small vessel injury leading to plexus or nerve infarction, although a direct neurotoxic effect of cisplatin cannot be excluded. The nerves supplying the buttocks and lower extremities depend on the arteries at issue: the superior gluteal nerve is supplied by the superior gluteal artery, while the inferior gluteal nerve and sciatic nerve are supplied by the inferior gluteal artery. Infusing chemotherapy into either artery could therefore injure these nerves. Yet Azuma and colleagues previously reported no Grade 3 or higher neurological complications in the buttocks or lower extremities during D-BOAI, and the reason for this safety record remained unclear.

To investigate, the team analyzed digital subtraction angiography images acquired with all four balloons of the bilateral catheters fully inflated, immediately before drug infusion. The study included one hundred sides from fifty patients treated between November 2013 and September 2014, drawn as a secondary analysis of a previously reported cohort. Eligible patients had histologically confirmed carcinoma in situ or stage T1 through T4 muscle-invasive bladder cancer without distant metastasis; the study also included patients with non-invasive bladder cancer who chose D-BOAI after thorough counseling. Patients younger than 20 years were excluded, and no additional inclusion or exclusion criteria were applied beyond those of the original cohort.

Two interventional radiologists with 15 and 37 years of experience independently classified blood flow in the inferior gluteal artery into three types. Type 1 was anterograde flow, with contrast medium disappearing anterogradely in the main trunk or branches. Type 2 was weak reversed flow, in which contrast entered the peripheral vessels and, after opacifying the entire vessel, disappeared in a retrograde fashion. Type 3 was strong reversed flow, in which marked retrograde flow prevented contrast from entering the vessel at all, so the entire vessel could not be visualized. Superior gluteal artery flow was simply classified as confirmed or not confirmed owing to distal balloon occlusion. In all cases, pelvic aortic angiography beforehand confirmed anterograde flow in both arteries.

The results were striking. No inflow of contrast medium into the superior gluteal artery was observed in any of the 100 sides, indicating that the distal balloon reliably blocked flow into that vessel. In the inferior gluteal artery, anterograde Type 1 flow occurred in only 11 percent of sides, while weak reversed Type 2 flow appeared in 45 percent and strong reversed Type 3 flow in 44 percent. Interobserver agreement for the three-type classification was substantial, with a weighted kappa coefficient of 0.79, and discrepancies were resolved by consensus.

On the safety side, none of the 50 patients experienced Grade 2 or more severe neurological complications in the buttocks or lower extremities, as assessed by the National Cancer Institute’s Common Terminology Criteria for Adverse Events v6.0 during the week following treatment. Three patients did develop Grade 1 neuralgia. One developed right lower extremity neuralgia on the third day after treatment, persisting through the first week; that patient’s inferior gluteal artery flow pattern was Type 1. Another developed left buttock neuralgia on the fourth day, persisting through the first week, with a Type 3 pattern. A third developed neuralgia in both thighs on the fifth day, which resolved by the seventh day, with Type 3 flow on the right and Type 2 on the left. All three recovered with conservative management.

The authors interpret these hemodynamic patterns as a plausible mechanism for neurological safety. Because contrast flow into the superior gluteal artery was blocked in every case, anticancer drug inflow into that artery, and thus into the territory of the superior gluteal nerve, is unlikely. The high frequency of reversed flow in the inferior gluteal artery suggests that drug delivery into that vessel is also likely restricted, limiting exposure of the inferior gluteal and sciatic nerves. Blocking superior gluteal inflow may carry an additional therapeutic benefit: more of the infused drug can reach the bladder, the intended target. The team also notes that balloon-occluded techniques in hepatic interventions can reduce arterial pressure and induce collateral flow changes that alter drug distribution, supporting the plausibility of such hemodynamic modification.

Why reversed flow occurs so frequently in the inferior gluteal artery remains unresolved. The authors point to prior work showing that internal iliac artery pressure falls by a mean of 55.2 mmHg after balloon occlusion during D-BOAI, which may trigger compensatory hemodynamic changes. The inferior gluteal artery anastomoses with the superior gluteal, internal pudendal, obturator, and medial femoral circumflex arteries, and earlier pelvic angiography work in patients undergoing iliac artery ligation found that collateral circulation via the medial femoral circumflex artery became functional immediately after ligation. In D-BOAI, blood flow compensation to the inferior gluteal artery through these anastomoses may therefore manifest as the reversed flow observed on angiography.

The authors are careful to frame the findings as hypothesis-generating rather than proof of safety. The study was retrospective, single-institution, and small, limiting generalizability, and it carried potential selection bias as a secondary analysis of a previously reported cohort. Blood flow assessment by digital subtraction angiography was qualitative and subjective, not quantitative, and the infusion rate and pressure during angiography differ considerably from those of actual drug infusion, so actual blood flow was not accurately evaluated. The nerves in question may also receive blood from vessels other than the two arteries studied, drug distribution was not directly measured, nerve perfusion was not assessed, and the one-week observation window may have missed delayed neurological complications. The relationship between the observed hemodynamics and neurological safety therefore remains hypothetical, and quantitative hemodynamic measurements and objective image analysis will be needed to test the mechanism the study proposes.

Subject of Research: Extrapelvic blood flow patterns during double balloon-occluded arterial infusion chemotherapy for bladder cancer and their possible relationship to neurological safety

Article Title: Extrapelvic flow patterns during double balloon-occluded arterial infusion chemotherapy for bladder cancer: implications for neurological safety

Article References: Yamamoto, K., Yamamoto, K., Juri, H., Azuma, H., & Osuga, K. (2026). Extrapelvic flow patterns during double balloon-occluded arterial infusion chemotherapy for bladder cancer: implications for neurological safety. CVIR Oncology, 2(1), Article 35. https://doi.org/10.1007/s44343-026-00067-x

Image Credits: AI Generated

DOI: 10.1007/s44343-026-00067-x

Keywords: bladder cancer, D-BOAI, arterial infusion chemotherapy, double-balloon catheter, superior gluteal artery, inferior gluteal artery, digital subtraction angiography, neurological complications, pelvic hemodynamics, interventional radiology, bladder preservation, cisplatin