Our Experience of OSAKA Regimen (Bladder Preservation) in Patients with Advanced Bladder Cancer

Abstract

Introduction and Objectives

OSAKA regimen is a novel bladder preservation therapy involving balloon-occluded selective arterial infusion of radio-sensitizing chemotherapeutic agent with concurrent hemodialysis (HD), followed by radiation therapy. Objectives are to study the feasibility of this novel regimen in patients with advanced cancer bladder (Ca Bladder).

Methods

Two patients having advanced Ca Bladder with cisplatin ineligibility and poor performance status were managed with OSAKA regimen. Patients undergo super selective catheterisation of the anterior division of the internal iliac artery, followed by concurrent instillation of cisplatin (100 mg) via microcatheters and hemodialysis. Within 72 h, definitive radiation therapy is given. Image-guided radiation therapy (IGRT) with Helical Tomo using an Accuracy Radixact Tomography machine was used. 60 Gray/30 fractions is given to the bladder and nodes (50 Gray to bladder and nodes plus margin, with a boost of 10 Gray to bladder plus margin). Response is monitored by 3 monthly fluorodeoxyglucose positron emission tomography (FDG PET) imaging.

Results

Our first patient tolerated the procedure well and showed a complete response at 3 months of FDG PET imaging, but unfortunately, 1 year of FDG PET showed bony metastases, and the patient was managed accordingly. Our second patient also tolerated the regimen well, showed a complete response at 3 and 12 months of FDG PET imaging, and is under follow-up.

Conclusions

The OSAKA regimen, as a bladder preservation strategy, is feasible and safe in selective advanced Ca Bladder patients.

Introduction

OSAKA Medical College in Japan developed a novel bladder preservation therapy (OSAKA regimen) which involves balloon-occluded arterial infusion (BOAI) of an anticancer agent and concurrent hemodialysis which is then followed by radiation therapy. The OSAKA regimen comprised of a single bolus of cisplatin (100–300 mg ) delivered to the urinary bladder via vesical arteries using a balloon-occluded catheter. The patient undergoes hemodialysis after intraarterial chemotherapy allowing accumulation of cisplatin at the tumour site with minimal systemic toxicity followed by radiation [1]. We at our institution have tried this regimen in two of our patients with advanced bladder cancer who were unfit for surgery or chemotherapy. Delivering cisplatin to the bladder via balloon-occluded intra-arterial infusion, with simultaneous hemodialysis and a concurrent course of radiotherapy, offers a survival advantage over total cystectomy in some patients with invasive bladder cancer, so researchers from Japan, who have dubbed this combination therapy, the OSAKA regimen state that “95% of patients with locally advanced urothelial bladder cancer who were treated in this way achieved a complete response and did not develop any recurrent disease or metastasis” in a study published in the December issue of the American Journal of Clinical Oncology [2].

Methodology

The procedure is conducted in the Interventional Radiology room. First, both the internal iliac arteries were engaged with a cobra catheter, and microcatheters were placed super selectively into the anterior division of the internal iliac artery (Fig. 1). Fogarty catheter was used for occlusion as the balloon-occluded catheter used in the original OSAKA regimen was not available in India. Concurrent instillation of cisplatin (100 mg) via microcatheters was done. Dose estimation and guidance was given by our Medical Oncology and Nephrology teams. Dialysis was started simultaneously after inserting the right femoral tunnelled catheter unlike the original regimen where bilateral femoral tunnelled catheters were inserted. A single catheter was inserted due to a lack of equipments. The tip of the catheter is placed at the confluence of common iliac veins to minimise the entry of drug into the systemic circulation.

Fig. 1.

Bilateral internal iliac artery cannulation

Hemodialysis was done again for 4 h in the recovery room immediately after the procedure. The blood flow and dialysate flow were kept at 350 ml/min and 500 ml/min, respectively. As the molecular weight of protein unbound cisplatin is approximately 300, similar to that of creatinine, hemodialysis is efficient for cisplatin elimination. Additionally, the anatomical structure and blood supply of the bladder may largely account for the efficient drainage of cisplatin achieved with this approach [3]. Within 72 h, definitive radiation therapy was given by Helical Tomo using an Accuracy Radixact Tomography machine. 60 Gray/30 fractions is given to the bladder and nodes (50 Gray to bladder and nodes plus margin with a boost of 10 Gray to bladder plus margin). The response was then monitored by 3 monthly FDG PET imaging.

Results

In the original study conducted in Japan, a total of 329 patients (TisN0 16, T2N0 174, T3N0 77, T4N0 22, and TxN+ 40) were assigned to receive the OSAKA regimen. Patients who did not achieve complete response underwent total cystectomy or secondary balloon-occluded arterial infusion with an increased amount of cisplatin and/or gemcitabine. The OSAKA regimen allowed 83.6% (276 of 329) of patients in total and 93.6% (250 of 267) of patients with organ-confined disease (including T3b) to achieve complete response. Of patients with a complete response, 96% (240 of 250) survived with a functional bladder without evidence of recurrent disease within a mean follow-up of 159 weeks. Although lymph node involvement, especially the N2 stage, was selected as a significant risk factor for treatment failure and survival, it was noteworthy that 61.9% of patients with N1 disease achieved complete response and that the 5-year overall survival rate was 72.2%. No patients had grade III or more severe toxicities [3].

In our study, we got an opportunity to offer the OSAKA regimen to two of our patients with advanced bladder cancer. The results of both the patients are as follows:

First patient

This patient was a 73-year-old male gentleman who had hypertension (HTN) and chronic kidney disease (CKD) with creatinine of 6.19 mg/dl. He was on maintenance dialysis (twice a week). Also, he had type 2 diabetes mellitus (DM) and coronary artery disease (CAD) and was on ecospirin. Histopathology of this patient showed high-grade papillary urothelial cell carcinoma, stage T3bN1. FDG showed uptake in left external iliac nodes, focal pleural thickening noted along the posterior aspect of the apical segment of the right lung upper lobe, and uptake in the right peripheral zone of the prostate gland. OSAKA regimen was followed. FDG after 1 year showed complete response with no complaints, with improved quality of life with a quality of life score of 85. This patient was followed up for 4 years, and finally, he expired due to his ongoing CKD issues.

Second patient

The other patient was a 58-year-old male, hypertensive and a known case of Ca bladder with lymph node metastasis. Histopathology showed high-grade invasive urothelial carcinoma, stage T3bNx. The tumour was seen to infiltrate diffusely into the underlying muscle. The patient did not tolerate palliative chemotherapy and had passage of clots in urine with intermittent urinary obstruction with serum creatinine of 2.94 mg/dl for which clot evacuation was done and finally underwent bilateral percutaneous nephrostomies (PCN). FDG showed uptake in the diffuse sheet-like hemi-circumferential wall thickening in the left lateral wall of the urinary bladder involving UV junction (Figs. 2 and 3) superior rectal and mesorectal nodes, right juxtaphrenic node. OSAKA regimen was followed for this patient as well. Cystoscopy (post OSAKA) revealed that the bladder lesion size was smaller than the previous cystoscopy size. Three monthly and 6 monthly FDG PET showed complete response (Fig. 4). Taking the resolution into consideration, the patient underwent palliative cystectomy. Unfortunately, 1 year follow-up CT showed right adrenal gland metastases and skeletal metastases and suggested disease progression. This patient eventually expired but had a quality of life score of 95, after receiving the regimen and inoperable disease became an operable one in this patient.

Fig. 2.

Pre OSAKA scan

Fig. 3.

Pre OSAKA scan

Fig. 4.

CT scan after 6 months

Conclusions

We at our centre studied two patients with advanced Ca bladder, one with stage T3bN1 and the other with stage T3bNx, who were either ineligible for cisplatin chemotherapy or did not tolerate chemotherapy. Our study proves that this regimen can be offered to patients with advanced Ca bladder who are cisplatin ineligible or who cannot tolerate chemotherapy. Chemotherapy-related systemic side effects are drastically reduced as the chemotherapeutic agent is directly reaching the tumour. Also, it has an advantage of converting an inoperable disease into an operable one as seen in our second patient. OSAKA is better tolerated by the patients without much side effects. The OSAKA regimen, as a bladder preservation, is feasible and safe in selective advanced Ca bladder patients.

To conclude, the OSAKA regimen makes it possible to give chemotherapy for cisplatin-ineligible patients. It improves the quality of life of patients with advanced bladder cancers. It has an advantage of converting an inoperable disease into an operable one. OSAKA is better tolerated by the patients without much side effects, but there is a constant need to study this regimen in greater volumes in countries like India.

Declarations

Ethical Approval

Ethical clearance for the study has been obtained from the Ethical committee of our institution.

Consent to Participate

Written informed consent for publication of their clinical details and/or clinical images was obtained from the patient/parent/guardian/ relative of the patient. A copy of the consent form is available for review by the Editor of this journal.

Conflict of Interest

The authors declare no competing interests.

Patient Consent Form

Yes.

Guarantor

Not applicable.

Level of Evidence

3 (Expert opinions).