Bladder cancer

  • Worldwide, the number of new cases in 2018, both sexes, all ages is 549,393 and 199,922 deaths from bladder cancer 1
  • Organ-removing radical cystectomy (RC) is considered the standard of care in advanced disease and is associated with the risk for prolonged hospitalization and substantial morbidity, related to stoma care 3,5
  • RC and bladder-sparing tri-modality therapy (TMT) (radiation therapy, concurrent chemotherapy, and transurethral resection of bladder tumor) options are both recommended by guidelines and have similar survival but different morbidity and life quality profiles 3,4
  • Bladder-sparing treatment including localized radiation therapy achieves preservation of the bladder in over 70% of patients 3
  • TMT is an alternative to RC, especially in patients with a high operative risk or not willing to sacrifice their bladder 5

BioXmark® for bladder cancer radiation therapy

Radical chemoradiotherapy for patients with muscle-invasive bladder cancer is becoming accepted as a viable treatment option with good long-term outcomes. However, high dose radiation can damage normal tissue if not accurately targeted. Image guided radiotherapy aided by fiducial markers improves patient outcomes, on one hand by sparing small bowel and uninvolved bladder toxicity and on the other hand by increased actual dose of the tumor radiation. Traditional gold fiducial markers are safe and feasible to apply; 6,7 however, the procedure is time consuming and literature studies shows that up to 40% of the gold seeds are lost in verification imaging.8 A contrast agent Lipiodol, used as a fiducial marker, is also shown to be safe and feasible.9,10 However, the biggest disadvantage of Lipiodol is fading, poor visualization and loss of spots likely due to intravesical spillage during injection in the perivesical fatty tissue, leading to inaccurate delineation of the tumor borders. 9,11
BioXmark® has the potential benefit of stable visibility without blurring properties or spillage combined with simple application.

BioXmark® – Clinical study for use in bladder cancer IGRT

The study “BioXmark® liquid fiducial markers for image guided radiotherapy in bladder cancer, a safety and performance trial “is ongoing in Academic Medical Center, Amsterdam. The Principal investigator M.C.C.M. Hulshof, M.D., Ph.D., radiation oncologist. The study is registered in the Dutch Trial Register no NL 7396 (NTR 7605), date 18-07-2018. ABR number is NL 65305.018.18

BioXmark® implantation procedure used in the study:
Patients underwent a cystoscopy without sedation. A 23G needle was primed with the liquid marker before placement down the endoscope and the tip cleaned to remove eventual fluid at the outer contour of the needle. Once the tumor area was identified, the endoscopic needle was inserted in the endoscope system. Afterwards, volumes of 0.1 ml have been injected into the submucosal layer at the borders of the tumor, or at an endoscopic clearly defined near distance from the tumor. Preferably 4-5 sites of the tumor are marked, but at least 3. No learning curve was expected, as the injection of fluids with the aid of cystoscopy in the submucosa is considered a standard urological procedure.
The recruitment of all 20 study participants is completed. Results from the study will be presented when available.

For information about BioXmark®, see BioXmark®.


1. World Health Organization

2. The American Cancer Society

3. Royce T.J. et al. Comparative Effectiveness of Bladder-preserving Tri-modality Therapy Versus Radical Cystectomy for Muscle-invasive Bladder Cancer Clinical Genitourinary Cancer. 2019; Vol. 17, No. 1, 23-31

4. Kulkarni G. S. et al. Propensity Score Analysis of Radical Cystectomy Versus Bladder-Sparing Trimodal Therapy in the Setting of a Multidisciplinary Bladder Cancer Clinic. J Clin Oncol 2017; 35:2299-2305

5. Wettstein S.M. et al. Systematic review and meta-analysis on trimodal therapy versus radical cystectomy for muscle-invasive bladder cancer: Does the current quality of evidence justify definitive conclusions? PLoS ONE 2019; 14(4): e0216255

6. Biancia C. et al. Image guided radiation therapy for bladder cancer: Assessment of bladder motion using implanted fiducial markers. Pract Radiat Oncol 2014;4(2):108–15.

7. Garcia M. et al. Endoscopic gold fiducial marker placement into the bladder wall to optimize radiotherapy targeting for bladder-preserving management of muscle-invasive bladder cancer: Feasibility and initial outcomes. PLoS One 2014; 9: e89754.

8. Hulshof MC et al. Intravesical markers for delineation of target volume during external focal irradiation of bladder carcinomas. Radiother Oncol. 2007; 84(1):49-51.

9. Søndergaard J. et al. A study of image-guided radiotherapy of bladder cancer based on Lipiodol injection in the bladder wall. Acta Oncol 2010; 49:1109–15.

10. Chai X. et al. Behavior of Lipiodol Markers During Image Guided Radiotherapy of Bladder Cancer. Int J Radiat Oncol Biol Phys 2010; 77:309–14.

11. Nolan C.P. & Forde E.J. A review of the use of fiducial markers for image-guided bladder radiotherapy.
Acta Oncologica, 2016; 55:5, 533-538.