Prostat Kanserinde Vasküler Hedefli Fotodinamik Tedavi
Özet
Fotodinamik tedavi (FDT), belirli bir dalga boyundaki lazer ışığıyla doku içindeki ışığa duyarlılaştırıcının aktive edilerek hedeflenen dokunun yok edilmesini sağlayan minimal invaziv bir ablasyon yöntemidir. Son yıllarda görüntüleme yöntemlerindeki ilerlemeler ve radikal tedavilerin yan etkileri, prostat kanserinde fokal FDT uygulamalarına olan ilgiyi artırmıştır. Klasik hücresel hedefli fotokemoterapideki zayıf seçicilik ve çevre doku hasarı gibi sınırlılıkları aşmak adına, vasküler hedefli fotodinamik tedavi (VHF) geliştirilmiştir. Bu yöntemde padoporfin ve padeliporfin gibi ajanlar kullanılarak tümör mikrosirkülasyonunda geri dönüşü olmayan vasküler oklüzyon ve nekroz tetiklenir. VHF'nin en büyük avantajı termal olmaması, doku kollajen iskeletini ve üretral sfinkter gibi kritik yapıları koruyarak işlevsel zedelenmeleri minimuma indirmesidir. Klinik faz çalışmaları, bu fokal tedavinin düşük riskli ve radyoterapi sonrası nükseden prostat kanseri olgularında yüksek negatif biyopsi oranları sağladığını ve yan etki profili açısından son derece güvenli olduğunu göstermiştir.
Photodynamic therapy (PDT) is a minimally invasive ablation method that activates a photosensitizing agent using a specific laser wavelength to destroy targeted tissue. Advances in imaging and the functional side effects of radical treatments have driven interest in focal PDT for prostate cancer. To overcome the limitations of cellular-targeted photochemotherapy, such as poor selectivity and collateral tissue damage, vascular-targeted photodynamic therapy (VTP) was developed. Utilizing agents like padoporfin and padeliporfin, VTP triggers irreversible vascular occlusion and necrosis strictly within the tumor microcirculation. A key advantage of VTP is its non-thermal mechanism, which preserves the tissue collagen skeleton and critical surrounding structures like the urethral sphincter, thereby minimizing functional impairment. Clinical phase studies demonstrate that this focal approach achieves high negative biopsy rates and presents a highly tolerable safety profile for both low-risk localized prostate cancer and cases with recurrence after radiotherapy.
Referanslar
dos Santos AF, De Almeida DR Q, Terra LF, et al. Photodynamic therapy in cancer treatment—An update review. J. Cancer Metastasis Treat. 2019;5:25.
Nogueira L, Tracey AT, Alvim R, et al. Developments in Vascular-Targeted Photodynamic Therapy for Urologic Malignancies. Molecules. 2020;25:5417.
Davidson SRH, Weersink R, Haider MA, et al. Treatment planning and dose analysis for interstitial photodynamic therapy of prostate cancer. Phys. Med. Biol. 2009;54:2293–313.
Bugaj, A.M. Vascular targeted photochemotherapy using padoporfin and padeliporfin as a method of the focal treatment of localised prostate cancer—Clinician’s insight. World J. Methodol. 2016;6:65–76.
Nogueira L, Wang L, Fine SW, et al. Focal treatment or observation of prostate cancer: Pretreatment accuracy of transrectal ultrasound biopsy and T2-weighted MRI. Urology 2010;75:472–7.
Bedi N, Reddy D, Ahmed HU. Targeting the cancer lesion, not the whole prostate. Transl. Androl. Urol. 2020;9:1518–25.
Eymerit-Morin C, Zidane M, Lebdai S, et al. Histopathology of prostate tissue after vascular-targeted photodynamic therapy for localized prostate cancer. Virchows Archiv. 2013;463:547–52.
Madar-Balakirski N, Tempel-Brami C, Kalchenko V ve ark. Permanent occlusion of feeding arteries and draining veins in solid mouse tumors by vascular targeted photodynamic therapy (VTP) with Tookad. PLoS ONE 2010;5:e10282.
Kimm SY, Tarin TV, Monette S, et al. Nonthermal Ablation by Using Intravascular Oxygen Radical Generation with WST11: Dynamic Tissue Effects and Implications for Focal Therapy. Radiology 2016;281:109–18.
Muller BG, Fütterer JJ, Gupta RT, et al. The role of magnetic resonance imaging (MRI) in focal therapy for prostate cancer: Recommendations from a consensus panel. BJU Int. 2014;113:218–27.
Alvim R, Nagar K, Das S, et al. Positron Emission Tomography/Computed Tomography with Gallium-68-labeled Prostate-specific Membrane Antigen Detects Relapse After Vascular-targeted Photodynamic Therapy in a Prostate Cancer Model. Eur Urol Focus. 2021;7:472-8.
Preise D, Oren R, Glinert I, et al. Systemic antitumor protection by vascular-targeted photodynamic therapy involves cellular and humoral immunity. Cancer Immunol. Immunother. 2008;58:71–84.
Weersink RA, Forbes J, Bisland S, et al. Assessment of cutaneous photosensitivity of TOOKAD (WST09) in preclinical animal models and in patients. Photochem. Photobiol. 2005;81:106.
Trachtenberg J, Bogaards A, Weersink, et al. Vascular Targeted Photodynamic Therapy With Palladium-Bacteriopheophorbide Photosensitizer for Recurrent Prostate Cancer Following Definitive Radiation Therapy: Assessment of Safety and Treatment Response. J Urol 2007;178:1974-9.
Gertner MR, Bogaards A, Weersink RA, et al. 839 Initial results of a phase I II trial of WST09-mediated photodynamic therapy (WST09-PDT) for recurrent prostate cancer following failed external beam radiation therapy (EBRT). Eur. Urol. Suppl. 2004;3:212.
Azzouzi AR, Barret E, Bennet J, et al. TOOKAD® Soluble focal therapy: Pooled analysis of three phase II studies assessing the minimally invasive ablation of localized prostate cancer. World J. Urol. 2015;33:945–53.
Noweski A, Roosen A, Lebdai S, et al. Medium-term Follow-up of Vascular-targeted Photodynamic Therapy of Localized Prostate Cancer Using TOOKAD Soluble WST-11 (Phase II Trials). Eur. Urol. Focus 2019;5:1022–8.
Trachtenberg J, Weersink R, Davidson SR, et al. Vascular-targeted photodynamic therapy (padoporfin, WST09) for recurrent prostate cancer after failure of external beam radiotherapy: A study of escalating light doses. BJU Int. 2008;102:556–62.
Azzouzi AR, Barret E, Moore CM, et al. TOOKAD®Soluble vascular-targeted photodynamic (VTP) therapy: Determination of optimal treatment conditions and assessment of effects in patients with localised prostate cancer. BJU Int. 2013;112:766–74.
Moore CM, Azzouzi AR, Barret E, et al. Determination of optimal drug dose and light dose index to achieve minimally invasive focal ablation of localised prostate cancer using WST11-vascular-targeted photodynamic (VTP) therapy. BJU Int. 2015;116:888–96.
Azzouzi AR, Vincendeau S, Barret E, et al. Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): An open-label, phase 3, randomised controlled trial. Lancet Oncol. 2017;18:181-91.
