Abstract
BackgroundThere is a need to improve the treatment of prostate cancer (PCa) and reduce treatment side effects. Vascular-targeted photodynamic therapy (VTP) is a focal therapy for low-risk low-volume localised PCa, which rapidly disrupts targeted tumour vessels. There is interest in expanding the use of VTP to higher-risk disease. Tumour vasculature is characterised by vessel immaturity, increased permeability, aberrant branching and inefficient flow. FRT alters the tumour microenvironment and promotes transient ‘vascular normalisation’. We hypothesised that multimodality therapy combining fractionated radiotherapy (FRT) and VTP could improve PCa tumour control compared against monotherapy with FRT or VTP.MethodsWe investigated whether sequential delivery of FRT followed by VTP 7 days later improves flank TRAMP-C1 PCa tumour allograft control compared to monotherapy with FRT or VTP.ResultsFRT induced ‘vascular normalisation’ changes in PCa flank tumour allografts, improving vascular function as demonstrated using dynamic contrast-enhanced magnetic resonance imaging. FRT followed by VTP significantly delayed tumour growth in flank PCa allograft pre-clinical models, compared with monotherapy with FRT or VTP, and improved overall survival.ConclusionCombining FRT and VTP may be a promising multimodal approach in PCa therapy. This provides proof-of-concept for this multimodality treatment to inform early phase clinical trials.
Highlights
There is a need to improve the treatment of prostate cancer (PCa) and reduce treatment side effects
Vasculartargeted photodynamic therapy (VTP) monotherapy induces delayed tumour growth in prostate cancer flank tumour allografts We have previously reported antitumour effects of fractionated radiotherapy (FRT) in a syngeneic immunocompetent TRAMP-C1 PCa flank tumour allograft model.[26]
To investigate antitumour effects of VTP in this model and subsequently combine FRT and VTP as multimodality therapy, we developed an enclosed optical irradiation system to deliver VTP to flank allograft tumours (Supplementary Fig. 1)
Summary
There is a need to improve the treatment of prostate cancer (PCa) and reduce treatment side effects. We hypothesised that multimodality therapy combining fractionated radiotherapy (FRT) and VTP could improve PCa tumour control compared against monotherapy with FRT or VTP. CONCLUSION: Combining FRT and VTP may be a promising multimodal approach in PCa therapy. Vascular-targeted photodynamic therapy (VTP) is a novel minimally invasive focal ablation surgical procedure, achieved by rapid free radical-mediated destruction of tumour vasculature.[13,14,15,16] VTP is effective in focal ablation of low-risk low-volume PCa,[17,18,19] and has been investigated as salvage therapy for radio-recurrent PCa.[20,21] Despite interest in the use of focal ablation therapies such as VTP in higher-risk PCa, to date VTP has not been combined with other treatments as a multimodality therapy approach to highrisk PCa
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