Studies on the pathogenesis and management of prostate carcinoma in dogs

Abstract

The dog is one of the few species to develop spontaneous prostate carcinoma (PCA) and is thus an attractive model for the study of the disease in humans. Many of the features of the disease in the dog are similar to its human counterpart, however a number of aspects of the pathogenesis, diagnosis and management of the disease are different between dogs and people. The first aim of the thesis was to investigate aspects of the pathogenesis of PCA in dogs. This thesis presents some similarities and some differences between dogs and humans in the pathogenesis of PCA. The expression of COX-2 is not related to inflammation or to the degree of differentiation in canine PCA as it is in humans. However, similar to human PCA, androgen ablation is associated with increased inflammation in the neoplastic tissue. Like humans, dogs with PCA have a shorter CAG-I repeat in the AR gene, but variations in length are much smaller than in humans. Differences in CAG repeat length and plasma androgens that may explain ethnic differences in the prevalence of PCA in humans cannot explain the predisposition of the Bouvier des Flandres to develop PCA. There is growing evidence of a potential protective effect of androgens in the development of PCA in dogs. The second aim of this thesis was to develop therapeutic tools for the management of PCA in dogs. Treatment of canine PCA remains palliative as it is effective in relieving clinical signs but cannot offer a cure. This thesis introduces an effective surgical technique for short-term management of PCA in dogs, provided there is no urethral obstruction. Photodynamic therapy is a promising treatment modality for cancer in general and prostate carcinoma in particular, however technical improvements to allow more efficient and even administration of light to prostatic tissue are necessary to make it useful in the management of clinical cases. Additional research needs to be performed to develop new techniques to remove canine PCA without recurrence or detrimental side effects. Total prostatectomy techniques, while preserving continence in the dog, partial prostatectomy with effective adjunctive radio-, chemo- or immunotherapy, or local minimally invasive interventional techniques can be mentioned as examples.