Branched peptides as novel tumor-targeting agents for bladder cancer.

Bladder cancer (BC) ranks ninth in world¬wide cancer incidence. It is the seventh most common cancer in men and the 17th most common cancer in women, with more than 330,000 new cases and more than 130,000 deaths each year [1]. Globally, the incidence of BC varies significantly, with Egypt, western Europe and North America having the highest incidence rates, and Asian countries the lowest rates [1]. There will be approximately over 70,000 new cases of BC and over 14,000 deaths in the USA in 2011, where BC remains the fifth leading new cancer diagnosis and is fourth among men [2]. According to the Italian Association of Medical Oncology–Italian Association of Cancer Registries data, in Italy, 24,000 men and 4000 women were diagnosed with BC in 2011, and it is esti¬mated that over 30,000 and over 34,000 BC diagnoses will occur in 2020 and in 2030, respectively [3]. The main clinical impact of BC is related to recurrence and progression of disease. Patients with BC have the highest lifetime treatment costs per patient among all cancers, due to the numerous retreatments for recurrence requiring a further transurethral resection and for progression of the disease requiring a radical cystectomy [4]. Up to 80% of BCs are non-muscle-invasive BC (NMIBC); however, as many as 70% of these NMIBCs may recur and up to 25% of patients will progress to invasive disease [1,5]. NMIBC represents a heterogeneous disease where the risks of both recurrence and progression may be estimated for individual patients using scoring systems and risk tables. To predict separately the short- and long-term risks of both recurrence and progression in individual patients, a scoring system and risk tables were developed by the European Organisation for Research and Treatment of Cancer [6]. The stratification of patients into low-, intermediate- and high-risk groups separately for recurrence and pro¬gression is pivotal to recommending further treatments [4]. Patients diagnosed with BC may suffer several recurrences during their lives, and a significant percentage of these recurrences are probably undetected tumors at white light cystoscopy, which were not initially resected, rather than true recur¬rent new lesions [4,7]. Consequently, there is a great need for improving the diagnostic accuracy of our technologies. Porphyrin-induced fluorescence cystoscopy (photodynamic diagnosis) that uses photoactive porphyrins, such as hexylaminolevulinate or 5-aminolevulinic acid, which accumulate preferentially in neoplas¬tic tissue and emit red fluorescence under blue light (blue light cystoscopy), has been reported to improve the diagnostic accu¬racy of conventional cystoscopy for detect¬ing bladder tumors, particularly carcinoma in situ. The additional detection rate of photodynamic diagnosis was 20% for all tumors and 23% for carcinoma in situ in a cumulative analysis of prospective trials [7].