Page 14 - Towards personalized therapy for metastatic prostate cancer: technical validation of [18F]fluoromethylcholine

Chapter 1
Prostate cancer
Prostate cancer (PC) is the second most common cancer in men worldwide [1]. The disease presents itself mostly in men above the age of 50 and the incidence increases with age. The clinical behavior of PC is very diverse. Some tumors are indolent, do not cause any symptoms and arise as microscopic, well-differentiated foci that may never become clinically manifest. However, a significant proportion of PC patients presents with or will develop aggressive tumors that lead to morbidity, metastases and ultimately to death. The estimated incidence of PC in Europe in 2012 was 417,000, with 92,000 death reported. [2]. Recurrence in patients with PC is common during the first decade after treatment with curative intent, including radical prostatectomy (RP), brachytherapy or external radiotherapy. Cancer specific survival (CSS) at 10-years follow-up after RP is 84-90%, while post external radiotherapy the CSS vary between 77-95% [3].
The initial systemic treatment in metastatic PC is based on androgen deprivation. Nevertheless, after an initial response to anti-hormonal therapy, the majority of PC patients will ultimately progress and reach a castration-resistant (CR) state. Progression towards castration-resistant prostate cancer (CRPC) is common within 18-36 months [3]. In these patients, chemotherapy has proven to slow down androgen independent tumor growth. In particular, docetaxel, a registered agent from the taxane class, was introduced as first-line chemotherapy [4]. Its effect is largely based on interaction with microtubules [5]. Docetaxel plus estramustine or prednisone was found to significantly reduce the prostate-specific antigen (PSA) value and improve overall survival when compared to mitoxantrone-prednisone therapy. In combination with prednisone, docetaxel also appeared to be useful in achieving significant improvement of pain palliation and quality of life [4, 6]. These clinical results have resulted in the regimen of docetaxel and prednisone once every three weeks becoming the current recognized standard chemotherapeutic treatment of CRPC [6].
Although these successes with docetaxel have improved clinical outcome of PC, the progressive development of chemotherapy resistance in PC remains a major
problem and new chemotherapeutic agents that circumvent resistance are urgently needed. Cabazitaxel is found to be such an agent, being accepted as the second-line cytotoxic modality in metastatic CRPC. Its role is based on the possibility of exerting antitumor activity on docetaxel-resistant neoplasms [7, 8]. Clinical studies, including
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