Prostate cancer (PCa) is the most common non-skin malignancy of men in developed countries. In spite of treatment with curative intent up to 30-40% of patients have disease recurrence after treatment, resulting from any combination of lymphatic, hematogenous, or contiguous local spread. The concept of early detection of PCa offer benefits in terms of reduced mortality, but at the cost of over-diagnosis and overtreatment of indolent disease. This is largely due to the random nature of conventional biopsies, with a risk of missing significant cancer and randomly hitting indolent disease. In the present thesis, diagnostic performance of MRI DWI and 11C Acetate PET/CT lymph node staging of intermediate and high risk PCa, was investigated, and additionally, predictive factors of regional lymph node metastases were evaluated. Further, additional value of targeted biopsies to conventional biopsies, for detection of clinically significant PCa, was investigated. In paper one and two, 53 and 40 patients with predominantly high risk PCa underwent 11C Acetate PET/CT and 3T MRI DWI, respectively, for lymph node staging, before extended pelvic lymph node dissection (ePLND). The sensitivity and specificity for PET/CT was 38% and 96% respectively. The sensitivity and specificity for MRI DWI was 55% and 90% respectively. In paper three, 53 patients with newly diagnosed PCa were included. All patients underwent multi-parametric MRI, followed by two cognitive targeted biopsies. Five more clinically significant cancers were detected by adding targeted biopsies to conventional biopsies. In paper four the value of quantitative and qualitative MRI DWI and 11C Acetate PET/CT parameters, alone and in combination, in predicting regional lymph node metastases were examined. ADCmean in lymph nodes and T-stage on MRI were independent predictors of lymph node metastases in multiple logistic regression analysis. In conclusion the specificity of diffusion weighted MRI and 11C Acetate PET/CT for lymph node staging was high, although the sensitivity was low. Predictive factors of regional lymph node metastases could be retrieved from diffusion weighted MRI and 11C Acetate PET/CT. By combining targeted biopsies with conventional biopsies the detection rate of clinically significant PCa could be increased.

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Systematic reviews on diagnostic test accuracy studies provide an overview of the current literature in a systematic and transparent manner. They are the highest level of evidence in clinical research, therefore they are critical to decision-making in the healthcare setting. Cancer is the primary source of mortality in Canada, however early detection of tumors can improve the survival rates and long-term health outcomes of patients. The primary method of cancer diagnosis is histopathological assessment, however, its use remains controversial. It is an invasive procedure and requires resources and clinical expertise not readily available. Noninvasive clinical imaging has been studied as a clinically desirable method for cancer diagnosis, however its diagnostic accuracy has yet to be established in the medical setting. With the increased role of DTA research in medicine, the current literature needs to be summarized in an effective way to properly educate and influence clinical decision-making. The objective of this thesis is to address the current evidence gaps in DTA research by conducting several systematic reviews to evaluate the accuracy of diagnostic methods in cancer-related imaging. The last chapter of the thesis will provide a critical reflection on the current landscape of DTA studies in cancer-related imaging, based on the findings of the reviews in the thesis.