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Prostate cancer (PC) is the second most common cancer in men worldwide, affecting ~12%. Although most are clinically insignificant low-risk cancers, the more aggressive high-risk cancers require correct staging, prior to curative radiotherapy or surgery. Standard staging procedures and tools include clinical examination, estimated nomogram risk of pelvic lymph node (LN) metastases, and bone scintigraphy (BS). Additional staging information can be obtained with magnetic resonance imaging (MRI), computed tomography (CT) and positron-emission tomography/computed tomography (PET/CT). PET/CT can provide information on both functional and morphological changes.

The aims of the present thesis were to investigate the diagnostic and prognostic value of ¹¹C-acetate (ACE)-PET/CT in high-risk PC, and to optimize the ACE-PET protocol. In study I and II, higher detection rates of LN metastases and bone metastases were found with ACE-PET/CT, than with standard methods nomogram risk and BS. The higher ACE uptake in the prostate (prostate lipogenic tumor burden), the higher the risk of suspected LN metastases (N+ disease) on PET/CT. ACE-PET/CT findings correlated better than BS with follow-up data, and influenced therapy in 11-43%. In study III, PET reconstruction algorithm with resolution recovery showed more accurate functional tumor volumes compared to CT, and higher measurements of lipogenic activity, than reconstruction algorithm without resolution recovery. Study IV was part of an interventional radiotherapy study (PARAPLY) on high-risk PC, with addition of image-guided simultaneous integrated boost to delineated prostate tumors and pelvic LN metastases reported in ACE-PET/CT and MRI. Comparative analyses of clinical risk parameters and baseline ACE-PET/CT parameters showed significant associations between nomogram risk and prostate lipogenic tumor burden, between N+ disease on PET/CT and prostate lipogenic tumor burden, but surprisingly not between nomogram risk and N+ disease on PET/CT. PET with resolution recovery was superior in detection of N+ disease.

In conclusion, ACE-PET/CT showed a higher detection rate of suspected metastases compared to standard methods clinical nomogram and BS, in high-risk PC. PET reconstruction with resolution recovery seems to improve the diagnostic added value of ACE-PET/CT. Prostate lipogenic tumor burden could serve as a predictor of N+ disease. The prognostic value of ACE-PET/CT remains to be investigated in future studies.