Spicing up prostate cancer theranostics

Abstract

Chapter 1 (general introduction) provides an overview the development of radioactive labelled ligands being suitable for imaging and therapy of prostate cancer.

PART I: PROSTATE CANCER IMAGING Chapter 2 presents the results of a prospective validation study aiming to define diagnostic value of [68Ga]Ga-PSMA PET/CT in newly diagnosed prostate cancer patients. [68Ga]Ga-PSMA PET/CT detects lymph node metastases with high specificity (90.9%) and moderate sensitivity (41.5%). Although a negative [68Ga]Ga-PSMA PET/CT cannot rule out the presence of lymph node metastases, [68Ga]Ga-PSMA PET/CT may guide future patient selection.

In chapter 3, interobserver agreement in [68Ga]Ga-PSMA PET/CT reporting is determined. Classification with a standardized 5-point scale provides substantial interobserver agreement in localizing tumor sites in the prostate region (κ = 0.67), regional lymph nodes (κ = 0.62) and osseous structures (κ = 0.62). Structured reporting according to this method may be used to optimize [68Ga]Ga-PSMA PET/CT interpretation.

In chapter 4, a retrospective study is presented, assessing diagnostic performance of [18F]F-DCFPyL PET/CT compared to [68Ga]Ga-PSMA PET/ CT. Overall detection rate of [68Ga]Ga-PSMA PET/CT and [18F]F-DCFPyL PET/CT was respectively 73.8% and 72.4% (p = 0.85). Our data suggest that the diagnostic performance of both radiotracers in the setting of biochemical recurrence of prostate cancer post-prostatectomy is comparable.

PART II: PROSTATE CANCER THERAPY Chapter 5 describes the first patient with advanced prostate cancer, who underwent [177Lu]Lu-PSMA-617 therapy in the UMC Utrecht. A brief overview of the published literature on this specific subject is presented.

Thirty patients with advanced prostate cancer receiving 1-6 therapy cycles with 6 GBq [177Lu]Lu-PSMA-617 are studied in chapter 6. During treatment, maximum PSA decrease was ≥50% in 57% of the patients. Despite CTCAE-grade III and IV anemia occurring in two patients (7%), all other newly originated biochemical toxicity was limited to maximum CTCAE grade I-II. Grade II xerostomia occurred in 17% of the patients. These results confirmed the favorable safety and efficacy profile of [177Lu]Lu-PSMA-617.

In chapter 7, a 54-year old patient with metastatic castration resistant prostate cancer is described, in which [177Lu]Lu-PSMA therapy possibly led to severe bilateral papilledema causing visual deficit. The anticipated causes for this presentation are discussed.

In chapter 8, the impact of external cooling with icepacks on PSMA uptake in salivary glands was studied. When comparing radiotracer uptake in the intervention group to the control group, significant differences were found with regard to radiotracer uptake in the left parotid gland. These results indicate that impact of icepacks on PSMA uptake seems to be limited to the parotid glands. However, clinical relevance of these findings is debatable.

In chapter 9, toxicity profiles of 6.0 and 7.4 GBq [177Lu]Lu-PSMA therapy per cycle were compared. In the 6.0 GBq and 7.4 GBq group, CTCAE-grade 1-2 xerostomia occurred in respectively 13% and 20% and grade 3 anemia occurred in respectively 20% and 27% of the patients. One patient in the 7.4 GBq group (7%) had grade 3 thrombocytopenia. All other newly originated toxicities were limited to maximum grade 2. No significant differences were found, indicating that both activities are well-tolerated.