A case of severe side effects to androgen receptor inhibitor and consequently switch to radioligand therapy in early castration resistant prostate cancer.

The development of potent novel androgen receptor inhibitors (ARi) such as apalutamide have improved the life expectancy in men with castration-resistant prostate cancer (CRPCa). However, some serious toxicity can occur limiting the choice of treatment in CRPCa. In our case, the patient experienced severe toxicity after initiation of apalutamide. Diagnostic PSMA-PET/CT confirmed the recurrence and tailored the treatment with 177Lu-PSMA-617 (RLT), a beta emitter radionuclide. RLT resulted in prolonged progression-free survival, thus postponing the commonly seen additional toxicity of chemotherapy. The case highlights the possibility of early RLT in PSMA avid tumors, a treatment with minimal side-effects.

Systemic interrogation of immune-oncology-related proteins in patients with locally advanced prostate cancer undergoing androgen deprivation and intensity-modulated radiotherapy.

PURPOSE: The primary objective was to establish whether blood-based leucine-rich alpha-2-glycoprotein (LRG1) can predict outcomes in patients with locally advanced prostate cancer undergoing androgen-deprivation therapy (ADT) and radiotherapy (RT) and to determine how it may relate to 92 immune-oncology (I-O)-related proteins in this setting. METHODS: Baseline blood level of LRG1 from patients treated with ADT and RT enrolled in the CuPCa (n = 128) and IMRT (n = 81) studies was measured using ELISA. A longitudinal cohort with matched blood samples from start of ADT, start of RT, and end of RT protocol from 47 patients from the IMRT cohort was used to establish levels of I-O proteins by high-multiplexing Proximal Extension Assay by Olink Proteomics. Statistical analyses using Kaplan-Meier, Cox regression, and LIMMA analyses were applied to predict the prognostic value of LRG1 and its correlation to I-O proteins. RESULTS: High baseline levels of LRG1 predicted a low frequency of treatment failure in patients undergoing ADT + RT in both the CuPCa and the IMRT cohorts. LRG1 was moderately correlated with CD4, IL6, and CSF1. We identified I-O proteins predicting metastatic failure (MF) at different timepoints. CONCLUSION: LRG1 biomarker is associated with I-O proteins and can be used to improve stratification and monitoring of prostate cancer patients undergoing ADT + RT. This work will require further in-depth analyses in independent cohorts with treatment outcome data.

Acute and long-term toxicity in primary hypofractionated external photon radiation therapy in patients with localized prostate cancer.

BACKGROUND: Compelling evidence exists for the iso-effectiveness and safety of moderate hypofractionated radiotherapy (Hypo-RT) schedules [1, 2]. However, international guidelines are not congruent regarding recommendation of ultrahypofractionated radiotherapy (UHF-RT) to all risk groups. METHODS: The current review gives an overview of clinically relevant toxicity extracted from major randomized controlled trials (RCT) trials comparing conventional to hypofractionated regimes in the primary setting of external photon radiation. Functional impairments are reported by using physician-rated and patient-reported scores using validated questionnaires. RESULTS: The uncertain radiobiology of the urethra/bladder when applying extreme hypofractionation may have contributed to worse acute urinary toxicity score in the Scandinavian UHF-RT and worse subacute toxicity in PACE-B. The observed trend of increased acute GI toxicity in several moderate Hypo-RT trials and one UHF-RT trial, the Scandinavian Hypo-RT PC trial, could be associated to the different planning margins and radiation dose schedules. CONCLUSION: Nevertheless, Hypo-RT has gained ground for patients with localized PCa and further improvements may be achieved by inclusion of genetically assessed radiation sensitivity. Several RCTs in Hypo-RT have shown non-inferior outcome and well-tolerated treatment toxicity by physician-rated scores. In the future, we suggest that toxicity should be measured by patient-reported outcome (PRO) using comparable questionnaires.