Visceral disease in castration-resistant prostate cancer

Abstract

Metastatic involvement of the viscera in men with advanced castration-resistant prostate cancer (CRPC) has been poorly characterised to date. In 359 CRPC patients treated between June 2003 and December 2011, the frequency of radiologically detected visceral metastases before death was 32%. Of the 92 patients with computed tomography performed within 3 mo of death, 49% had visceral metastases. Visceral metastases most commonly involved the liver (20%) and lung (13%). Median survival from diagnosis of visceral disease was 7.1 mo (95% confidence interval, 5.9-8.3). Survival was affected by the degree of bone involvement at detection of visceral disease, varying from 6.1 mo in men with more than six bone metastases to 18.2 mo in men with no bone metastases (p=0.001). Heterogeneity was noted in clinical phenotypes and prostate-specific antigen trends at development of visceral metastases. Visceral metastases are now more commonly detected in men with CRPC, likely due to the introduction of novel survival-prolonging treatments.

Figure 1

Panel A: Prevalence of visceral and bone metastases over time. Panel B: Venn diagrams: Pattern of visceral, bone and nodal disease 3-6 months prior to death and 12-15 months prior to death. Panel C: Survival of men with CRPC and visceral metastases, separated by degree of bone involvement.

Figure 2. Discordance of PSA trend at development of visceral disease in two patients with molecular work-up.

Figure 2A: Log PSA trend and computed tomography (CT) images of a patient with a 100-fold PSA decline on docetaxel-based chemotherapy. Despite very low levels of PSA the patient developed metastatic liver disease. Biopsy revealed small cell carcinoma morphology and negative IHC staining for PSA and AR (Aperio Scanscope, magnification 10x for all images). Figure 2B: Patient developing widespread liver metastasis on treatment with abiraterone acetate in the presence of PSA stability. The archival primary prostate biopsy shows adenocarcinoma with positive IHC staining for PSA, AR and ERG and FISH confirming an underlying ERG rearrangement. At development of liver metastases in the absence of a rising PSA, a liver biopsy shows adenocarcinoma with negative IHC staining for PSA, AR and ERG despite an underlying ERG gene rearrangement (Aperio Scanscope, magnification 10x for H&E and IHC images, Ariol System for FISH pre-treatment image, magnification 40x; new liver metastasis magnification 20x)