Circulating tumor cells and survival in abiraterone- and enzalutamide-treated patients with castration-resistant prostate cancer.

BACKGROUND: The outcome to treatment administered to patients with metastatic castration-resistant prostate cancer (mCRPC) greatly differs between individuals, underlining the need for biomarkers guiding treatment decision making. OBJECTIVE: To investigate the prognostic value of circulating tumor cell (CTC) enumeration and dynamics, in the context of second-line endocrine therapies (ie, abiraterone acetate or enzalutamide), irrespective of prior systemic therapies. DESIGN, SETTINGS, AND PARTICIPANTS: In a prospective, multicentre study blood samples for CTC enumeration were collected from patients with mCRPC at baseline (n = 174). In patients who responded for minimally 10-12 weeks a follow-up sample was collected. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: For baseline analysis, patients were stratified in <5 or ≥5 CTCs/7.5 mL, whereas for the analysis of CTC dynamics at 10-12 weeks, in patients with stable, increasing or decreasing CTC counts. Progression-free survival (PFS), overall survival (OS), and PSA changes at 10-12 weeks were compared between groups. RESULTS: Patients demonstrating increasing CTCs on therapy had a shorter median PFS (4.03 vs 12.98 vs 13.67 months, HR 3.6, 95%CI 1.9-6.8; P < 0.0001) and OS (11.2 months vs not reached, HR 9.5, 95%CI 3.7-24; P < 0.0001), compared to patients with decreasing or stable CTCs. Multivariable Cox regression showed that prior chemotherapy (HR 4.1, 95%CI 1.9-8.9; P = 0.0003), a high baseline CTC count (HR 1.5, 95%CI 1.2-1.9; P = 0.002) and increasing CTCs at follow-up (HR 3.3, 95%CI 1.4-7.6; P = 0.005) were independent predictors of worse PFS. Previous chemotherapy (HR 7, 95%CI 1.9-25; P = 0.003), high baseline CTC counts (HR 2.2, 95%CI 1.4-3.7; P = 0.002) and increasing CTCs during therapy (HR 4.6, 95%CI 1.4-15; P = 0.01) were independently associated with shorter OS. ≥30% and ≥50% PSA responses less frequently occurred in patients with CTC inclines at 10-12 weeks on therapy (χ2 test: P < 0.01). CONCLUSIONS: CTC dynamics during therapy are associated with PSA response and provide independent clinical prognostication over PSA declines. Hence the study demonstrates the pharmacodynamic properties of CTCs.

Recurrent reactive infectious mucocutaneous eruption in a male adult patient associated with Mycoplasma pneumoniae, SARS-CoV-2 and rhinovirus.

We present a case of a man in his early 30s who developed four episodes of reactive infectious mucocutaneous eruption (RIME), in association with different infectious pathogens.RIME is a recently implemented term to describe mucocutaneous eruptions associated with respiratory pathogens. These eruptions are characterised by predominant mucosal involvement of two or more mucous membranes and limited cutaneous involvement. The disease course and prognosis are mostly favourable, especially in recurrent episodes of RIME in the same patient. In recurrent episodes of RIME, Mycoplasma pneumoniae is often identified as the infectious trigger in the first episode.

Extra-anogenital giant cutaneous squamous cell carcinomas require multidisciplinary management.

Cutaneous squamous cell carcinoma (cSCC) is a highly prevalent cancer and the majority of cSCC have a good prognosis. However, a subset of cSCC can progress to advanced disease. We present the first reported case of a giant cSCC located on the breast. In addition, a systematic literature search on extra-anogenital giant (EAG) cSCC was performed using Pubmed and MEDLINE databases. Thirty-one articles could be retained which were relevant for this review. A total of 42 well-described cases were identified. Median age at presentation was 70 years (range 9-100 years). Twenty-four (57%) patients were male, eighteen were female (43%). The estimated median delay of treatment was 12 months (range 1 to >240 months). In 27 patients (64%) the giant cSCC was localized on the neck, face or scalp, 6 on the thoracic wall or back (14%), 4 on the lower limb (10%), 2 on the hip or buttock (5%), 2 on the upper limb (5%), one (2%) on the breast. Tumor stage at presentation was T2, T3 and T4 in respectively 26 (62%), 11 (26%) and 5 (12%) cases. Lymph node metastases were identified in 1 patient (2%) and distant metastases in another patient (2%). In 34 out of 42 cases (81%) primary radical surgical excision was performed, 3 received radiotherapy, 2 chemotherapy and 3 palliative care. In the cases with reported follow-up, four patients (4/30: 13%) died of disease. The treatment of EAG cSCC poses many problems, making a multidisciplinary approach of paramount importance.

TP53 Outperforms Other Androgen Receptor Biomarkers to Predict Abiraterone or Enzalutamide Outcome in Metastatic Castration-Resistant Prostate Cancer.

PURPOSE: To infer the prognostic value of simultaneous androgen receptor (AR) and TP53 profiling in liquid biopsies from patients with metastatic castration-resistant prostate cancer (mCRPC) starting a new line of AR signaling inhibitors (ARSi).Experimental Design: Between March 2014 and April 2017, we recruited patients with mCRPC (n = 168) prior to ARSi in a cohort study encompassing 10 European centers. Blood samples were collected for comprehensive profiling of CellSearch-enriched circulating tumor cells (CTC) and circulating tumor DNA (ctDNA). Targeted CTC RNA sequencing (RNA-seq) allowed the detection of eight AR splice variants (ARV). Low-pass whole-genome and targeted gene-body sequencing of AR and TP53 was applied to identify amplifications, loss of heterozygosity, mutations, and structural rearrangements in ctDNA. Clinical or radiologic progression-free survival (PFS) was estimated by Kaplan-Meier analysis, and independent associations were determined using multivariable Cox regression models. RESULTS: Overall, no single AR perturbation remained associated with adverse prognosis after multivariable analysis. Instead, tumor burden estimates (CTC counts, ctDNA fraction, and visceral metastases) were significantly associated with PFS. TP53 inactivation harbored independent prognostic value [HR 1.88; 95% confidence interval (CI), 1.18-3.00; P = 0.008], and outperformed ARV expression and detection of genomic AR alterations. Using Cox coefficient analysis of clinical parameters and TP53 status, we identified three prognostic groups with differing PFS estimates (median, 14.7 vs. 7.51 vs. 2.62 months; P < 0.0001), which was validated in an independent mCRPC cohort (n = 202) starting first-line ARSi (median, 14.3 vs. 6.39 vs. 2.23 months; P < 0.0001). CONCLUSIONS: In an all-comer cohort, tumor burden estimates and TP53 outperform any AR perturbation to infer prognosis.See related commentary by Rebello et al., p. 1699.