Oligometastatic Squamous Cell Transformation From Metastatic Prostate Adenocarcinoma Treated With Systemic and Focal Therapy: A Case Report

Abstract

Transformation to squamous cell carcinoma (SCC) after initial treatment of a primary prostate adenocarcinoma is rare and typically results in rapid treatment-refractory disease progression and death. Here, we present a case of a 70-year-old man who was initially treated with prostatectomy and radiotherapy, and later developed bone metastases. After commencing systemic therapy with androgen deprivation therapy (ADT) and apalutamide, his prostate-specific antigen (PSA) declined to undetectable levels, yet short-interval imaging demonstrated oligo-progression at T4, with biopsy specimen demonstrating pure SCC. Molecular profiling of both the primary prostate tumor and T4 demonstrated alterations in TMPRSS2-ERG, TP53, and FOXA1 confirming site of origin, with loss of RNF43 in the squamous metastasis. He was treated with stereotactic body radiation therapy to the SCC metastasis and continued on ADT and apalutamide with stable disease for a year post-radiation. This case highlights the importance of imaging to detect non–PSA-producing metastatic disease, the utility of radiation therapy in oligo-progression, and use of molecular profiling to provide insights into the pathogenesis of histologic transformation.

Post-therapeutic squamous cell transformation of a metastatic prostate adenocarcinoma with comparison of molecular profiles: a case report and review of the literature

“…Squamous cell transformation associated with metastatic prostate cancer is a rare entity that accounts for less than 1% of all prostate malignancies [5]. Although there are a few case reports of squamous cell transformation to date, it has been more commonly seen in primary prostate adenocarcinoma rather than metastatic prostate adenocarcinoma.…”

“…However, there was CCND3 amplification and absence of the TMPRSS2::ETV4 fusion in the later specimen after hormonal therapy, which might suggest that CCND3 amplification and loss of the TMPRSS2::ETV4 fusion may be associated with squamous transformation. In a prior study, Autio and McBride showed loss of RNF43 in the squamous metastasis after initial ADT of a primary prostate adenocarcinoma [5]. Identifying the genetic changes with a molecular panel is very critical in guiding the systemic treatment.…”

“…Up to 17% of patients develop metastatic disease, with the most common site of metastasis being bone (84%), followed by distant lymph nodes, liver, and thorax [4]. In recurrent or metastatic disease, androgen deprivation therapy (ADT), androgen signaling inhibition (ARSI) and che-motherapy comprise the standard medical treatment [5]. The majority of patients with metastatic prostate cancer who receive standard treatment develop "castration resistance", i.e.…”