Remarkable Response to Etoposide and Cisplatin in Aggressive-Variant Prostate Cancer With Low Prostate-Specific Antigen Levels: A Case Report

Prostate-specific antigen (PSA) is a cornerstone of screening for prostate cancer (PC); however, serum PSA levels may remain deceptively low in certain high-grade, aggressive subtypes. Aggressive-variant prostate cancer (AVPC) is a clinical entity characterized by rapid progression, bulky lymphadenopathy, and visceral metastases despite low or non-correlative PSA levels, often requiring treatment approaches beyond conventional therapies. Here, we report the case of a 69-year-old Japanese man with multiple comorbidities, including diabetes, hyperlipidemia, hypertension, angina pectoris, and lower limb occlusive arteriosclerosis, who presented to our center with lower back pain and gait disturbance. Diagnostic imaging demonstrated extensive pelvic bone metastases, seminal vesicle invasion, and pelvic and para-aortic lymphadenopathy. Laboratory evaluation showed a normal PSA level of 2.95 ng/mL and an elevated alkaline phosphatase (ALP) of 669 U/L. A prostate biopsy revealed acinar adenocarcinoma with a Gleason score of 8 (4+4) and intraductal features. Immunohistochemical tests showed positive results for NKX3.1 and androgen receptor but negative results for PSA, synaptophysin, and chromogranin A. Given these findings, the patient was diagnosed with AVPC (cT3bN1M1b) and underwent androgen deprivation therapy combined with etoposide and cisplatin (EP) chemotherapy, achieving a partial response with marked improvements in his symptoms and lymph node lesions. Subsequent radium-223 therapy further reduced bone metastases and normalized ALP levels, leading to substantial functional recovery. This case underscores the necessity of maintaining a high index of suspicion for AVPC when clinical findings contradict low PSA values. Furthermore, the favorable response to EP highlights the potential role of platinum-based chemotherapy in managing low-PSA, high-grade PC. Additional cases are needed to refine the clinical characterization of AVPC and establish evidence-based treatment guidelines.