Vincenza Conteduca1, Clara Oromendia2, Kenneth W Eng3, Rohan Bareja3, Michael Sigouros4, Ana Molina5, Bishoy M Faltas5, Andrea Sboner3, Juan Miguel Mosquera6, Olivier Elemento3, David M Nanus5, Scott T Tagawa5, Karla V Ballman2, Himisha Beltran7. 1. Department of Medicine, Division of Medical Oncology, Weill Cornell Medicine, New York, NY, USA; Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Department of Medical Oncology, Istituto Scientifico Romagnolo per Lo Studio e La Cura Dei Tumori (IRST) IRCCS, Meldola, Italy. 2. Department of Healthcare Policy & Research, Weill Cornell Medicine, New York, NY, USA. 3. Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York, NY, USA; Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA. 4. Department of Medicine, Division of Medical Oncology, Weill Cornell Medicine, New York, NY, USA. 5. Department of Medicine, Division of Medical Oncology, Weill Cornell Medicine, New York, NY, USA; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York, NY, USA. 6. Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York, NY, USA; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA. 7. Department of Medicine, Division of Medical Oncology, Weill Cornell Medicine, New York, NY, USA; Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA. Electronic address: himisha_beltran@dfci.harvard.edu.
Abstract
BACKGROUND: Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer that may arise de novo or in patients previously treated with hormonal therapies for prostate adenocarcinoma as a mechanism of resistance. Despite being important to recognise, the clinical features of NEPC are poorly defined and could help guide when to perform a biopsy to look for NEPC histologic transformation. METHODS: We reviewed baseline, treatment and outcome data of 87 patients with metastatic prostate cancer and tumour biopsy confirming NEPC histology. Forty-seven (54.0%) NEPC cases presented de novo, and 40 (46.0%) were therapy-related (t-NEPC). Thirty-six (41.4%) were classified as pure small-cell carcinoma, and 51 (58.6%) demonstrated mixed features with both small-cell carcinoma and adenocarcinoma present. Genomic data were available for 47 patients. RESULTS: The median age at time of NEPC was 68.1 years, median prostate-specific antigen (PSA) was 1.20 ng/ml (0.14 ng/mL small-cell carcinoma, 1.55 ng/mL mixed carcinoma) and sites of metastases included bone (72.6%), lymph node (47.0%), and viscera (65.5%). Median time from adenocarcinoma to t-NEPC diagnosis was 39.7 months (range, 24.5-93.8) with a median of two lines of prior systemic therapy. Platinum chemotherapy was used to treat 57.5% of patients, with a median progression-free survival of 3.9 months. Small-cell carcinoma was associated with worse overall survival (OS) than mixed histology (8.9 months from NEPC diagnosis versus 26.1 months, P < 0.001). Median OS of de novo NEPC was shorter than that of t-NEPC (16.8 months from prostate cancer diagnosis versus 53.5 months, P = 0.043). An average PSA rise per month of ≤0.7 ng/ml before t-NEPC; elevated lactate dehydrogenase levels, RB1 and TP53 loss and liver metastases were poor prognostic features. CONCLUSIONS: We describe the clinical features of a cohort of patients with NEPC. These characteristics may inform future diagnostic strategies.
BACKGROUND:Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer that may arise de novo or in patients previously treated with hormonal therapies for prostate adenocarcinoma as a mechanism of resistance. Despite being important to recognise, the clinical features of NEPC are poorly defined and could help guide when to perform a biopsy to look for NEPC histologic transformation. METHODS: We reviewed baseline, treatment and outcome data of 87 patients with metastatic prostate cancer and tumour biopsy confirming NEPC histology. Forty-seven (54.0%) NEPC cases presented de novo, and 40 (46.0%) were therapy-related (t-NEPC). Thirty-six (41.4%) were classified as pure small-cell carcinoma, and 51 (58.6%) demonstrated mixed features with both small-cell carcinoma and adenocarcinoma present. Genomic data were available for 47 patients. RESULTS: The median age at time of NEPC was 68.1 years, median prostate-specific antigen (PSA) was 1.20 ng/ml (0.14 ng/mL small-cell carcinoma, 1.55 ng/mL mixed carcinoma) and sites of metastases included bone (72.6%), lymph node (47.0%), and viscera (65.5%). Median time from adenocarcinoma to t-NEPC diagnosis was 39.7 months (range, 24.5-93.8) with a median of two lines of prior systemic therapy. Platinum chemotherapy was used to treat 57.5% of patients, with a median progression-free survival of 3.9 months. Small-cell carcinoma was associated with worse overall survival (OS) than mixed histology (8.9 months from NEPC diagnosis versus 26.1 months, P < 0.001). Median OS of de novo NEPC was shorter than that of t-NEPC (16.8 months from prostate cancer diagnosis versus 53.5 months, P = 0.043). An average PSA rise per month of ≤0.7 ng/ml before t-NEPC; elevated lactate dehydrogenase levels, RB1 and TP53 loss and liver metastases were poor prognostic features. CONCLUSIONS: We describe the clinical features of a cohort of patients with NEPC. These characteristics may inform future diagnostic strategies.
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