Optimizing the diagnosis and management of ductal prostate cancer

• Published in: Nature reviews. Urology Vol. 18; no. 6; pp. 337 - 358
• Main Authors: Ranasinghe, Weranja, Shapiro, Daniel D., Zhang, Miao, Bathala, Tharakeswara, Navone, Nora, Thompson, Timothy C., Broom, Bradley, Aparicio, Ana, Tu, Shi-Ming, Tang, Chad, Davis, John W., Pisters, Louis, Chapin, Brian F.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-06-2021; Nature Publishing Group
• Subjects: 631/337; 631/67/1059; 631/67/589/466; Androgens; Biology; Cancer therapies; Carcinoma, Ductal - diagnosis; Carcinoma, Ductal - therapy; Care and treatment; Diagnosis; Evaluation; Histopathology; Humans; Male; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Metastasis; Pathology; Practice guidelines (Medicine); Prostate cancer; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - therapy; Review Article; Urology; United States
• ISSN: 1759-4812; 1759-4820
• DOI: 10.1038/s41585-021-00447-3

Ductal adenocarcinoma (DAC) is the most common variant histological subtype of prostate carcinoma and has an aggressive clinical course. DAC is usually characterized and treated as high-risk prostatic acinar adenocarcinoma (PAC). However, DAC has a different biology to that of acinar disease, which often poses a challenge for both diagnosis and management. DAC can be difficult to identify using conventional diagnostic modalities such as serum PSA levels and multiparametric MRI, and the optimal management for localized DAC is unknown owing to the rarity of the disease. Following definitive therapy for localized disease with radical prostatectomy or radiotherapy, the majority of DACs recur with visceral metastases at low PSA levels. Various systemic therapies that have been shown to be effective in high-risk PAC have limited use in treating DAC. Although current understanding of the biology of DAC is limited, genomic analyses have provided insights into the pathology behind its aggressive behaviour and potential future therapeutic targets.
Ductal adenocarcinoma of the prostate is the most common variant histological subtype of prostate cancer. The diagnosis can be challenging and evidence for treatment is predominantly based on retrospective data. This Review discusses the histopathology, characteristics, treatment options and future molecular targets for treatment of this disease.
Key points
Ductal adenocarcinoma (DAC) is the most common variant histological subtype of prostate carcinoma, which has a unique and aggressive biology.
In contrast to prostatic acinar adenocarcinoma (PAC), the majority of DACs present with lower urinary tract symptoms, have a low serum PSA and are often clinically under-staged.
DAC tends to present with advanced disease and has poor outcomes with surgery or radiotherapy compared with high-risk PAC. Multimodal therapies are often needed upfront when treating localized DAC.
The genomic makeup of DAC resembles castration-resistant PAC and warrants aggressive therapy, including the use of upfront use of novel systemic or combination therapies in neoadjuvant, adjuvant and metastatic settings.
Aggressive surveillance post-radical therapy for localized disease with imaging, including CT of the chest, is warranted, as patients with DAC develop bony and visceral metastases at low PSA levels.