(UroToday.com) The 2023 EAU annual meeting included a joint session of the EAU and the Advanced Prostate Cancer Consensus, featuring a presentation by Dr. Eva Comperat discussing how among patients with high-risk localized disease, M0 on conventional imaging but one bone lesion on PSMA PET/CT, subtypes of prostate cancer can change our management. For patients with rare subtypes, Dr. Comperat notes that Gleason score is not sufficient for risk stratification. For acinar prostate cancer, different histological patterns include (i) atrophic acinar adenocarcinoma, (ii) pseudohyperplastic acinar adenocarcinoma, (iii) microcystic acinar adenocarcinoma, (iv) foamy gland acinar adenocarcinoma, and (v) mucinous (colloid) acinar adenocarcinoma. The specific subtypes (morphologically distinct and have prognostic significance) for acinar prostate cancer include:
- Pin-like: mimics high-grade PIN, has a favorable prognosis, and treatment is like other Gleason 3+3 prostate cancers
- Signet-ring cell like: >25% of tumor cells is considered diagnostic, surgery is the optimal treatment, it is unclear with regards to the strategy of adjuvant therapy, and overall survival is typically <32 months
- Sarcomatoid: Mostly occurs after radiotherapy, is extremely rare, and treatment is unclear
- Pleomorphic: Many cases arise after prior ADT or radiotherapy, it has a diverse molecular alteration profile, and is perhaps best treated with chemohormonal therapy
Ductal adenocarcinoma is considered pattern 4, is aggressive disease, makes up 0.17% of prostate cancers, and when associated with comedonecrosis is considered pattern 5 disease. Historically, there has also been a problem of under-staging at the time of biopsy diagnosis. These are typically large tumors, with increased risk of advanced disease: mixed and pure ductal carcinoma have worse metastasis free survival after radical prostatectomy than acinar prostate cancer, and any proportion of ductal carcinoma in a biopsy carries an increased risk of biochemical recurrence. Furthermore, compared to high risk conventional adenocarcinoma, ductal carcinoma is less responsive to ADT, and surgery or radiotherapy should be used for treatment of localized disease. In patients that are metastatic, they should be treated with hormonal or chemotherapy. Ductal carcinoma can metastasize to unusual sites, including the penis and peritoneum:
Almost all prostate cancer displays some degree of (focal) neuroendocrine differentiation if associated with a high Gleason score. Treatment related neuroendocrine prostate cancer has the following characteristics:
- Transdifferentiation of a CRPC after potent ADT
- Develops less than 24 months after ADT
- Survival is typically only 7 months
- The tumor does not respond to AR-targeting
- Has overexpression of epigenetic regulators
N-MYC and AURKA overexpression is a predictive biomarker for transformation to treatment related neuroendocrine prostate cancer, and AURKA amplification is found in 65% of localized cases and 86% of metastatic lesions. Concurrent amplification of N-MYC is found in 70% of primary tumors and 83% of metastases.
Regular neuroendocrine prostate cancer if pure has no Gleason grading and ~50% of tumors that are identified with a neuroendocrine prostate cancer component represent mixed NETumors. Neuroendocrine prostate cancer is probably a separate clinical entity and mixed tumors typically are associated with a poorly differentiated ADK component:
Treatment of neuroendocrine prostate cancer is difficult and may be an excellent target for 177-Lutetium PSMA or a theranostic small-molecule prodrug conjugate (T-SMPDC).
Adenoid cystic cancer/basal cell carcinoma is genetically and morphologically a type of adenoid cystic carcinoma, but has recently been renamed adenoid cystic (basal cell) carcinoma of the prostate:
These are associated with a low PSA, AMACR/AR negative, ERG negative, BLC2++, increased expression of Ki67, as well as overexpression of HER-2/neu. Extraprostatic extension is common after radical prostatectomy in 44-71% of cases, 14-29% become metastatic, and 50% lead to death from prostate cancer. Treatment has been pemigatinib.
Dr. Comperat concluded her presentation with the following take-home messages:
- Recognition of unusual patterns and rare subtypes is important for risk stratification
- These subtypes can sometimes be difficult to recognize (particularly ductal carcinoma on biopsies)
- Subtypes add to prognosis and treatment options, with some having distinctive clinical behavior
- All subtypes, except PIN-like are more aggressive than standard prostate adenocarcinoma
Presented by: Eva Comperat, MD, PhD, Medical University of Vienna, Vienna, Austria
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 European Association of Urology (EAU) Annual Meeting, Milan, IT, Fri, Mar 10 – Mon, Mar 13, 2023.
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