Types of Prostate Cancer: A Tissue-Level Overview

While cancer may seem like an all-encompassing disease, it actually comprises a substantial number of subtypes which can influence progression, treatment options and expected outcomes. These can be identified by biopsy and histopathological analysis of their tissue morphology. Here, we present some commonly recognized types of prostate cancer.

First and foremost, the majority of prostate cancer cases arise as adenocarcinomas. These develop in gland cells of the prostate, as well as its linked ducts. Diagnosis is done by identifying structural irregularities that differentiate actual cancerous tissue from pre-cancerous cases of high-grade prostatic intraepithelial neoplasia (PIN). These include irregular cell sizes, the loss of the basal cell layer, and overly large nuclei.

The most common prostate cancer is acinar adenocarcinoma, a subtype known for unique patterns in its morphology. According to the 2022 classification by the World Health Organization (WHO), this can include variants that may appear misleadingly benign and difficult to diagnose (e.g. atrophic, pseudohyperplastic, microcystic or foamy), as well as others that may signal a worse prognosis (e.g. sarcomatoid, pleomorphic giant cell, mucinous or signet ring cell).

While uncommon, ductal adenocarcinoma remains the second most frequently encountered subtype of prostate cancer. It is often found in the central ducts of the prostate, but may also be found as a protruding lesion from the portion of the urethra that passes through the prostate. Most lesions typically develop in later stages of the cancer, as the cancer grows to take over previously healthy ducts of the prostate. In terms of speed, it's more aggressive than acinar adenocarcinoma and spreads faster.

More common symptoms include issues with obstructed urination and blood in urine. These symptoms should be noted as they are associated with worsened prognosis and higher chances of invasion and metastasis into nearby lymph nodes and seminal vesicles.

An aggressive prostate cancer subtype, neuroendocrine prostate cancer usually develops late in disease progression. Commonly seen morphology includes oat cell and intermediate cell patterns. While tough to counter, the aggressiveness seen in this subtype can be explained by understanding how it develops.

Neuroendocrine prostate cancer generally develops from castration resistant prostate cancer (CRPC), but can develop on its own as well. When CRPC grows resistant to androgen deprivation therapy, it finds other methods to reactivate cellular signaling through the androgen receptors (ARs), thereby evading the initial treatments delivered.

For as long as CRPC still relies on ARs to sustain itself, different methods can be used to attempt to block the AR pathway. Unfortunately, about 15–20% of CRPC tumors will eventually adapt to overcome this dependence, managing to persist without relying on working ARs. Neuroendocrine prostate cancer is one type of prostate cancer that does this.

In neuroendocrine prostate cancer, tumor cells have developed alternative strategies for survival, rather than simply relying on the AR pathway. For example, they could learn to evade programmed cell death or hack their cell cycle, speeding up how fast they proliferate. Subsequently, this prostate cancer type is able to spread much more aggressively.

Ultimately, understanding your prostate cancer subtype and its complexities will help you to understand the treatment management decisions your doctor recommends, as well as the significance of new clinical trials and results for you. Adding to that, however, it is good to remember that these classifications are actively being discussed. As new data arrives, updates may be likely, and researchers may reach a new consensus on how to best treat your cancer subtype.

In the future, cancer genomics may also play a much bigger role in prostate cancer treatment, by identifying the unique genetic and molecular makeup of each tumor, in order to select the best treatment possible for you. To ensure that you are making the best decisions for your health, it is advisable to stay informed and up-to-date on the latest information and developments in prostate cancer.