Reviewed by: HU Medical Review Board | Last reviewed: October 2017 | Last updated: February 2022
Although PSA (prostate-specific antigen) tests, digital rectal exams (DRE’s), and core needle biopsies are tools used to obtain a prostate cancer diagnosis, there are still several conditions that can be present that are considered prostate pre-cancers. While research is ongoing in relation to how strong of an association these conditions have with developing prostate cancer, it is believed that several of these may predict future prostate cancer more than others.
Oftentimes, these pre-cancerous conditions are found by chance, during evaluation of tissue samples from a biopsy, or after undergoing treatment for another condition, such as transurethral resection of the prostate (TURP) for BPH (benign prostatic hyperplasia), a condition that is not pre-cancerous.1
Most of these conditions aren’t treated, as few treatment options, if any, have been shown to decrease the risk of developing prostate cancer enough to justify their cost and risk.
These findings are typically found by a pathologist analyzing prostate tissue samples, known as cores, with a microscope during a biopsy. Although the same diagnosis may not be found in every core, the following findings are considered to be associated with an increased risk of developing, or already having, prostate cancer.2
What does Prostatic Intraepithelial Neoplasia (PIN) mean?
PIN is discovered during an estimated 9-14 percent of biopsies and can affect more than one area of the prostate. Although PIN cells look abnormal under a microscope, they are not considered cancerous and are considered lesions that cannot metastasize.
PIN is very common. It has been estimated that nearly half of all men will have some evidence of PIN in their prostate by the time they are 50 years old, and that PIN can begin to develop as early as 20 years old.
PIN is classified into two categories, high grade PIN and low grade PIN, with only high grade PIN considered a precursor to prostate cancer. Low grade PIN is classified as having cell patterns that are almost normal, while high grade PIN is classified as having cell patterns that are more abnormal. Neither classification of PIN raises PSA levels, nor is detected during a DRE. This is why PIN is found during the biopsy process or during a surgical procedure like TURP.
PIN can be found in acini cells, clumps of cells that line the prostate gland and make the fluid that will eventually become semen, or in the ducts of the prostate, similar to the most common type of prostate cancer, adenocarcinoma. However, the basal cell layer is still present in PIN, meaning that the cells have not invaded the basement membrane of the prostate, a key feature when diagnosing prostate cancer. PIN can sometimes be found in areas adjacent to developed prostate cancer, which is why determining if further follow-up is needed is often unclear.
Low grade versus high grade PIN
Low grade PIN is not considered a prostate pre-cancer, and is often not recorded on a biopsy report at all. It has even been estimated that the chance of finding prostate cancer on a repeat biopsy after discovering low grade PIN may actually be less than finding prostate cancer on a repeat biopsy on someone without PIN. For this reason, no action or treatment is taken after finding low grade PIN.
High grade PIN, on the other hand, is typically considered a pre-cancer and is indicative of roughly a 20-percent chance of having cancer in another area of the prostate or of developing prostate cancer within the next 10 years.
Although the chance of developing or having prostate cancer after finding high grade PIN is higher, it doesn’t mean that this is guaranteed. For this reason, immediate repeat biopsies or treatment options carry risks or costs that exceed their benefit, and no action is typically taken. If a biopsy returns that has high grade PIN, it is best to talk with your doctor about the most appropriate next steps for your specific situation.1-6
Proliferative Inflammatory Atrophy (PIA)
Atrophy means to shrink or get smaller, which is what prostate cells with PIA look like under a microscope. Prostate cells appear smaller than normal, and although this condition is not cancerous, it is thought it may lead to high grade PIN or prostate cancer in the future. PIA presents with inflammation and degradation in similar areas to those in which PIN is found, and also, where most prostate cancers develop.
It is unclear how PIA starts or what it could turn into, however, it’s been hypothesized that it develops after toxin exposure, infection, or another inflammation-causing event. Chronic inflammation in other parts of the body are often thought to contribute to cancer development, which is why PIA as a prostate cancer pre-cancer is not out of the range of possibilities.1,4,6
Atypical Small Acinar Proliferation (ASAP) on a biopsy
ASAP is a lesion characterized by the abnormal growth of prostate gland cells. ASAP lesions mimic cancer, and indicate that cancer may be present, however, there are too few, or their qualities are too undefined to make a definitive prostate cancer diagnosis. Because of this, it is possible that those with ASAP may already have prostate cancer in another part of the gland, or are in the process of developing the condition. ASAP is only identified in roughly 2 percent of biopsies, however, subsequent biopsies indicate prostate cancer in nearly 60 percent of individuals with initial ASAP.
ASAP can also be found in combination with high grade PIN, in which case, it has been theorized that the risk of developing prostate cancer is further increased. However, ASAP alone is more commonly considered a prostate pre-cancer than PIN on its own. Once ASAP is found, an immediate repeat biopsy is not always necessary. Many individuals and their providers may opt for a follow-up biopsy six months later in order to identify more definitive results.1,7,8
Other prostate concerns
As mentioned before, many of the potential pre-cancers listed are found incidentally during a biopsy or TURP surgery for BPH. Although treatment for BPH may lead to an increased chance of finding one of these asymptomatic pre-cancers, BPH itself is not a pre-cancerous condition. BPH is characterized by the enlarging of the prostate as a result of aging and not a malignant process.
Eventually, the prostate can become large enough that it presses on the urethra (the tube that carries urine out of the body) causing difficulties in urination. When this happens, TURP may be necessary to alleviate this issue, and prostate pre-cancers may be identified during the treatment process.
Additionally, prostatitis, or common inflammation of the prostate gland, can be caused by infection or another inflammation-causing event that can be treated with antibiotics, other medications, and additional management strategies. Although prostatitis may require treatment, it is not an indicator of future prostate cancer, and is often short term.
Finally, another potential finding from a prostate core tissue biopsy is atypical adenomatous hyperplasia, or adenosis. Although this sounds like a malignancy, it is a benign condition that is also not considered a prostate pre-cancer.2