Ductal prostate cancer is a rare type of prostate cancer. Men diagnosed with ductal prostate cancer are more likely to see their cancer spread and more likely to die from it. This week’s research blog investigates what is known about ductal prostate cancer and how it’s best treated.
Prostate cancer is the most commonly diagnosed cancer in Australian men. Like most common cancers, decades of research and clinical trials means that we know a lot about prostate cancer and there are many treatments available. As so many people are affected by prostate cancer worldwide, there are many foundations, support groups, booklets, online communities, webcasts and other sources of support and information available. Men with prostate cancer can also be treated by health professionals who have treated hundreds or thousands of similar cases before. Clinical trials give them a lot of information by which to recommend most the appropriate treatments.
It’s a completely different story for people who have rare cancers.
Rare cancers in Australia
Approximately 52,000 people are diagnosed with a rare cancer each year in Australia and 25,000 people die from them. Rare cancers include over 200 different types of cancer. Over the last 20 years, the survival rates for rare cancers have only slightly improved. The survival rate for prostate cancer, on the other hand, has dramatically increased over the past 25 years. Research into rare cancers is also sparse compared to common cancers.
People who are diagnosed with a rare type of cancer are faced with many issues. They often find that few treatment options are available. They see clinicians who have very little experience in treating the cancer that they have. Very limited information is available to help them understand their own disease. Many people with rare cancers turn to treatments that are not government-funded or only available overseas. This creates a huge financial burden for them. People with rare cancers must face multiple difficult issues at the same time as they are fighting cancer.
Rare prostate cancers
Some men diagnosed with prostate cancer are surprised to be told that they have a rare type of prostate cancer. This puts them in a similar situation as those with rare cancers. There is less information available to help them and their doctors only rarely see men with the same type of prostate cancer. But treatments for the common type of prostate cancer are usually used by those with a rare type.
The most common type of prostate cancer is called acinar adenocarcinoma. Rare types of prostate cancer differ to acinar adenocarcinoma because they are derived from different types of prostate cells, or different things gone wrong with the prostate cells that lead to them becoming cancerous. Among the numerous rare prostate cancers are:
Neuroendocrine prostate cancer
Neuroendocrine cancer cells develop from normal (non-cancerous) neuroendocrine cells that are found in the prostate gland. The exact role of normal neuroendocrine cells in the prostate is unknown. They have features similar to nerve cells and cells that secrete hormones.
Ductal prostate cancer (ductal adenocarcinoma)
Although rare, this is the second most common type of prostate cancer. It develops from prostate gland cells and is usually located near the prostate ducts. Mucinous Prostate Cancer also derives from prostate gland cells. Ductal prostate cancer is not the same as intraductal carcinoma of the prostate – this is a subtype of the typical adenocarcinoma that is associated with rapid disease progression.
Signet ring cell prostate cancer
This very rare type of prostate cancer usually has high PSA levels, so it can be detected using a PSA test. It’s thought to be derived from prostate gland cells.
Basal cell prostate cancer
These rare tumours usually don’t have high PSA levels. Very little is known about them.
Transitional cell prostate cancer
Transitional cell prostate cancer usually starts in the bladder then moves to the prostate. But some start in the prostate, making them a rare form of prostate cancer.
Rhabdomyosarcoma
Rhabdomyosarcomas in the prostate are more common in children and younger men. They are aggressive cancers that often spread to other regions. There are a number of other types of sarcomas that also start growing in the prostate.
Ductal prostate cancer
Also referred to as ductal adenocarcinoma of the prostate
Ductal prostate cancer is a rare form of prostate cancer. It can occur in two different ways: on its own (pure), and mixed with typical prostate cancer. Some men are diagnosed with pure ductal prostate cancer, where these are the majority of cancerous cells detected. This occurs in approximately 1% of men with prostate cancer. Ductal prostate cancer cells can also be seen mixed with the typical prostate cancer (acinar adenocarcinoma) cells in up to 6% of men with prostate cancer. Herein “ductal prostate cancer” refers to the pure form, which is usually classified as pure when 75% or more of the cancerous cells are ductal prostate cancer cells.
Ductal prostate cancer is referred to as such because the cancer cells affect the prostate ducts. The prostate produces fluid that mixes with sperm to make up the semen. This fluid, called seminal plasma, leaves the prostate through ducts. These tiny vessels join together to form a larger duct from which the seminal plasma flows out of the prostate during ejaculation. The ducts are therefore close to the urethra, the tube through which both semen and urine flows. Ductal prostate cancer often causes disruption to urine flow. It is usually detected during transurethral resection (TURP) procedures to treat enlarged prostates.
Ductal prostate cancer usually affects men between 60 and 80 years old. PSA levels are usually lower than expected and some men have no rise in PSA at the time they are diagnosed. For ductal prostate cancer, PSA levels are not a particularly good indication of the tumour stage, risk of return after treatment and presence of metastasis (tumours spread to far regions). A digital rectal exam (DRE) is usually ineffective at detecting ductal prostate cancer, as the prostate feels relatively normal despite the cancer. Ductal prostate cancer spreads in a similar manner to the typical adenocarcinoma, but it is more likely to spread to the testicles and penis.
Ductal prostate cancer is usually more aggressive than the typical adenocarcinomas. Most patients have high-risk or advanced cancer at the time of diagnosis. Unfortunately, diagnosis is usually delayed due to the low PSA levels and normal DREs. A study from 2009 showed that over 80% of men diagnosed with ductal prostate cancer have a Gleason score of 8 or over. Men who have pure ductal prostate cancer have an increased risk of cancer return after initial treatment, but this was not so for men with a mix of ductal and typical prostate cancer.
Treatments for ductal prostate cancer are similar to those for typical prostate cancer. They include surgery, radiotherapy, hormone therapy (Androgen Deprivation Therapy: ADT) and chemotherapy. Unfortunately each of these treatments is less effective for ductal prostate cancer than for typical prostate cancer. Surgery often cannot remove all the cancer. Fortunately, ADT is an effective treatment that usually slows the growth the ductal prostate cancer.
Research into ductal prostate cancer
Since ductal prostate cancer is rare, research into this disease is also rare. In 2017, there were 8,794 scientific publications that mention prostate cancer, but only 42 that mention ductal prostate cancer. Many of the early published studies focus on how to recognise ductal prostate cancer in biopsy samples. A search of the US Clinical Trials database found no trials specifically recruiting men with ductal prostate cancer. Only three trials mentioned ductal prostate cancer in their summaries. Each of these trials recruited men with the typical prostate adenocarcinoma, but mentioned that men with ductal prostate cancer were also able to join the trial.
A study published in 2010 showed that ductal prostate cancer had a lower survival rate and lower PSA levels than typical prostate cancers. The researcher from the US used a national cancer registry to find patient records from 1996 to 2006. They identified and compared over 440,000 cases of typical prostate adenocarcinoma to 371 cases of ductal prostate cancer. These records showed that PSA levels for men with ductal prostate cancer were an average 30% lower than for men with typical prostate cancer. Men with ductal prostate cancer were 2.4 times more likely to die from this disease than men with typical prostate cancer. This appears to be due to ductal prostate cancers being detected at a late, advanced stage. Survival rates were very similar between the two types of prostate cancer once the disease had reached the metastatic stage. The researchers concluded that since ductal prostate cancers were more likely to be diagnosed at an advanced stage with low PSA, detecting this disease at the early stages remains a significant challenge.
Some studies have investigated the differences between ductal prostate cancer and the typical prostate adenocarcinoma. Genetic studies have asked which genes are turned on in the two different types of cancer cells. Results showed that the two cancer types are surprisingly similar. Only 25 genes were shown to be used differently by the cancers.
A common feature of many typical prostate cancers is called the TMPRSS2-ERG fusion gene. This is a mix of two genes that have become stuck together, which causes problems in the cells. The TMPRSS2-ERG fusion gene is present in over half of typical prostate adenocarcinomas but was rarely present in ductal prostate cancer cells. A similar study found that alterations in the genes called CTNNB1 and PTEN were common in ductal prostate cancer. While these studies have not yet helped to find a good treatment for this disease, they do help us to understand the basic characteristics of ductal prostate cancer.
A 2016 study of 10 men with ductal prostate cancer showed that DNA repair genes were commonly affected. Although this study is too small for definite conclusions, this work indicates that some immunotherapies might be useful for these patients. However, there are no published studies testing immunotherapies for men with ductal prostate cancer.
Although no large clinical trials have tested treatments specifically for ductal prostate cancer, there have been numerous case reports on this disease. Case reports describe in detail the patient journey of one or a few people. One very useful case report from Japan has described chemotherapy treatment for two patients. Chemotherapy with docetaxel is often reported as less effective for ductal prostate cancer than typical prostate cancer. The Japanese case report described treatment of the two patients with gemcitabine and cisplatin after docetaxel chemotherapy. Each patient had metastatic ductal prostate cancer, where tumours had spread to far sites. One of the patients experienced shrinking of ductal prostate tumours in his lung after this treatment. The other patient had some success in slowing the growth of lung and bone tumours. The authors concluded that treatment with gemcitabine and cisplatin is a potential option for men with metastatic ductal prostate cancer. But more research is necessary to determine the exact benefits of these drugs as well as the expected side effects.
