Prostate Adenoid Cystic Carcinoma

Introduction

Prostate adenoid cystic carcinoma or prostate basaloid cell carcinoma (PACC/PBCC) is an uncommon type of prostate cancer. Prostate cancer develops in the prostate gland (part of the reproductive system in people assigned male at birth).

In this type, the cancer cells form glandular structures (adenoids) with cysts. This type of carcinoma is also slow-growing and has the potential to spread (metastasis) to nearby tissues and organs.¹

The prostate is a small walnut-shaped gland located below the bladder and in front of the rectum in people assigned male at birth. This gland secretes fluid that mixes with semen, keeping the semen healthy for conception. 

Prostate cancer is a serious disease, and its most common type is called an adenocarcinoma. Carcinoma is the most common type of cancer, which starts in the epithelial tissue of the skin or internal organs. Adenocarcinoma is a subtype of carcinoma where it grows in the glands that line the organs and has the potential to spread to nearby tissue and organs through nerves or the bloodstream. PACC/PBCC is considered to be a rare variant of prostate adenocarcinoma.⁴

Causes and risk factors

Genetic factors and mutations

Genes are made up of DNA (deoxyribonucleic acid), which contains instructions for cell functioning and characteristics that make the person unique. Mostly, DNA gives instructions to the body to make proteins. These proteins start complex cell interactions that keep the person healthy.

A genetic disorder occurs when a mutation (a harmful change to a gene, also known as a pathogenic variant) affects the genes and causes changes in its characteristic nature. Mistakes during cell division may cause mutations, or they may be caused by exposure to DNA-damaging agents in the environment,

When a mutation occurs, it affects the genes' protein-making instructions. There could be missing proteins or proteins that do not function properly. In some conditions, symptoms occur at birth, and in other conditions, it develops over time. These could lead to abnormalities in cells, triggering the development of conditions like cancer. In many cases, carrying the mutation does not always mean that the person will end up with the disease.

Environmental factors(also called mutagens) that could lead to genetic mutation. Some of these include

• Chemical exposure
• Radiation exposure
• Smoking.
• UV exposure from the sun

Age and gender influences

Most commonly, PACC is diagnosed in older people between 50 - 60 years old.¹ 

Occupational and environmental exposures

There are a few factors that contribute to the development of the disease. They are:

• Smoking– Use of cigarettes, cigars and e-cigarettes increases the chance of developing lung, pancreatic, oesophagal and oral cancer
• Diet and exercise– Eating high-fat or high-sugar food can increase the risk of many cancers
• Environment– Harmful toxins from the home or work environment, such as asbestos, pesticides can also cause adenocarcinoma
• Radiation exposure– Ultraviolet (UV) radiation can increase the risk of developing skin cancer. Having previous exposure to radiation treatment can develop the risk factor for cancer.

Symptoms and clinical presentation

Early-stage symptoms

In the early stages of prostate cancer, symptoms are rare.¹ However, symptoms can include  

• Unexplained weight loss
• Chronic tiredness
• Persistent pain
• Fever that occurs mostly at night

Advanced-stage symptoms

As the disease progresses, these symptoms may occur 

• Frequent urination – When you need to urinate too many times, especially at night
• Blood in urine or semen–Also known as haematuria and haematospermia
• Erectile dysfunction (ED)– The inability to get and keep the erection firm enough for sexual intercourse
• Urinary incontinence–Loss of bladder causing uncontrollably leaking urine
• Dysuria–Feeling pain or a burning sensation while urinating
• Faecal incontinence–Also known as anal incontinence, where the bowel movements cannot be controlled. Stool (faeces, waste, poop) leaks out of the rectum during unexpected times.

Differentiating PACC from other prostate cancers

Following is a comparison between PACC and other types of prostate cancers.⁴

Diagnosis

Prostate ACC/BCC diagnosis involves combinations of physical examinations, blood tests, scans and biopsies. These tests can rule out other conditions with similar symptoms and pinpoint the cause, such as prostate cancer.

Medical history and physical examination

The doctor will ask about your medical and family history. They can then perform a digital rectal exam. This involves the doctor checking your prostate gland by feeling the inside of your rectum with a finger while using gloves and lubricant. Any bumps or hard areas on the prostate gland could point towards prostate cancer.^2,4

Other disease conditions that cause similar symptoms to prostate cancer are–

• Benign prostatic hyperplasia (BPH)– It is a condition where the prostate increases in size but is not cancerous. Has similar symptoms of cancer
• Prostatitis is a condition that causes inflammation and swelling in the prostate gland; most often, a bacterial infection is the cause.

Prostate-specific antigen (PSA) test

It is a type of blood test in the prostate gland that makes a protein called a protein-specific antigen (PSA). High levels of PSA may indicate cancer, but they also rise in benign conditions like BPH or prostatitis.

Imaging techniques (MRI, CT, PET)

• Magnetic resonance imaging (MRI)–⁶MRI uses a large magnet and radio waves to capture the images and show them on the screen where the organs and tissue are seen
• Computed tomography scan (CT)–CT scan gives three-dimensional images of the tissues inside the body. It captures cancerous tumours, their location and their impact on the organs and bones.
• Positron emission test (PET) scan–This is an imaging test that produces images of the organs and tissues. In this test, a safe injectable radioactive chemical called a radiotracer is used and a device called a PET scanner is used to produce images.⁵ The scanner detects the diseased cells as they absorb large amounts of the radiotracer.

Biopsy and histopathological analysis

A biopsy is a procedure where the cells, tissues, or fluid are obtained from the affected area or organ for examination by a medical pathologist and are examined under a microscope to see if there are cancer cells.⁶

In the pathology report, we can see the word “differentiation”; this refers to the grade of the cancer. It explains how cancer cells look under a microscope. Well-differentiated adenocarcinoma is considered low-grade. These types of cancer tend to grow and spread slowly. Poorly differentiated adenocarcinoma is considered high-grade cancer because it spreads fast.

Staging and grading

Healthcare providers use the TNM staging system and Gleason score to determine how serious the cancer is and the types of treatment the person needs. They collect information regarding the size and location of the tumour and place the cancer in a specific category or stage, labelled with numbers and letters.⁷

TNM staging system

Tumour-nodes-metastasis (TNM) is the most common cancer staging system. This system gives a stage to cancer based on:

• The size of the primary tumour (T)
• The number of nearby lymph nodes the cancer has spread to (N)
• The spread from the primary tumour to other areas of the body or metastasis (M)

There are four stages of cancer, according to the TNM information, they are:

• Stage Ⅰ– This stage includes small tumours which have not spread to lymph nodes or other areas of the body
• Stage Ⅱ– This stage includes larger tumours that have not spread to nearby lymph nodes or other areas of the body
• Stage Ⅲ– This stage includes large tumours that have spread to nearby lymph nodes but not to other areas of the body
• Stage Ⅳ– This stage includes metastatic cancer, which means cancer has spread from the primary tumour to other areas of the body

Gleason score and grading system

Samples taken from a biopsy can be used to predict how quickly the tumour will grow. The biopsy sample will look at how many of the cells are cancerous and how faulty they are. These two areas are used to calculate a Gleason score. Depending on the score, a grade is given, which predicts how likely the tumour is to grow and how fast it might do so.⁸ Gleason scores help to predict how quickly prostate cancer grows. Tumours with higher Gleason scores are likely to grow quickly. There are 3 categories, they are:

• Gleason 6 or lower– The cells are healthy, which is well-differentiated
• Gleason 7– These cells are similar to healthy cells, which are called moderately differentiated
• Gleason 8,9 or 10– These are poorly differentiated or undifferentiated cells

Treatment options

Treatment of PACC depends on whether the cancer is limited to the same area that it started (localised), how large the tumour is and if it has spread to other areas of the body. 

Localised PACC

Surgery (radical prostatectomy)

During radical prostatectomy surgery, the diseased prostate gland is removed, and it can often eliminate prostate cancer if it has not spread.¹ 

• Open radical prostatectomy– The surgeon makes a single cut into your abdomen, from the belly button to the pubic bone and removes the prostate gland
• Robotic radical prostatectomy– This is a minimally invasive surgery where robotic equipment is used to remove the entire prostate. The laparoscopic technique allows the surgeon to operate through small ports rather than large incisions, resulting in shorter recovery time, and fewer complications

Radiation therapy

Radiation therapy is a commonly used treatment for cancer that uses radiation to kill cancer cells. Radiotherapy for PACC includes:

• Brachytherapy– It is an internal radiation therapy where radioactive seeds are placed inside the prostate, which kills the cancer cells while preserving surrounding healthy tissue.
• External beam radiation therapy– In this method, a machine delivers strong X-ray to the tumour

Cryotherapy

Cryotherapy is a treatment where they apply extreme cold to freeze and destroy cancerous tissue. To create this severe cold liquid, nitrogen or argon gas is used.

Locally advanced or metastatic PACC

Androgen deprivation therapy (ADT)

It is also known as hormonal therapy, where hormone-sensitive cancers are managed, including prostate cancer. The main aim of ADT is to lower the levels of androgen as it stimulates the growth of prostate cancer cells.

Chemotherapy

Chemotherapy is the most common cancer treatment and involves powerful drugs that are used to destroy the cancer cells. Chemotherapy is received in pill form or intravenously (through a needle into the vein).⁹

Immunotherapy

Immunotherapy cancer treatment uses the body's immune system to find and destroy cancer cells.

Targeted therapy

Targeted therapy is a kind of cancer treatment that focuses on genetic changes or mutations that turn healthy cells into cancer cells.³

Palliative care and symptom management

Unfortunately, not all cases of prostate cancer can be cured. For people who cannot be cured, treatment focuses on helping them live the rest of their lives at the best quality of life. This includes pain management, helping with symptoms (urinary incontinence, sleeplessness), nutritional support, and providing emotional and psychological support.

Prognosis and survival rates

Factors affecting prognosis

The prognosis depends on the type, location, and size of the tumour. Cancer that is difficult to diagnose in early stages is more likely to be fatal than cancers that are detectable early on. 

Survival rates for different stages of PACC

The survival rate depends on the type of carcinoma, its stage when diagnosed and its location. However, more than 99% are alive after 5 years of treatment.

Follow-up and surveillance

Regular monitoring and check-ups

Regular monitoring helps the doctor evaluate how well the treatment is working. This will include blood tests and scans to check the progress of treatment while also checking to see if there are any changes to the tumour or if it has spread. It is advised to seek medical attention immediately when new symptoms occur or if existing symptoms worsen.

PSA testing and imaging studies

PSA testing helps to monitor any significant changes over time, but this is not reliable as the PSA level increases in both normal and cancerous prostate cells. Imaging studies such as transrectal ultrasound, magnetic resonance imaging (MRI), and computed tomography (CT) may be performed periodically to evaluate the status of the prostate adenoid cystic carcinoma, monitor the presence of the metastasis or monitor any change in tumour or surrounding tissues.

Summary

Prostate adenoid cystic carcinoma (PACC) is a rare form of prostate cancer. It involves changes to genes, resulting in prostate cells reproducing uncontrollably and not being able to repair themselves when they are faulty. These changes can be inherited from our parents or develop naturally when our cells reproduce. However, they can also be caused by certain chemicals and radiation.

PACC is diagnosed by a combination of physical exams, scans, blood tests and biopsies. Treatment depends on the stage and location of the tumour but commonly includes surgery, chemotherapy, radiotherapy and targeted treatment.