PSA Levels in Metastatic Prostate Cancer

The main purpose of this article is to enlighten you on the PSA levels in metastatic prostate cancer.

Prostate cancer with local metastasis means that the cancer in ones body has spread to other organs within the pelvis, which usually means the nearby lymph nodes. And it’s usually includes any organ or structure in the pelvis. If the  prostate cancer spreads to other parts of the body, the doctor may tell that it is “metastatic” or that the cancer has “metastasized.”

Most often, prostate cancer spreads to the bones or lymph nodes and it’s also common for it to spread to the liver or lungs and very rarer for the cancer to move to other organs, such as the brain. It is still called prostate cancer even when it spreads. For example, metastatic prostate cancer in a bone in the hip is not bone cancer. It has the same prostate cancer cells the original tumor had.

Metastatic prostate cancer is an advanced form of cancer although there is  no cure but one can treat it and control it. Most men with advanced prostate cancer live a normal life for many years. Some cancers are called “locally advanced.” That means the cancer has spread from the prostate to nearby tissue. It’s not the same as metastatic cancer since it hasn’t spread to other parts of your body. Many locally advanced prostate cancers can be cured.

Chances of Developing Metastatic Prostate Cancer

About 50% of men diagnosed with local prostate cancer have a very high chances of developing metastatic cancer during their lifetime so finding cancer during it’s early stage and treating it can lower that rate. A small percentage of men are not diagnosed with prostate cancer until it become metastatic. Note: Doctors can find out if it’s metastatic cancer when they take a small sample of the tissue and study the cells.

How Doctors Diagnosed Metastatic Prostate Cancer

When a patient is diagnosed with prostate cancer, the doctor will order tests such as;

  • X-rays
  • CT scans
  • MRI scans
  • PET scans

These tests focuses on the skeleton, the belly and pelvic areas and in the above ways doctors can check for signs that the cancer has spread or if the cancer is metastatic. If one’s have symptoms such as bone pain and broken bones for no reason, the doctor may order a bone scan and it may show if you have signs of cancer spread in the bones. The doctor will also ask for blood tests, including a check of PSA levels, to look for other signs that the cancer is spreading.

What is PSA

PSA is a protein that is made by the prostate gland. A rise in the PSA levels in metastatic prostate cancer is one of the first signs that cancer may be growing but PSA levels can also be high without there being cancer like if one have an enlarged prostate or prostate infection, trauma to the perineum, sometimes sexual activity can also cause PSA level to be high. Distant metastasis means that prostate cancer has spread beyond the pelvis. The bones, brain, liver, and lungs are common sites of cancer metastasis.

In many cases, prostate cancer grows very slowly, some men do not even realize that they have the disease. Sometimes, the disease metastasizes to other organs away from the prostate. When prostate cancer metastasizes, it can become much harder for a doctor to treat.

Symptoms of Metastatic Prostate Cancer

Usually, prostate cancer is has no symptom but however, when symptoms do occur, they may include;

  • Frequent urination
  • Difficulty in controlling urination
  • Weak or interrupted urine flow
  • Pain or burning when urinating
  • Erectile dysfunction
  • Painful ejaculation
  • Producing less semen when ejaculating
  • Blood in the urine or semen.

Many other conditions, including prostatitis and benign prostatic hypertrophy, can cause similar symptoms. However, anyone experiencing these symptoms should consult their doctor as soon as possible to rule out prostate cancer.

Complications

Once a doctor makes a diagnosis of prostate cancer, complications from metastasis will depend on where the cancer spreads to, and how quickly it is growing e.g a person with prostate cancer that has spread to nearby lymph nodes may not experience any change in symptoms. When prostate cancer metastasizes to the following areas, it can cause a range of complications;

  • Bone: This can cause fractures and pain.
  • Brain: This can lead to dizziness, headaches, and seizures.
  • Liver: This can lead to jaundice and swelling in the abdomen.
  • Lungs: This can lead to shortness of breath.

PSA Levels in Metastatic Prostate Cancer

Advanced T stage, high Gleason grades and high serum levels of prostate-specific antigen (PSA) are related with bone metastases in men living with prostate cancer. Based on results from some small, single centre studies that was published in the beginning of the 1990s, PSA levels in metastatic prostate cancer above 100 ng/mL has been used as a proxy for metastatic prostate cancer.

But however, the identification and quantification of metastases is increasingly very important since radical treatment in men with very high-risk, non-metastatic prostate cancer have been suggested to be beneficial in observational studies and quantification of tumor extent is used as a basis for selection of novel treatments in addition to androgen deprivation therapy in men with advanced prostate cancer.

Recently, two observational studies has reported that among men living with PSA levels in metastatic prostate cancer 100 ng/mL or higher who had undergone bone imaging, only but 45-75% had metastatic prostate cancer. These studies were hampered by few men with PSA levels in metastatic prostate cancer >100 ng/mL (n = 241) or the possibility of selection bias since only men who had undergone imaging were included in a previous PC base study (7 521 out of 15 635 men with PSA levels in metastatic prostate cancer above 100 ng/mL).

To avoid this situation, the application of imputation of metastatic status in men who had not undergone bone imaging and in addition, both T stage and Gleason grades should be included in the model since these factors are also predictive of metastases.

The aim of the above study was to investigate the proportion of men with metastatic prostate cancer in groups defined by T stage, Gleason Grade Group (GGG) and serum levels of prostate-specific antigen (PSA) and if PSA can be used to rule in metastatic prostate cancer all the following analyses were conducted based on the imputed datasets by combining estimates from each completed dataset using Rubin’s rules.

Men with stage T1a-b, i.e. diagnosed at transurethral resection of the prostate, were excluded from further analyses. The proportion of men with metastatic prostate cancer in different PSA levels in metastatic prostate cancer ranges (<20, 20-<50, 50-<100, 100-<300, 300-<500 and >500 ng/ml) was calculated stratified on T stage and Gleason Grade Group. To assess different PSA cut-offs (20, 50, 100, 200, 300, 500, 1000) to predict metastatic prostate cancer we calculated sensitivity and specificity as well as ROC curves, positive and negative predictive value and likelihood ratios.

Likelihood ratios are calculated using sensitivity and specificity to assess if a test usefully changes the probability of a condition in this case presence of metastases. A positive likelihood ratio is defined as the true positive rate divided by false positive rate, whereas the negative likelihood ratio is the false positive rate divided by the true negative rate.

Likelihood ratios range from 0 to infinity with a result of 1 indicating no diagnostic value. A high positive likelihood ratio suggests that metastases are present, while a low negative likelihood test suggests there are few false negative cases compared to true negative cases. Fagan’s nomogram based on positive likelihood ratios for cut-offs 100 and 500 ng/mL were created. The analyses were performed using R 3.4.2.r when combined with T stage and Gleason Grade Group.

Almost all patients present with high serum PSA levels in metastatic prostate cancer, however, progression of prostate cancer can sometimes occur despite a low serum PSA levels in metastatic prostate cancer. Those patients with metastatic prostate cancer and a low serum level of PSA account for less than 1% of all patients with metastatic prostate cancer.

There have been only a few known reports about these patients. In such cases, androgen deprivation therapy (ADT) is relatively ineffective, and the prostate cancer progresses very quickly. Therefore, the prognosis is generally poor compared with the usual metastatic prostate cancer.

Conclusion

In nationwide population-based study, metastatic prostate cancer could not be ruled in with sufficient accuracy by any combination of T stage, Gleason grade and PSA. The best PSA levels in metastatic prostate cancer cut-off for predicting metastases was 500 ng/mL. But however, even for this very high cut-off risk of metastases ranged from 50-94% dependent on T stage and Gleason grade.

All results emphasize the importance of bone imaging in men with advanced prostate cancer for correct staging as a basis for optimal treatment selection. Monitoring the PSA levels in metastatic prostate cancer has created a dramatic shift in the population of patients for whom androgen ablation is initiated. This has resulted in several changing concepts of treatment. Patients with recurrent prostate cancer after the failure of local therapy are now being newly diagnosed with recurrent disease on the basis of a rising PSA levels in metastatic prostate cancer.

The PSA levels in metastatic prostate cancer is the most valuable tool for monitoring disease status and the treatment response, especially in patients with advanced metastatic prostate cancer, as shown in many studies. However, the progression of prostate cancer can sometimes occur in the presence of an undetectable or low serum PSA levels in metastatic prostate cancer.

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