Prostate cancer is cancer of the prostate gland, which is located between the bladder and the penis.
The prostate gland surrounds the urethra, which is the tube that runs from your bladder to the end of your penis and allows urine to exit your body.
The prostate gland secretes various enzymes and proteins that ensure that sperm can move and flow freely.
It is an essential organ in male reproductive health.
Prostate cancer is typically formed of adenocarcinoma cells; these are cancerous cells that develop from glandular tissue.
Prostate cancer can either be localized to the prostate, or it can be metastatic prostate cancer.
Localized prostate cancer: means that the tumor is confined to the prostate gland.
Approximately 90% of all prostate cancers diagnosed in the USA are localized at the time of diagnosis.
Metastatic cancer: this is when the prostate cancer has spread to other parts of the body, such as organs, bones and lymph nodes.
These tend to be far more aggressive and dangerous types of prostate cancer.
Cancers are classified according to which organ they originate in. So even if the prostate cancer spreads to somewhere else in the body, e.g. the lungs or bones, it remains prostate cancer, (it does not become bone or lung cancer).
The 90% of prostate cancers that are localized are more likely to be slow growing cancers.
On average the period in which you have prostate cancer before it is detectable by most diagnostic methods is between 7-14 years.
Prostate cancers rarely change forms, meaning slow-growing prostate cancers will usually remain slow growing.
The editor of a recent annual report on prostate disease from Harvard Medical School, Dr.Garnick, stated that the “[prostate cancers] that are low-grade and indolent are unlikely to cause problems in a man’s lifetime”.
In fact, many men with low grade, slow-growing prostate cancers, outlive or more accurately out-die their prostate cancer. Meaning they die of other natural causes, long before prostate cancer becomes a life-threatening condition.
Currently, there are approximately three million American men in the United States who have been diagnosed with prostate cancer and are still alive today.
How common is prostate cancer?
Prostate cancer is one of the most common types of cancer that can affect men, only skin cancer is more common.
The American Cancer Society estimates that there will be about 174,650 new cases of prostate cancer and 31,620 deaths from prostate cancer in the United States alone in 2019.
The European Journal of Cancer published estimates there will be 450,000 cases of prostate cancer in Europe in 2019.
The median age for being diagnosed with prostate cancer is 66, with 60% of all new diagnoses of prostate cancer being given to men over 65 years old.
Prostate cancer is not just the second most common type of cancer it is the second most common of cancer death for American men. Approximately 1 in 41 American men will die of prostate cancer. These odds are the same for British and European men.
Can I survive prostate cancer?
The odds of surviving prostate cancer are quite good. However, this is mostly dependant on what type of prostate cancer you have.
If you are diagnosed with a slow growing, low grade, and localized prostate cancer; it is likely that you will die of other natural causes, long before your prostate cancer becomes a life-threatening issue.
Prostate cancer survival rates can be broken down by how metastatic and fast-growing the cancer is. Prostate cancer can either be Localized, Regional or Distant.
- Localized: The cancer is contained to the prostate gland and there is no indication that it has spread. (This can include stage 1, 2, and some stage 3 cancers).
- Regional: cancer has spread outside the prostate to nearby organs or lymph nodes. (This mainly includes stage 3B and 4A cancers).
- Distant: cancer has spread to remote parts of the body such as the lungs, bones or liver. (This is normally staged 4B cancers).
For a breakdown and explanation of the stages of prostate cancer click here.
If you have been diagnosed with localized prostate cancer the numbers are reassuring.
The 5-year survival rate for localized or regional prostate cancer is 100%. Moreover, the 10-year survival rate for localized or regional prostate cancer is 98%.
However, despite these reassuring statistics and the research and progress that has been made over the last decade, prostate cancer is still the second leading cause of cancer death among men in the United States.
Approximately 88 men are killed by it every single day.
This is most evident when you look at the 5 survival rate for distant metastatic prostate cancer, (prostate cancer that has spread to other organs, bones or lymph nodes that are far from the prostate gland), the survival rate is only 30%.
What causes prostate cancer?
The exact causes of prostate cancer are still unknown though we have identified some key risk factors that can increase your odds of developing prostate cancer.
There is a strong correlation between your age and your risk of developing prostate cancer. As discussed above, 60% of all new diagnoses of prostate cancer are given to 65-year-old men or older.
However, it is unclear whether or not being older is in and of itself is a factor that increases risk.
Alternatively, if it is a result of having more buildup of metabolic damage caused by having a longer time to make poor dietary, lifestyle, or suffer adverse health events.
There are a few genes that are associated with an increased risk of developing prostate cancer. These may explain why prostate cancer seems to run in some families. However, these genes are likely only to cause a small percentage of prostate cancer cases
Inherited mutations of the BRCA2 gene can increase your risk of developing prostate cancer.
Men with the genetic condition Lynch syndrome (hereditary non-polyposis colorectal cancer, or HNPCC), have an increased risk for a multitude of tumors, including prostate cancer.
The RNASEL mutation has also been linked to increased risk of developing prostate cancer. Normally these gene works to lower your risk of cancer and suppress tumor growth.
However, inherited mutations in this gene seems to let cancerous and abnormal cells live longer than they should. This has been linked to an increased risk of prostate cancer.
The presence of a mutated HOXB13 gene is strongly linked to developing early-onset prostate cancer. This is probably because this gene plays an important role in the development of the prostate gland. While this mutation has been found to run in families it is, fortunately, very rare.
African Americans and Europeans of African or Caribean descent appear to have a far higher likelihood of developing prostate cancer than their white or Asian counterparts. The greater risk seems to be entirely genetic though the exact genes responsible are not known.
According to the Prostate Cancer Foundation (PCF), African-American men are approximately 1.6 times more likely to develop prostate cancer than Caucasian-Americans.
The greater likelihood of developing the disease is also matched by a 2.4 times greater likelihood of dying from the cancer than white Americans.
Though this number may be being affected by environmental factors, such as cost of treatment, dietary differences, and lower quality medical facilities in predominantly African American areas.
There is an increasing body of evidence that diet and lifestyle play a critical role in mitigating prostate cancer risk. This is backed up by the massive difference in the rate of prostate cancer in Western Countries compared to Eastern ones like China, Thailand, and Japan.
There are a number of factors that we should consider.
Firstly, there is a chance that this disparity in prostate cancer rates is genetic. However, there are studies of migrant populations which show quite clear increases in certain diseases like prostate cancer, when ethnic Chinese move to western countries like America.
The change in prostate cancer and in fact in cancer risk rates, in general, seems to move with the generations of immigrants.
The first generation’s diet tends to remain fairly similar to what they ate before they emigrated. But, as each subsequent generation assimilates and their diet moves closer to the Standard American Diet (SAD), we see their risk of prostate cancer normalizing with the western average.
We can also rule out environmental factors such as pollution, as explanations of the east-west cancer divide.
An even bigger difference is seen in highly urbanized Hong Kong, the rate for prostate cancer was approximately four times that in the rest of China – but still only approximately 8 men in 100,000.
The Japanese cities of Hiroshima and Nagasaki have rates of prostate cancer similar to those of Hong Kong: and, both cities were attacked with nuclear weapons so, in addition to the usual pollution-related cancers, one would also expect to find some radiation-related cases of cancer.
It is fairly easy to hypothesize that the fourfold difference in Hong Kong is that Hong Kong is far wealthier and more westernized than the rest of China.
Their diet – especially that of successful and wealthy Hong Kong residents – includes the western quantities of protein, animal fats and most important of all – dairy fats.
In fact, in China, the slang name for breast cancer in Chinese translates as ‘Rich Woman’s Disease’.
It is worth emphasizing that many Asian countries, such as South Korea and Japan, are densely populated and have been highly industrialized and urbanized for many years, yet their rates of prostate cancer remain much lower than in the West.
The even more massive incidence is seen in the UK at around 40 per 100,000. And greater still is seen in the USA at around 110 per 100,000.
A full breakdown of the best anti-prostate cancer diet can be found in the latest edition of our guide to prostate health “All About The Prostate”.
The data suggest that prostate cancer runs in families, above we have already examined the genetic factors that can cause this. However, there is probably an argument for some shared environmental considerations.
Whether or not that is a result of consumption of the same diet, and similarity of lifestyle, or an increased chance of shared exposure to carcinogenic substances is unclear.
What we can say for sure is that if your father or brother had or has prostate cancer than you have twice the risk of the average man of developing prostate cancer in your lifetime.
The risk does not seem to change, for a father or brother, however the risk is much higher if you have several relatives who had prostate cancer.
The age of your relatives also seems to be a factor. Your doctor or oncologist will take a full family history from you.
The age of your relatives when the tumor was first detected is relevant. The younger they were when the cancer was detected the greater your likelihood of developing prostate cancer at some point in your life.
Despite there being a clear genetic and familial risk factor, it is worth noting that, most prostate cancers occur in men without a family history of it.
Benign Prostatic Hyperplasia (BPH)
The medical community is only now coming round to the conclusion that an enlarged prostate, (BPH) is a risk factor for prostate cancer. Medical orthodoxy can take time to change, however, the link is very clear when you examine the research.
There is certainly a strong link between BPH and prostate cancer, and there is a not insubstantial body of evidence that suggests that BPH may in fact be a precursor to prostate cancer.
A study at the Copenhagen University Hospital, Herlev, showed that men with BPH have an increased risk of developing and dying from prostate cancer.
The study found that over 27 years, BPH was associated with a two to three-fold increased risk of men developing prostate cancer, and with a two to eight-fold increased risk of them dying from prostate cancer when compared to men that did not suffer from BPH.
A 2009 study published in the European Journal Of Urology concluded that the “Available data suggest[s] that [a] epidemiologic and pathologic links exist between BPH and PCa” (prostate cancer).
Researchers have looked into the link between the two conditions to try and establish a direct link.
A meta-analysis of observational research found BPH was associated with an increased risk of prostate cancer. The risk was particularly high in Asian BPH patients. 16 case-control studies and 10 cohort studies with 1.6 million participants were included in the analysis. Having BPH increased the risk of developing prostate cancer by 2.9 times. However, the study did not provide the absolute number of patients that had both prostate cancer and BPH.
Other research has reported contradictory findings. For example, a study published found men with smaller prostate sizes were less likely to develop prostate cancer and were less likely to develop aggressive prostate cancer.
Prostate cancer tends to develop in the peripheral zone of the prostate, while BPH usually occurs in the transition zone. Thus some scientists argue that there cannot be a direct link between the two conditions.
Men with BPH are more likely to be making regular visits to a urologist and undergoing prostate cancer screenings. This may explain the link between BPH and prostate cancer. Family history is another strong risk factor that must be accounted for in research studies.
Can you feel if you have prostate cancer?
The short answer is no, you cannot feel if you have a tumor in the prostate. Prostate cancer, especially low-grade prostate cancer is fairly asymptomatic. In fact, some men live for decades with prostate cancer and never even know they have it.
While you cannot feel the prostate cancer, your doctor may be able to detect it during your annual physical. After you reach 50 years old, your doctor may start including a digital rectal exam (DRE), into your normal checkups.
Your doctor will insert a finger into your anus and prod and poke the prostate gland, he is feeling if there are any rough or hard nodules on the surface of the prostate that may indicate prostate cancer.
What are the symptoms of prostate cancer?
If your PSA begins to climb rapidly and approaches or increases over 10 mg/mL it is likely that you have some cancerous cells in your prostate gland.
There are other diagnostic scans you can have if you are concerned about prostate cancer. You can read about them here.
While you cannot feel the presence of prostate cancer, there are a few early warning signs you may want to look out for.
However, these can also be warning signs of BPH, a prostate or bladder infection. So if you do have any of these symptoms, don’t panic, but do talk to your doctor.
- Painful urination.
- Difficulty urinating, or weak flow.
- Night time urination (nocturia).
- Loss of bladder control.
- Blood in your urine (hematuria).
- Blood in your semen.
- Erectile and sexual dysfunction.
- Painful ejaculation.
- Persistent pain that feels like it originates in the bones.
- Increased frequency or easy of fractures and breaks.
- Swelling in your legs and pelvic area.
- Numbness in the feet, legs, and hips.
If prostate cancer has already metastasized to the bones and spine, it can result in additional symptoms.
Again, it’s important to note that these symptoms can also be caused by a variety of conditions, and the presence of any or all of them guarantees the presence of cancer.
What is a Gleason score?
Named after its creator, Dr. Donald Gleason, the Gleason scoring system was developed at a VA hospital in the 1960s and was quickly adopted all over the world as an effective predictor of the pace of prostate cancer growth.
It is now the standard prostate cancer screening used across the world.
The Gleason score is a measurement that is given to indicate the aggressiveness of prostate cancer tumors.
“Aggressiveness” being the medical term used to describe the likelihood of cancer metastasizing.
The higher the Gleason score the greater the risk of your prostate cancer spreading to other organs, bones or lymph nodes.
If prostate cancer does spread to nearby lymph nodes than it can become a more dangerous and life-threatening disease.
They way a Gleason score works is actually fairly simple. Different patterns of prostate cancer cell growth are ranked from 1 to 5.
When your pathologist checks your biopsy samples, they examine your prostate cells under the microscope and will look at the different patterns. The patterns of prostate cancer cells show how quickly and aggressively they are growing.
The lab will then choose the two most commonly appearing patterns and give you a score. The score might look something like this 3+4 = 7.
The first number indicates the most common pattern in all the samples. The second is the second most common pattern. When these two scores are added together, the total is called the Gleason score.
In this example the two most commonly appearing patterns are Gleason 3 and Gleason 4. Meaning that the tumor is primarily made up of cells that fit pattern 3 and, to a lesser extent, cells that match pattern 4. If this is your score, it will be written As Gleason 7 (3+4) or Gleason Score 3+4 = 7.
The order of the numbers is therefore very important since the first score is the most common pattern of prostate cancer cells.
This means that a Gleason score 4+3=7 tumor is thought to be more aggressive and fast-growing than a 3+4=7 tumor.
It is worth noting that patterns 1 and 2 are rarely seen, either because they are hard to distinguish from healthy cells, or because biopsies are rarely conducted on men who would have such low PSA levels and would probably be asymptomatic.
Because patterns 1 and 2 are rarely seen, the lowest Gleason score of cancer normally found on a prostate biopsy is 6 and because the patterns are all scored between 1 and 5, the highest a Gleason can be is 10.
The higher your Gleason score, the greater the likelihood of your cancer spreading outside the prostate.
There are a number of problems with the Gleason score system.
Firstly accuracy, in approximately 20% of cases, the score will be lower than your actual score, since the biopsy misses a higher grade area of cancer.
Or, it is possible for the pathologist to overestimate the aggressiveness of a tumor, and end up with a Gleason score that is higher than it should be.
The second problem is the potential for cancer cells to be spread by the procedure.
Some research has raised concerns that the act of inserting and withdrawing the needles into a prostate cancer that is contained within the prostate gland, could risk spreading cancer. This could happen as the needle is withdrawn.
Finally, some men may be concerned with the fact that a biopsy is a surgical treatment.
However, a biopsy is normally an outpatient procedure done under local anesthetic. And the normal side effects of a biopsy are relatively mild and normally only require a short period of recovery.
Normal side effects of a biopsy can include:
- Bruising around the biopsy site.
- Blood in your pee.
- Short term trouble urinating.
What’s new in prostate cancer research and treatment?
Cancer research is an ongoing process and new studies come out every month. As a result, we see constant small improvements in diagnostics, treatments and survival rates of different types of cancer, including prostate cancer.
What’s new in prostate cancer diagnostics ?
However, in recent years, new diagnostic tests have been developed that work by examining other forms of PSA, or other tumor markers.
Several of these newer tests appear to be more accurate than the older tests, including a PSA test. We would still recommend a regular PSA test as part of your annual checkup.
If you are concerned about the possibility of having prostate cancer, you may want to talk to your urologist about getting one of the newer, non-invasive diagnostic tests done. These tests are:
- The phi test, which combines the results of total PSA, free PSA, and pro PSA to help determine how likely it is that a man has prostate cancer that might need treatment
- The 4Kscore test, which combines the results of total PSA, free PSA, intact PSA, and human kallikrein 2 (hK2), along with some other factors, to help determine how likely a man is to have prostate cancer that might need treatment
- The Advanced Prostate Health Assessment (APHA) is an online questionnaire based on the American urological society guidelines and international prostate symptom score system. It takes 5 minutes to complete the test and while it is not a conclusive indicator of prostate cancer, it can be useful for calculating your level of risk.
- The Progensa test analyzes the level of prostate cancer antigen 3 (PCA3) in the urine after a digital rectal exam (DRE). The higher the level, the more likely that prostate cancer is present. Again this test does not guarantee the presence of prostate cancer or give you any details about the type, size or aggression of the tumor you may have.
- A High-Resolution Color-Doppler Ultrasound scan. This is a new more accurate scan that can see abnormal blood flow that may indicate the presence of a tumor, only some hospitals and clinics are able to perform as it requires specific technologies. It is a non-surgical and non-invasive diagnostic test.
These tests are useful, but you would probably only opt for them if you already suspect that your prostate health is degrading.
If you see no changes on your annual PSA test then your doctor is unlikely to recommend any of these tests.
It is worth noting that there have been some new advancements in the color Doppler diagnostic that may result in it being even more accurate at detecting prostate cancer.
The latest techniques involve injecting the patient with a contrast agent containing microbubbles. This improves the clarity of the ultrasound images, however, very few hospitals are currently offering this test.
Are there any natural treatments for prostate cancer?
For a full breakdown of all of your treatment options for prostate cancer, we would strongly recommend you read our full prostate cancer treatment report.
The report is an 85-page breakdown of the research into the long term quality of life outcomes of the seven most common primary prostate cancer treatments.
We looked at the quality of life and longevity of patients at 5, 10 and 15 years after prostate cancer diagnosis and treatment. The report is written in plain English and designed to be understood by doctors and patients alike.
The purpose of the report is to provide men considering some form of prostate cancer treatment with an unbiased resource to help them make an informed decision.
The report breaks down studies and clinical trials that examine the following treatments for men with prostate cancer:
- Androgen Deprivation Therapy (Hormonal Therapy)
- High Intensity Focused Ultrasound (HIFU)
Ultimately there are no “cures”, natural or otherwise for prostate cancer. There are certain treatments that can put it into remission and there are others that can manage and slow the progression of prostate cancer.
As readers of our report will note, the research is clear that for low-grade prostate cancers there is no difference in longevity amongst patients that opted for treatment and those that opted for active surveillance.
Which, in the case of low-grade prostate cancer may well be preferable to an invasive treatment.
However in the case of advanced prostate cancer or castrate-resistant prostate cancer, (especially if it is metastatic castration-resistant prostate cancer) you may wish to opt to for a more immediately to treat prostate cancer.
In cases of early prostate cancer and advanced prostate cancer you may wish to consider making significant dietary and lifestyle changes for your health.
There is some research that shows that a high-fat diet, such as the ketogenic diet may increase survival rates for prostate cancer.
Boron and Prostate Cancer
The research shows that consuming adequate boron levels are associated with a 64% reduced risk of prostate cancer.
However, obtaining protective levels of boron from food alone is difficult.
Nutritional research shows that the western diet is low in Boron. This means that supplementation with low-cost boron could be an effective way for men to lower their risk of prostate cancer.
A 2001 study on the diet of prostate cancer patients that compared the diets of seventy-six prostate cancer patients with those of 7,651 men without prostate cancer.
The study found that the men who ingested the greatest amount of boron from their diets were 64% less likely to develop prostate cancer than those who consumed the least.
There have been further studies that have confirmed similar results. One such study compared the dietary intake of boron in ninety-five prostate cancer patients with that of 8,720 healthy male controls. That study was controlled for many other factors.
They too found that men with the highest boron consumption showed a 54% lower risk of prostate cancer compared to those with the lowest intake. This seems to confirm that a decrease in prostate cancer risk is directly proportional to the amount of boron that you consume.
Research into whether or not boron supplements have an effect on prostate cancer found that oral administration of boron-containing supplements substantially decreased tumor size. It also lowered levels of prostate-specific antigen.
In an animal model, researchers orally administered various concentrations of a boron-containing solution to test subjects and found that this resulted in a decrease in prostate tumor size of 25% to 38%.
Remarkably, PSA levels dropped by an astounding 86% to 89% in the animals that received boron.
More research into the impact of Boron on prostate cancer, osteoporosis, and general health can be found in this article.
Another natural nutrient that has been studied extensively in recent years is vitamin D. Research has found that high levels of vitamin D seem to lower your risk of developing certain, more aggressive types of prostate cancer.
Another 2012 study, that looked at the links between vitamin D and prostate cancer progression, came to the conclusion that men with low-risk prostate cancer may benefit from Vitamin D3 supplementation.
In a year-long study where men with low-risk prostate cancer were given a year of vitamin D3 supplementation.
PSA serum levels were measured at entry and every 2 months for 1 yr. Biopsy procedures were performed before enrollment (for eligibility) and after 1 yr of supplementation.
In terms of safety, the study found no adverse events associated with vitamin D3 supplementation were observed. 55% of participants showed a decrease in the number of positive cores or decrease in Gleason score.
What is Active Surveillance?
Active surveillance is used to monitor localized, early prostate cancer, instead of treating it straight away with surgery or radiotherapy. It involves having regular tests to keep an eye on the cancer through tests like MRIs, biopsies or PSA tests.
Treatment is only opted for if the cancer prognosis changes or the cancer spreads. This helps to avoid or at least delay the side effects associated with treatments.
Although some men worry about not having treatment and their cancer spreading, many men can easily get on with their daily lives between check-ups without any noticeable changes to their day to day routine, this is because low grade or early prostate cancer is largely asymptomatic.
Many of the men who opt for active surveillance will not need treatment during their lifetime.
Research shows that men who undergo active surveillance have the same chance of living for 10 year or longer as men who undergo radiotherapy or surgery, but with fewer and less intense side effects.
A different study found that all treatments had worse effects on a patient’s quality of life than active surveillance.
40% of men who had opted for Androgen deprivation therapy (ADT) experienced some form of urinary leakage, as did; 33.9% of radiotherapy patients and, 62% of radical prostatectomy.
However, only 12% of men who opted for active surveillance reported any urinary leakage and this could largely be attributed to untreated BPH.
Another study by Punnen et al. showed that men who chose active surveillance were less likely to suffer from sexual dysfunction than men who underwent any form of prostate cancer treatment. Only 23% of the active surveillance group reported any sexual dysfunction.
Whereas the number of men reporting sexual dysfunction ranged from 38% to 68% in the various treatment groups.
Additionally, men who opted for active surveillance men also reported lower levels of urinary dysfunction than men who had undertaken a surgical treatment.
Another study conducted at 5 years after the initial treatment compared the effects of radical prostatectomy to active surveillance. The study found that erectile dysfunction impacted 80% of the men that had undergone radical prostatectomy, but only 45% of men of the men undertaking active surveillance.
Also, a greater proportion of men who underwent radical prostatectomy suffered from urinary incontinence, with 49% of radical prostatectomy reporting urinary leakage compared to only 21% in the active surveillance group.
These studies show that overall active surveillance has fewer side effects than surgical and non-surgical treatments for prostate cancer.
Active surveillance has shown to have fewer side effects than both surgical and non-surgical treatments and is probably preferable whenever it is suitable.
Additionally, some studies suggest that the treatment options themselves do not necessarily elongate life expectancy.
These findings combined with the severe nature of the side effects of the treatments may explain the recent increase in the percentage of American men who opt for active surveillance.
The best protocols for active surveillance
At the beginning of the active surveillance period there are 5 separate, non-invasive tests that you may wish to get to give you the most accurate picture on the state of your prostate cancer.
These tests are:
You should do a full battery of tests at the beginning of the active surveillance to allow you to establish a baseline. This should establish where the cancer is? How big is the tumor? How aggressive is the cancer?
All future tests are then measured against the original tests. This allows you to track the progression of the tumor, and decide if you ever need to opt for a treatment.
During the first year, you should take a PSA test every 4 months along with a Digital Rectal prostate exam. After 12 months you should have another MRI and Color Doppler Ultrasound.
We would also recommend that you keep a daily prostate health diary. Which, is a journal of your symptoms, such as frequency of nighttime bathroom trips or urinary issues.
A sudden worsening of your symptoms can indicate a change in your prostate cancer.
From the second to the fourth year of active surveillance you should have PSA tests every six months, and the scans every 12 months.
After you have been on active surveillance for more than five years, you can change to have a PSA test as part of your annual checkup and have the scans every other year.
Prostate cancer is a serious disease that affects men’s health, so it is very important to begin taking steps now to reduce your risk. The good news is that it is treatable.
Any man diagnosed with prostate cancer should be sure to seek information on possible treatments as well as a second or even a third opinion from professionals with no ties to the diagnosing clinician.
Studies have shown that due to the usual slow progression of prostate cancer, time spent evaluating the conditions and treatment options does not interfere significantly with later treatment and overall prognosis.