Biomarkers For Prostate Cancer In Active Surveillance
The use of biomarkers has expanded in recent years as an additional method for refining risk stratification in select patient populations. In particular, identifying mutations in the BRCA2 gene can help prevent adverse outcomes. BRCA2 gene mutations have been associated with worse outcomes on AS, prompting the need for closer monitoring for these at-risk patients when enrolled in AS cohorts .
Studies have evaluated the short-term effects of using tissue-based molecular biomarkers alongside routine clinical indicators, although prospective long-term outcomes of using biomarkers in AS populations have not been evaluated . Data suggests that these tissue-based assays can be utilized in prostate cancer patients with higher volume Grade Group 1 or favorable intermediate risk Grade Group 2 to help guide clinical decision making and provide more data for determining a management protocol . However, at the present time, tissue-based biomarkers have not been recommended for routine use and should not be used for patients who have clear clinical indications for either an AS protocol or immediate active treatment .
Detailed pathology may also be informative to help determine risk. There is growing evidence that presence of invasive cribriform and/or intraductal carcinoma portend a poorer prognosis, and have therefore been proposed as exclusion criteria for AS . However, this remains unproven.
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Surgery to remove the prostate, a sexual gland, is a long and bloody operation that carries high risks of erectile dysfunction and incontinence. Radiation therapy, an alternative approach, can come with side effects such as frequent urination and burning, diarrhea, and rectal bleeding.
Active surveillance, I was told, would let me avoid the side effects of surgery and radiation while maintaining normal sexual and urinary function without jeopardizing my survival Klotzs research and studies that followed showed that men who chose active surveillance had the same 10-year survival rate as those who had surgery or radiation.
This management strategy for prostate cancer basically entails one or two PSA blood tests per year, an MRI every few years, a prostate biopsy every two to five years and, in some men, especially those with intermediate prostate cancer who are on the fence between active surveillance and surgery, tests of genetic markers that can predict how aggressive a cancer may be, which can tip the scales on choosing active surveillance or surgery or radiation therapy.
Even though the first urologist pushed the panic button, choosing active surveillance was a no-brainer for me because the research showed it was a safe approach that avoided the sexual and urinary side effects and had the same 10-year survival as surgery or radiation. Why bother, I figured, with aggressive treatment when it added nothing to longevity?
When Is It Time To Stop Being Checked For Prostate Cancer
Its essential to be fully informed about the potential risks of PSA testing, which includecomplications from biopsies and teratments.
The answer depends on your current health and your level of concern about cancer.
Routine PSA testing to check for prostate cancer is no longer recommended for most men. But despite what the experts suggest, many men continue to opt for annual PSA tests. This includes a surprisingly large number of men in their 70s. In a recent study in the journal Cancer, more than half of a group of men 75 and older had PSA tests and biopsies.
These men have placed their hope in the value of early diagnosis and treatment, yet stand to gain less from PSA testing than younger men. Across all ages, routine PSA screening leads to life-saving treatment for cancer in about one in every 1,000 men screened.
Force guidelines: These independent experts on preventive medicine do not recommend PSA screening for prostate cancer in men at any age, due to a lack of definitive evidence that the benefits of PSA testing are greater than the risks.
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Finding A Friend Who Understands
Unfortunately, in March 2021, Bobbys three-year biopsy revealed that although his cancer was still small and confined to the prostate, the grade had increased. He would need treatment. He met with MSK radiation oncologists and proton therapy experts to learn about his treatment options but decided to have surgery with Dr. Ehdaie.
Because Dr. Ehdaie is such a strong believer in active surveillance, when he told me I needed treatment I knew I could trust his judgment, Bobby says. To me, it gave him more credibility.
When Bobby was reading about where to go for prostate cancer treatment, he was inspired by a story on MSKs website about Mike Rodgers, a marathon runner and triathlete diagnosed with prostate cancer whod had surgery with Dr. Ehdaie. Bobby reached out to Mike to learn more about his experience. It turned out that the two lived near each other, and Mike invited Bobby to join his Tuesday morning track club. They became good friends.
Before his surgery, Bobby was already an active runner and in good shape. However, once he knew that he would need treatment, he ramped up his workouts. He ran multiple half-marathons and other races to get out of his comfort zone. I called it pre-hab, he says. I knew that surgery would be really hard on my body, so I wanted to be prepared. A month before surgery, at Mikes suggestion, he transitioned from running to focusing on adding muscle and working on his core.
Who Should Choose Active Surveillance
Some of the characteristics that might qualify you for Active Surveillance include grade group 1 or Gleason 6, a PSA level < 10, cancer that is confined to the prostate, and/or cancer that is very low volume when biopsied.
The ideal candidate for Active Surveillance has low-risk prostate cancer. Learn more about Risk Groups.
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How Is Prostate Cancer Monitored
Although health organizations have issued guidelines for how men on active surveillance should be followed, theres no consensus on the ideal active surveillance management strategy.
In general, active surveillance includes:
- Periodic prostate-specific antigen blood tests.
- Digital rectal exams.
- Prostate biopsies.
Many experts, including Dr. Haywood, also incorporate advanced genomic testing and magnetic resonance imaging with targeted biopsy into their active surveillance programs.
Until recently, we havent really had the tools to assess an individuals change in biology in real time. Now, MRI and targeted biopsy and genomic testing should allow us to do that.
The types and times between when these tests should be done vary, depending on the volume and aggressiveness of your cancer, your age and other individual characteristics. Whatever strategy your physician uses, its vital to return for follow-up testing.
But in one study, researchers reviewing registry data on more than 2,200 patients reported that within two years of being on active surveillance, about 1 in 10 of the men stopped following up.
Additionally, in a study presented at the American Society of Clinical Oncology annual meeting in June 2019, researchers noted that among 346 men on active surveillance, only about one-third followed guideline-recommended monitoring
Playing With A Loaded Gun
It was the concern about overtreatment that originally encouraged wider adoption of AS. Now, there is a different concern as newly available 5+ year data suggests that some urologists keep men on AS beyond the window for curative treatment. Without diagnostic certainty about which cell line is growing in a mans body, there is always the possibility that hes harboring a disease that does not generate a high PSA but which has the capability to progress rapidly, spread beyond the gland and become lethal. In this respect, AS is like playing with a gun that holds an unknown bullet.
Tosoian et al. assembled data from various published AS studies. Within 5 years of starting AS, the proportion of men who are upgraded by biopsy and receive whole gland treatment ranges from 24-50%. Of four studies that followed treated patients, biochemical recurrence ranged from 8-25% one particular study reported biochemical recurrence rates of 7% at 2 years and 15% at 5 years. Biochemical recurrence means tumor cells had already left the gland at the time of surgery/radiation and are now multiplying locally, regionally, or distantly.
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Feeling Ecstatic After A Successful Surgery
On July 27, Dr. Ehdaie performed Bobbys robotic surgery at MSKs Josie Robertson Surgery Center. Within hours, Bobby was walking laps around the floor. He was ready to go back to work after only a few days, but his wife insisted that he wait a little longer. Within two weeks, though, he was back at his office running his courier company.
He also headed back to the track almost immediately, walking with trekking poles until he felt stronger. On Bobbys 60th birthday, six weeks after his surgery, he met his track club at 6:00 a.m., and they ran six miles together. Five days later, he ran a ten-mile race, finishing fourth in his age division and in the top 25% overall.
Dr. Ehdaie points out that Bobbys recovery has been unusually fast, and explains that every patients recovery is different. Bobby is the poster child for active surveillance, because hes seen both sides of it, he adds. He was able to delay treatment for many years, and then when his cancer changed, we were able to offer him a successful surgery.
I have so much energy now, and almost no pain. Im ecstatic, Bobby says. The side effects that I feared were minimal and short lasting. At his follow-up appointment, Bobby learned that his PSA level was undetectable. He was cancer free. He is already back to training for several races in October and November.
A Number Of Men May Stop Active Surveillance For Prostate Cancer
Transition to definitive treatment more likely for patients with additional accompanying medical conditions
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Does My Age Influence Whether Active Surveillance Is The Right Choice For Me
Younger men will live longer with their cancers, and thus have a higher likelihood that their cancer could progress. However, younger men whose cancers appear to be less aggressive may be able to stay on Active Surveillance longer. Younger men also have more to lose when it comes to quality of life as they often have better erectile and urinary function than older men.
Active Surveillance may also be more appropriate for men who are currently battling other serious disorders or diseasessuch as significant heart disease, long- standing high blood pressure, or poorly controlled diabetes. In a patient with other health issues, the patient and his doctors might feel that performing invasive tests or treatment would cause more harm than benefit. For these men, their treatment plan would of course help manage any symptoms that occur due to advanced disease. There are also some men with favorable intermediate risk who may be good candidates for Active Surveillance.
Some physicians also administer commercial genetic testssuch as Decipher®, ProMark®, and Prolaris®that may be helpful in determining if you are a good candidate for Active Surveillance. Researchers are working to define the best ways to use these tests.
Natural History And Genetic Features Of Low
The chief dilemma in managing clinically localized prostate cancer stems from the heterogeneity of the disease. Prostate cancer arises from genetically altered prostate epithelium and slowly progresses over several decades. Given its features of multifocality and tumor heterogeneity, the course of prostate cancer is difficult to predict. Men may live their entire natural life without having any symptoms from prostate cancer. Zlotta et al confirmed this hypothesis when they prospectively compared tissue obtained during autopsy from prostate glands in both a Caucasian and an Asian population. Prostate cancer was found in a similar proportion of men in both groups. Also, more than 50% of the cancers in the Asian group had a Gleason score of 7 or greater. The natural history of this disease, which is characterized by slow progression, makes it possible for active surveillance to be an effective management strategy.
The key point here is that most Gleason 6 cancers have innocent genetic features and no risk of metastasis. Thus, in the absence of higher-grade cancer, there is little indication for treatment in most patients.
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Treating The Anxiety Not The Cancer
Unlike Bobby, some patients are not sure they want to avoid treatment, even if they can do so safely. Christian Nelson, Chief of the Psychiatry Service in MSKs Department of Psychiatry and Behavioral Sciences, studies the anxious feelings surrounding active surveillance and why it is so difficult for some people to accept the fact that its better for cancer to remain in their bodies.
Dr. Nelson recently completed a study that found men who score higher on tests to detect anxiety and depression are more likely to choose treatment than active surveillance. Just hearing the word cancer is obviously scary and anxiety-provoking, he says. Its important to understand how these feelings affect the decision-making process. For patients who have a lot of anxiety, there are many ways to reduce it.
Dr. Eastham points out that treatment for prostate cancer can have a lot of side effects, including changes in bladder, bowel, and sexual function. I like to say, only half-joking, that having radiation or surgery is not the best treatment for anxiety, he notes.
How Is Active Surveillance Done
Although the protocol can vary, recommendations for active surveillance generally call for routine PSA tests and prostate biopsies to check for any indication that the cancer might be growing.
For example, patients at Montefiore Health System in New York City get a PSA test every 36 months, at least initially, and an MRI-guided biopsy a year after diagnosis, said Kara Watts, M.D., a urologist at the hospital who specializes in treating prostate cancer but was not involved in the study.
After the initial PSA tests and biopsy, how often they are performed depends largely on the patients particular situation, Dr. Watts explained.
We have a flexible protocol, particularly for people at both ends of the spectrum, she continued. For a man in his 70s and a life expectancy of 510 years , she said, additional PSA tests or biopsies may only be conducted every few years or only if he has symptoms. An otherwise healthy man in his 50s, on the other hand, will usually continue to have PSA tests and MRI-guided biopsies on a schedule similar to the initial protocol.
At the NIH Clinical Center, where Dr. Parnes sees patients, in addition to routine PSA testing, MRI-guided biopsies are used to help inform decisions around whether to pursue active surveillance and as part of the surveillance protocol.
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What Is Active Surveillance Or Watchful Waiting
Some prostate cancers are slow growing and might never cause you problems.
Your doctor might suggest waiting and seeing whether the cancer develops, rather than giving treatment straight away. All cancer treatments have side effects. So monitoring your cancer can help make sure you don’t have treatment that you don’t need.
You have regular tests to check whether the prostate cancer is staying the same size or starting to grow. You can start treatment if there is any sign that your cancer is beginning to change or grow.
More Active Surveillance But Not Enough
To conduct their study, Dr. Cooperberg and his colleagues looked at data from all men newly diagnosed with prostate cancer in the AUA Quality Registry. This registry collects real-time data from more than 240 participating US urology practices and more than 2,100 urologists.
Overall, of the more than 84,000 patients covered by the study, 20.3% were diagnosed with low-risk disease. The number of men diagnosed with low-risk disease actually fell during the study period, from about 24.6% in 2014 to 14.0% in 2019. That finding is consistent with other recent studies showing a decline in low-risk diagnoses, which researchers have attributed to fewer men being screened via PSA testing.
But even as diagnoses of low-risk disease have dropped, more men with low-risk disease are opting for active surveillance, Dr. Cooperberg reported. In 2014, 26.5% of men with low-risk prostate cancer chose active surveillance. By the end of 2021, 59.6% did.
Rates of active surveillance also increased among men diagnosed with intermediate-risk prostate cancer, which is considered to have a modestly greater likelihood than low-risk prostate cancer of progressing to the point where it could be fatal.
The variability in the use of active surveillance is alarming, Dr. Parnes said. It likely reflects, at least to some degree, entrenched patterns of care among some urologists. For some, I suspect their feeling is, I treat cancer, and this is cancer. Im not having this conversation , he said.
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Men Undergoing Active Surveillance For Prostate Cancer Which Can Avoid Or Delay Unnecessary Treatment Should Have Their Prostate Specific Antigen Levels Measured Every 3
08 January 2014
Men undergoing active surveillance for prostate cancer, which can avoid or delay unnecessary treatment, should have their prostate specific antigen levels measured every 3-4 months initially, according to updated guidelines from NICE.
Prostate cancer is among the most common cancers in men, making up more than a quarter of diagnoses and accounting four seven per cent of cancer deaths.
Around 37,000 men are diagnosed each year, and while it mostly affects older men, men under 65 can be affected too. Men from a black African-Caribbean family origin are also three times more likely to develop the disease than white Caucasian men.
Among the updated recommendations, is a new protocol for active surveillance. This is a way of monitoring slow-growing prostate cancers that might never progress or cause any symptoms, and can help avoid or delay treatment such as radiotherapy or surgery which might otherwise be unnecessary.
NICE recommends that doctors should offer active surveillance for men with low-risk localised prostate cancer for whom radical prostatectomy or radical radiotherapy is suitable.
The protocol recommends measuring PSA levels every 3-4 months in the first year of surveillance, and then at increasing intervals if there is no evidence of disease progression.
Active surveillance should not, however, be offered to men with high-risk localised prostate cancer.