Recurrence after treatment


Rev B

Index : Recurrence of Prostate Cancer

Topic                                                                                Paragraph Number

Introduction 1.0
Definition of, and reason for Recurrence 1.2, 1.3
Discussion 2.0
Frequency of, and when Recurrences start 2.1, 2.2, 2.3, 2.4, 2.5
Definition of, and reason for Recurrence 1.2, 1.3
Factors that Effect Recurrence 2.6, 2.7, 2.8, 2.9, 2.10, 2.11, 2.12, 2.13, 2.14
Procedure to Slow a Recurrence 2.15
Comments 3.0
Incorrect Treatment 3.1
Other Considerations 3.2
Recurrence does NOT mean death 3.3
Salvage treatment 3.4
References 4.0


1.1 Introduction
This segment discuses something that no patient thinks about, and no doctor wants to discuss,  namely a recurrence of your cancer after treatment Unfortunately, this situation occurs about 40 to 50 percent of the time, for men even with low and moderate prostate cancer.
The reader will learn why this occurs, and hopefully what may be done to avoid this situation, if at all possible. Therefore, he must consider whether it is better to be treated, or select a different treatment, a more encompassing aggressive treatment. In a huge number of cases it is also possible to delay treatment, because, delayed treatment has the same outcome as immediate treatment for low grade prostate cancer cases. The only difference is the lack of side effects from not being treated.


1.2 Definition of, and reason for Recurrence:
Recurrence means that the first treatment did not cure you.  Sometimes one or more treatment do not stop the cancer, and further treatment modalities will be prescribed. If the cancer continues after a  treatment modality, you have a recurrence of your cancer. Advanced treatment may be necessary, and you should be under the care of a Medical Oncologist specializing in PC.
A recurrence does not mean that the doctor who treated you did a poor job, although it is possible that you received an inappropriate treatment.


1.3 Reason for Recurrence
At the time of detection, the PC may no longer have been confined to the prostate capsule. If the cancer has progressed into the area surrounding the prostate (The Fossa), the doctors may not know this. He may think your cancer is confined, and after a radical prostatectomy, often states “We got it all” based on a pathology report stating you had negative margins. This is his hope, as he is trying to be positive, but there is no way of knowing this. Only time will tell.
The reason is that for many years prior to detection, microscopic cancer cells may have spread thru the blood system. These cancer cells are too few to be detected at the time of diagnosis or  treatment, however within about two to five years these cells multiply, and generate sufficient PSA to be detected, indicating a recurrence. This occurs in about 40% to 50% of the men who are treated, regardless of the treatment modality (R1002), and regardless of what any doctor may say.
If the cancer has spread further into the body, very often a high PSA and / or high Gleason Score will be observed, but these indications may not always occur. This is why PC is so dangerous.
When the cancer microscopically spreads it may be to local or distant sites within the body. Locally means to the prostatic bed around the prostate.(Fossa). Distant means to other body organs, and / or the bones.
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2.0  Discussion


2.1 Frequency of, and when Recurrences start
Rarely mentioned, but a terrible fact is the huge recurrence rate after PC treatment.  The National Cancer Institute says approximately 40 to 50 percent of men with low to moderate grade PC will have a recurrence within about five years  R1001, R1004, and R 1005
The Mayo Clinic in Rochester, Minnesota reported that about 200,000 men who had been treated for prostate cancer learn each year, sometimes too late, that their malignancies have returned. Ref: R732.  My prostate cancer support group has many men who have had a recurrence, who were told  their initial treatment was a success.
Recurrences occur even if you are told “your prostate cancer was contained” or “we got it all.” This leads men to falsely believe that they are cured. R1002 and R1003

2.2 “As a practical matter, most men who are likely to develop recurrent PC do so within 4 to 5 years. After radiation or a radical prostatectomy” The PSA doubling time is a good indicator of recurrent PC. Reference: Prostate Forum  Vol 5 Number 9

Recurrence as function of PSA

Study Finds New Way to Pinpoint Dangerous Prostate Cancer  by Maggie Fox 1/12/ 2017.
Researchers say they’ve found a new way to tell if a man’s prostate cancer will come back and kill him after treatment.
If a blood test called a PSA doesn’t fall to low enough levels after treatment, it means the cancer’s not all gone and will likely come back and spread, the team at Brigham and Women’s Hospital and Harvard Medical School reported. PSA tests look for prostate specific antigen, a protein made only by prostate cells. Higher PSA levels suggest that prostate cells are growing — often because of cancer, but sometimes if the prostate is inflamed or because of the harmless enlargement of the prostate that comes with aging.
The important number to know: PSA should fall to 0.5 nanograms (ng per ml) or lower. That gives doctors a chance to act right away, said Dr. Anthony D’Amico, the senior oncologist on the study. “Instead of waiting to see if PSA has gone up, this can tell you that somebody has not only failed treatment, but failed so badly that they are going to die of prostate cancer,” D’Amico told NBC News. “You should know what your PSA is after your treatment. You need to know once it stops going down if that low point is above half a point (0.5).”

“By identifying and enrolling these men in clinical trials immediately, the hope is to take a prostate cancer that appears to be incurable and make it curable” added Dr. Trevor Royce, who led the work on the study. It’s an important question.

Prostate cancer is very common, showing up in 240,000 U.S. men every year. It kills about 30,000 a year. In most men, prostate cancer isn’t likely to kill them before something else does. But since prostate cancer still kills so many men, it’s important to find out which men are most at risk of dying early. This new study shows that PSA can tell you.

PSA’s not a very good indication of cancer, but it’s a good measure of how well cancer treatment has worked. PSA should drop to very low levels after surgery or radiation treatment for cancer. But it doesn’t always, and it often rebounds. “Normally, a man gets treated for prostate cancer and his PSA is monitored every six months for a few years. In order to call somebody a failure, that the disease has recurred, you need to see a PSA that is going up.” But not every man whose PSA goes up after treatment dies of cancer. And not every prostate cancer patient is saved by fresh treatment once his PSA rises to a certain level, usually a reading of 10.

The Harvard team wanted to see if there’s a more precise way to tell who had the more dangerous cancer. They studied 157 men treated for prostate cancer, watching them for more than 16 years on average. Most — 70 percent — died by then. “Men were seen in follow-up every three months for two years, every six months for the subsequent three years, and every year thereafter,” the team wrote in their report, published in the Journal of the American Medical Association’s JAMA Oncology.

The main determinant of whether the men would die, the team found, was how low their PSA level fell. If it did not drop to 0.5 after treatment, the men were most likely to have the cancer come back and kill them, D’Amico said. “If it doesn’t drop below this half point in follow-up … you know that person not only has residual prostate cancer, but the type of prostate cancer that often goes on to kill them,” D’Amico said.

Just having PSA levels rise again was not a very good predictor of whether the men would die, the team found. Now doctors need to see if treating these men right away, instead of waiting for their PSA levels to rise more, may save them, D’Amico said. “Before, we saw this number and said ‘gee we are concerned but let’s watch,’” he said. Now doctors can act.

There are many drugs that prostate cancer patients can get, but they’re almost never given until the cancer’s come back and started causing symptoms.

“You know that person not only has residual prostate cancer, but the type of prostate cancer that often goes on to kill them.” “These are treatments that are used when a man has metastatic disease. They have been shown to prolong life but not to cure it,” D’Amico said.

It might be if a patient gets such treatment right away, he could live even longer or perhaps even be cured. But a study will have to be done to show it. The men in the study had radiation or hormone therapy, but D’Amico said the finding should hold for men who have had their prostates surgically removed, also.

“You should know what your PSA is after your treatment. You need to know once it stops going down if that low point is above half a point (0.5),” D’Amico said.

http://www.nbcnews.com/health/health-news/study-finds-new-way-pinpoint-dangerous-prostate-cancer-n706151

2.3 “Up to 40% of men who undergo a radical prostatectomy, will have a recurrence within five (5) years” said Carolyn Lamb, MD at the Mount Auburn Hospital Support Group.

2.4  A study by the School of Medicine, Washington University, in 2004, deduced that the recurrence rate for men who were treated was 32 percent in 10 years. (J Urol 2004 Sep;172 (3): 910-4).
The problem with this is that they used a Kaplan-Meier Mathematical Analysis. Why not look at the medical records of actual patients.  I say that the recurrence rate is about 40 percent within five (5) years. My data comes from people at the National Cancer Institute, speaking with various physicians in the field of PC treatment and research, and observing over 3500 men in my PC support group. BEWARE of MATHEMATICAL ANALYSES   make 2.4

2.5 The Department of Urology, Vita-Salute University San Raffaele, Milan, Italy reported that up to 40% of patients develop a biochemical recurrence which can be either a local or distant recurrence of prostate cancer.  R356

Dr Otis Brawley, Chief Medical and Scientific Officer and Executive Vice President of the American Cancer Society. was quoted in the New York Times on April 4, 2002, as saying that 40 percent of men will have a recurrence within two (2) years 

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2.6 Factors that Effect Recurrence.

New Way to Pinpoint Dangerous Prostate Cancer R1187

Study Finds New Way to Pinpoint Dangerous Prostate Cancer  by Maggie Fox 1/12/ 2017.
Researchers say they’ve found a new way to tell if a man’s prostate cancer will come back and kill him after treatment.
If a blood test called a PSA doesn’t fall to low enough levels after treatment, it means the cancer’s not all gone and will likely come back and spread, the team at Brigham and Women’s Hospital and Harvard Medical School reported. PSA tests look for prostate specific antigen, a protein made only by prostate cells. Higher PSA levels suggest that prostate cells are growing — often because of cancer, but sometimes if the prostate is inflamed or because of the harmless enlargement of the prostate that comes with aging.
The important number to know: PSA should fall to 0.5 nanograms (ng per ml) or lower. That gives doctors a chance to act right away, said Dr. Anthony D’Amico, the senior oncologist on the study. “Instead of waiting to see if PSA has gone up, this can tell you that somebody has not only failed treatment, but failed so badly that they are going to die of prostate cancer,” D’Amico told NBC News. “You should know what your PSA is after your treatment. You need to know once it stops going down if that low point is above half a point (0.5).”

“By identifying and enrolling these men in clinical trials immediately, the hope is to take a prostate cancer that appears to be incurable and make it curable” added Dr. Trevor Royce, who led the work on the study. It’s an important question.

Prostate cancer is very common, showing up in 240,000 U.S. men every year. It kills about 30,000 a year. In most men, prostate cancer isn’t likely to kill them before something else does. But since prostate cancer still kills so many men, it’s important to find out which men are most at risk of dying early. This new study shows that PSA can tell you.

PSA’s not a very good indication of cancer, but it’s a good measure of how well cancer treatment has worked. PSA should drop to very low levels after surgery or radiation treatment for cancer. But it doesn’t always, and it often rebounds. “Normally, a man gets treated for prostate cancer and his PSA is monitored every six months for a few years. In order to call somebody a failure, that the disease has recurred, you need to see a PSA that is going up.” But not every man whose PSA goes up after treatment dies of cancer. And not every prostate cancer patient is saved by fresh treatment once his PSA rises to a certain level, usually a reading of 10.

The Harvard team wanted to see if there’s a more precise way to tell who had the more dangerous cancer. They studied 157 men treated for prostate cancer, watching them for more than 16 years on average. Most — 70 percent — died by then. “Men were seen in follow-up every three months for two years, every six months for the subsequent three years, and every year thereafter,” the team wrote in their report, published in the Journal of the American Medical Association’s JAMA Oncology.

The main determinant of whether the men would die, the team found, was how low their PSA level fell. If it did not drop to 0.5 after treatment, the men were most likely to have the cancer come back and kill them, D’Amico said. “If it doesn’t drop below this half point in follow-up … you know that person not only has residual prostate cancer, but the type of prostate cancer that often goes on to kill them,” D’Amico said.

Just having PSA levels rise again was not a very good predictor of whether the men would die, the team found. Now doctors need to see if treating these men right away, instead of waiting for their PSA levels to rise more, may save them, D’Amico said. “Before, we saw this number and said ‘gee we are concerned but let’s watch,'” he said. Now doctors can act.

There are many drugs that prostate cancer patients can get, but they’re almost never given until the cancer’s come back and started causing symptoms.

“You know that person not only has residual prostate cancer, but the type of prostate cancer that often goes on to kill them.” “These are treatments that are used when a man has metastatic disease. They have been shown to prolong life but not to cure it,” D’Amico said.

It might be if a patient gets such treatment right away, he could live even longer or perhaps even be cured. But a study will have to be done to show it. The men in the study had radiation or hormone therapy, but D’Amico said the finding should hold for men who have had their prostates surgically removed, also.

“You should know what your PSA is after your treatment. You need to know once it stops going down if that low point is above half a point (0.5),” D’Amico said.

http://www.nbcnews.com/health/health-news/study-finds-new-way-pinpoint-dangerous-prostate-cancer-n706151

2.7 Researchers at Memorial Sloan-Kettering Cancer Center, New York, investigated the significance of a patient’s reaching a certain PSA level at a specific point in time after external beam radiation therapy.
They found that patients with a PSA value of less than or equal to 1.5 at two years had a 2.4 percent incidence of distant metastases at five years after treatment and a 7.9 percent incidence at 10 years after treatment. Patients with a PSA value higher than 1.5 experienced a significantly higher rate of metastases at five and 10 years after treatment (10 percent and 17.5 percent, respectively). Ref: The Walter Reed Army Medical Center (WRAMC)  Feb. 2010, page 4

2.8 A recurrence can, and too often does, occur regardless of the Gleason Grade, but the higher the Gleason Grade the  more likely the shorter the time to recurrence (R203). One factor that is considered is the Tertiary Gleason Grade of the cancer in the pathology report. If the pathologist detects a Gleason Grade of 5 in more in five (5) percent of the prostate tissue, he will usually mention it as this consideration of a third (tertiary) pattern may provide additional prognostic information. Often the Gleason Score will be up-graded by one unit.  A Gleason Grade of 7 will therefore be considered a Gleason Grade of 8, and should be treated as such. Should less than 5 percent of the sample have a Gleason Grade of 5, the Gleason Score will usually not be considered in the treatment.
This study reported the following median times to recurrence:  The median time to PSA failure (the time by which half the men had experienced a PSA failure) was 15.4 years among men with a Gleason score of 6 or less; 6.7 years among men with a Gleason score of 7 without tertiary grade 5; 5.0 years among men with a Gleason score of 7 with tertiary grade 5; and 5.1 years among men with a Gleason score of 8 to 10.

2.9-PSADT Unreliable For Predicting Prostate Cancer Worsening.    MILAN—PSA doubling time (PSADT) is not a reliable predictor of disease progression in men with low-risk prostate cancer who are on active surveillance (AS), according to a new study presented at the 28th annual congress of the European Association of Urology.
Frederick B. Thomsen, MD, and colleagues at the University of Copenhagen in Denmark reported on the study of 258 PCa patients on AS.  After a median of 1.2 year, 68 (26%) of 258 subjects underwent radical prostatectomy after meeting progression criteria. The researchers found no association between PSADT during AS and outcome.  R737

2.10Some of the references state that the PSA Doubling Time (PSADT) is a good indicator of a recurrence.  A newer study in March 2013 (Ref R737), claims that the PSA is not a reliable predictor of disease progression in men with low-risk prostate cancer.

According to Dr Marc Garnick, a Medical Oncologist at the BIDMC, the Gleason Score, a positive Digital Rectal Examination (DRE), and positive Lymph Nodes, are better indicators of disease progression, and should also be considered along with the PSA.

2.11 Weight Gain and smoking May make prostate cancer deadlier. Men who put on pounds after prostatectomy nearly double the odds of recurrence, one study finds.  (R231, R235)
Men treated for prostate cancer who smoke or put on excess pounds raise their odds of disease recurrence and of dying from the illness, two studies show. The findings were presented at the American Association for Cancer Research’s annual meeting in Washington, D.C. April, 2010. (R231)
A team led by Dr. Jing Ma, an associate professor of medicine at Brigham and Women’s Hospital in Boston, found that obesity and smoking may not be risk factors for developing prostate cancer, but they do increase the odds that a man who has the illness will die from it. Use R231 R235, R132C.
However, in Reference R132, Dr Matthew Smith, director of genitourinary medical oncology at Massachusetts General Hospital Cancer Center in Boston said, the relationship between PSA recurrence and death from prostate cancer is relatively weak. “The real question that matters is, OK, you’re diagnosed with the disease. Does your body mass index predict your risk of dying from cancer?
Being heavy and smoking “predispose men to a significantly high risk of cancer-specific and all-cause mortality,” Dr. Ma, from the Brigham and Women’s Hospital said. “Compared to lean non-smokers, obese smokers had the highest risk of prostate cancer mortality,” she said. Use R231 R235, R453

2.12 A database from the Health Professionals follow-Up Study of 51,529 male health professionals was documented in the June 2011 issue of JAMA, to determine the effect of smoking at the time of a CaP diagnosis. The results indicated an increased CaP-specific, overall and cardiovascular disease mortality and higher recurrence rates.  R467

2.13 A team led by Corinne E. Joshu, in the department of epidemiology at Johns Hopkins Bloomberg School of Public Health, found that men who gained weight after having their prostate removed were almost twice as likely to see their cancer return as were men who maintained their weight. Use (R235).  But another study indicated the effects vary by race (R235).
Men who put on a significant number of pounds after their 20s face a higher risk of prostate cancer than those who remain close to their youthful weight — but the effects vary by race, the study indicated.
Researchers found that among nearly 84,000 middle-aged and older U.S. men followed for about a decade, white and African-American men who had gained weight since the age of 21 had a higher risk of developing prostate cancer.
Compared with white men, who gained fewer than 10 pounds, those who gained more had twice the risk of being diagnosed with advanced or aggressive prostate cancer.
Among black men, the risks began increasing after a 25-pound weight gain — though the link was seen only with early-stage and less-aggressive prostate tumours, and not advanced cancer.
In contrast, men of Japanese descent actually saw their prostate cancer decline with weight gain.

2.14 Lymphatic invasion has been associated with biochemical recurrence, and many patients with postoperative elevation of prostate-specific antigen (PSA) develop distant metastases within several years.  This is a URO article.(See Stan’s Comment pertaining to Reference R737)
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2.15 Procedure to Slow a Recurrence
Studies show that the sooner secondary, salvage treatment starts, the risk of another recurrence is decreased by 35% R1006   However in 2001 the University of Texas said that salvage radiation does not help extend life. See Comment in paragraph 3.4.

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3.0 COMMENTS
This section alerts the reader to be vigilant about incorrect treatments and other items to be considered to hopefully help you avoid a recurrence. It also includes information to discuss with your doctor about when to be treated if a PSA increase after treatment. Please note that every increase in a PSA requires treatment
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3.1 Incorrect Treatment
An Incorrect Treatment may be that you were treated for a cancer that was more advanced than the doctor thought; consequently the entire cancer was not removed. For example, if the cancer has spread past the prostate, and migrated into the area immediately around the prostate (the Fossa), the surgical removal of the prostate will not have removed all the cancer, and a recurrence is almost guaranteed. In this case external beam radiation might have been a better choice, as external beam radiation, treats both the prostate and the surrounding area. This is why a newly diagnosed man should see all three PC specialists, to obtain a more thorough analysis, before a treatment choice. Note that consulting with all three PC specialists is no assurance that a recurrence will not occur, but it may decrease the chances.
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3.2 Other Considerations
If the  lymph nodes and/ or seminal vesicles, contain PC  there is a greater chance of recurrence An aggressive PC with a Gleason Grade of 8,9, or 10, and /or a  high PSA >20, usually is also a precursor for a recurrence, and may need more aggressive treatment from the start. I believe, these cancers should be treated by a Medical Oncologist who specializes in Genitourinary Cancers…
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3.3 Recurrence does NOT mean death
A recurrence, and even a second recurrence, does not mean you will die. Instead, it usually means further treatment will be recommended. Most men die WITH, not FROM, prostate cancer.
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3.4 Salvage Treatment
Salvage Treatment. I believe the sooner secondary, salvage treatment starts, as mentioned in paragraph 2.12, the less chance the cancer has to spread /advance. This was my situation, 1993 when I had an aggressive PC that had not yet advanced. It was estimated that I had two years to live. That was in 1993 !

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References
R132- CanWest News Service, Published: Monday, November 12, 2007
R132C- the British Journal of Urology International (Volume 100, page 315).  2007
R203-Journal of the American Medical Association. 2007;298:1533-1538
R231
Presentation, American Association for Cancer Research annual meeting, April 17-21, 2010, Washington, D.C.
R235 : Cancer Epidemiology, Biomarkers and Prevention, September 2009
R356-PubMed Abstract PMID: 21427585     Department of Urology, Vita-Salute University San Raffaele, Milan, Italy  2011
R453 Reference: JAMA. 2011 Jun 22;305(24):2548-55.   PubMed Abstract  PMID: 21693743 Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
R467 JAMA. 2011 Jun 22;305(24):2548-55     PMID Abstract : 21693743
R711– December 1, 2009 issue of the International Journal of Radiation Oncology*Biology*Physics.
R732: Mayo Prostate Cancer Test Gives Hope When Tumors Return 3/13/2013. (RegGale at rgale5@bloomberg.net)
Ref R737: Renal & Urology News    March 18, 2013
Ref 1001- Prostate Cancer Communication –March 2006, Page 1
Ref 1002- Prostate Cancer Communication-March 2006-Page 12   was Used
Ref 1003- US TOO International Hot Sheet,1/2003
R1004-University of Texas Health Science Center, Nov. 2006
R1005-Lecture at LMA- PC Support Group Dr P. Church 10/06
R1006-Lahey Clinic Study presented at American Urological Association, 2001 (A-149)
Dr John Libertino, Lahey Clinic, as reported 6/4/2001 in Boston Herald R1007-J.Urol .2010 Aug 17. E Pub ahead of print.  PubMed abstract PMID: 20723925
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April 21, 2013  Rev-B