Archive for May, 2019

Prostate Cancer Screening Biomarkers: What You Need To Know

May 25, 2019

Andrew Siegel MD  5/25/19

Before we get to the main course, let’s begin with a little appetizer—some trivia about urology, the occupation of yours truly.  There are not many of us around; there are currently 12,700 practicing urologists in the USA, 1 for every 25,000 Americans.  90% of  are male and 10% are female. 57% of urologists are in private practice and the remainder are employed by hospitals or academic medical centers. 40% of urologists have a primary subspecialty, oncology (cancer) being the most common.

Although I have subspecialty training and board certification in female pelvic medicine and reconstructive surgery, I enjoy general urology, treating both male and female adults with a variety of conditions (voiding and sexual dysfunction, incontinence, pelvic organ relaxation, urological cancers, infections, kidney stones, bleeding, vasectomy, etc.), the balance between office and surgical practice and—most importantly– the fact that as urologists, we can help most patients improve their quality and quantity of life.  

 

Bi·o·mark·er

/ˈbīōˌmärkər/
noun
plural noun: biomarkers
  1. a measurable substance in an organism whose presence is indicative of some phenomenon such as disease, infection, or environmental exposure.

Prostate specific antigen (PSA) was the first prostate cancer biomarker, singularly responsible for revolutionizing the diagnosis and follow-up of prostate cancer. There are several new biomarkers that can help with the decision of whether or not to biopsy the prostate as well as to inform and support prostate cancer management decisions (active surveillance vs. active treatment, the specific means of treatment for early and localized cancer, and when to pursue androgen deprivation therapy).

Prostate health index (PHI): This is a compilation of several different PSA sub-types, including pro-PSA, free PSA and total PSA, into a single score. It can help discriminate between higher and lower grade disease. PHI score coupled with other factors including age, prostate volume, digital rectal examination (DRE) {abnormal DRE vs. normal DRE} and biopsy history (prior prostate biopsy vs. no prior prostate biopsy) are used to help determine the need for biopsy in a patient with suspected prostate cancer.

Prostate cancer antigen (PCA3) urine test: PCA3 is a specific type of RNA (ribonucleic acid) that is released in high levels by prostate cancer cells. Its expression is 60-100 times greater in prostate cancer cells than benign prostate cells, which makes this test much more specific for prostate cancer than PSA. The first ounce of urine voided immediately after prostate massage (a vigorous DRE with the intent of milking the prostate) is rich in prostatic fluid and cells and is collected and tested for the quantity of PCA3 genetic material present. Urinary levels of PCA3 are not affected by prostate enlargement or inflammation, as opposed to PSA levels. PCA3 > 25 is suspicious for prostate cancer.

4Kscore test:  4Kscore test measures blood levels of four different prostate-derived proteins: total PSA, free PSA, intact PSA and human kallikrein 2. Levels of these biomarkers are combined with the patient’s age, DRE, and history of prior biopsy. These factors are processed using an algorithm to calculate the risk of finding an aggressive prostate cancer (Gleason score 7 or higher) if a prostate biopsy were to be performed. The test can increase the accuracy of prostate cancer diagnosis, particularly in its most aggressive forms.  It cannot be used if a patient has had a DRE in the previous 4 days, nor can it be used if one has taken finasteride (Proscar) or dutasteride (Avodart) within the previous six months. Additionally, it cannot be used in patients who have undergone any procedure to treat symptomatic prostate enlargement or any invasive urologic procedure in the prior 6 months.

Apifiny test:  This test measures the immune response to prostate cancer, detecting autoantibody proteins in the blood that are produced against prostate cancer cells. It is a risk assessment tool that does not rely on PSA. A score of 1-100 is given: the higher the score, the greater the chance for the presence of prostate cancer.

Biomarker to confirm a negative (benign) biopsy:

ConfirmMDx:  Since a biopsy of the prostate samples only a small volume of the total prostate, it is possible to have benign biopsy results when in fact an underlying cancer was missed.  This particular assay is done on prostate tissue derived from a negative biopsy to help determine its accuracy. It quantitates the chemical status of certain genes to detect abnormal changes associated with the presence of prostate cancer. ConfirmMDx detects a “halo” associated with the presence of cancer at the DNA level, which may be detected in prostate cancer tissue despite a normal microscopic appearance. This test helps identify low risk men who may forego a repeat biopsy and high risk men who would benefit from a repeat biopsy.

Wishing you the best of health,

2014-04-23 20:16:29

A new blog is posted weekly. To receive a free subscription with delivery to your email inbox visit the following link and click on “email subscription”:  www.HealthDoc13.WordPress.com

Dr. Andrew Siegel is a physician and urological surgeon who is board-certified in urology as well as in female pelvic medicine and reconstructive surgery.  He is an Assistant Clinical Professor of Surgery at the Rutgers-New Jersey Medical School and is a Castle Connolly Top Doctor New York Metro Area, Inside Jersey Top Doctor and Inside Jersey Top Doctor for Women’s Health. His mission is to “bridge the gap” between the public and the medical community. He is a urologist at New Jersey Urology, the largest urology practice in the United States.

The content of this entry is excerpted from his new book, PROSTATE CANCER 20/20: A Practical Guide to Understanding Management Options for Patients and Their Families

4 small

Video trailer for Prostate Cancer 20/20

Preview of Prostate Cancer 20/20

Andrew Siegel MD Amazon author page

Prostate Cancer 20/20 on Apple iBooks

Dr. Siegel’s other books:

FINDING YOUR OWN FOUNTAIN OF YOUTH: The Essential Guide to Maximizing Health, Wellness, Fitness and Longevity

PROMISCUOUS EATING— Understanding and Ending Our Self-Destructive Relationship with Food

MALE PELVIC FITNESS: Optimizing Sexual and Urinary Health

THE KEGEL FIX: Recharging Female Pelvic, Sexual, and Urinary Health

 

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Prostate MRI: What You Should Know

May 18, 2019

Andrew Siegel MD  5/18/2019

MRI (magnetic resonance imaging) is a high-resolution test that is an important tool for prostate cancer diagnosis, targeting of biopsies, clinical staging, surgical planning, follow-up of prostate cancer patients managed with active surveillance and in the evaluation of recurrent prostate cancer following treatment. A shout-out to Dr. Robert Waxman, who provided the MRI images seen below. 

MRI uses a powerful magnet to enable viewing of the prostate gland and surrounding tissues in multiple planes of view with the advantage of not requiring radiation. The planes are axial (cross section), sagittal (the plane that divides the body into left and right) and coronal (a plane dividing the body into dorsal and ventral parts). The axial images are by far the most important images of the study. MRI identifies areas suspicious for cancer and enables “targeted” biopsies as opposed tosystematic” biopsies. Although useful in the diagnostic evaluation of any man who has a suspicion of prostate cancer, it is particularly beneficial in men who have had previous benign prostate biopsies who have persistent PSA elevations or accelerations.

MRI is a valuable part of the diagnostic armamentarium, increasing the detection rate of clinically significant (Gleason score 7 or higher) prostate cancers, while reducing the detection rate of clinically insignificant (Gleason score 6) cancers. MRI provides anatomical details about the neuro-vascular (nerve and blood vessel) bundles, urinary bladder, seminal vesicles, pelvic lymph nodes, bowel and pelvic bones and beneficial staging information on tumor extension beyond the prostate capsule, pelvic lymph node enlargement and seminal vesicle involvement.

Prostate MRI is performed at specialty imaging centers.  Preparation involves a Fleet enema to clear gas from the rectum that can generate artifacts on the MRI images making interpretation suboptimal.  A coil placed in the rectum (endo-rectal coil) is no longer necessary as it was in prior versions of MRI. The study is done before and after the injection of about 20 cc of intravenous contrast to optimize the results.

Note: MRI cannot be performed under the following circumstances: pacemaker, recent coronary artery stent placement, ferromagnetic brain aneurysm clips and the presence of metal near the spinal cord, e.g., bullet fragments.

Refinements in MRI involve diffusion and perfusion studies. Diffusion is the movement of water into tissues; because prostate cancer cells are more tightly packed than normal cells, diffusion is often restricted with prostate cancers. Perfusion is the circulation of blood to tissues; because prostate cancers are hyper-vascular (increased blood supply), with the injection of the intravenous contrast there is increased perfusion with prostate cancers.

The value of prostate MRI is highly operator-dependent and requires both a quality study and interpretation by a skilled and experienced radiologist. Sophisticated software performs image analysis, assisting radiologists in interpreting and scoring MRI results. A validated scoring system known as PI-RADS (Prostate Imaging Reporting and Data System) is used. This scoring system helps urologists make decisions about whether to biopsy the prostate and, if so, how to optimize the biopsy.

PI-RADS      

I     most probably benign (clinically significant cancer highly unlikely)

II    probably benign (clinically significant cancer unlikely)

III   indeterminate (clinically significant cancer equivocal) — 20% chance

IV   probably cancer (clinically significant cancer likely) — 50% chance

V   most probably cancer (clinically significant cancer highly likely) —75% chance

Of note, the IV and V groups are the same, differentiated only by the size of the suspicious region. In the IV group the abnormality is < 1.5 cm; in the V group the abnormality is > than 1.5 cm in diameter.

Now let’s play radiologist.  Can you identify the suspicious regions in the following two images?  There is a magnified view of the abnormal sites at the end of this entry.  Radiology clue: when you view images, always be on the look out for asymmetries between the left and right.

MRI1

Patient 1 with a PIRADS-5 lesion

 

MRI2

Patient 2 with a PIRADS-5 lesion with mass effect on the rectum and likely extra-capsular extension

MRI is by no means a perfect test, as clinically significant cancers (particularly small ones) are not always apparent on MRI, and PIRADS-4 and PIRADS-5 lesions when biopsied are not always found to contain clinically significant cancers. An additional concern is its expense.  Some urologists believe in obtaining a prostate MRI on all patients prior to performing a prostate biopsy, whereas others reserve MRI for patients with a previous negative biopsy in the face of a rising PSA. In the former setting, a biopsy remains the only definitive means of assessment regardless of the PIRADS score, one of the key utilities of the MRI being to help precisely target the biopsy.  However, in the latter setting, when the MRI reading is PIRADS-1 or PIRADS-2, a repeat biopsy can often be avoided.

Fact: PSA, DRE and MRI are all useful and informative tests, but the prostate biopsy (tissue sampling) is the only way to know for sure if one has prostate cancer.  In other words, whereas PSA, DRE and MRI are “suggestive,” the biopsy is “definitive.” “The buck stops here” applies to the biopsy.

unnamed

Magnified view of lesion of figure 1

 

unnamed (12

Magnified view of lesion of figure 2

Final note: Most insurance companies will readily cover the cost of a MRI study prior to doing a prostate biopsy.  The exception is CIGNA, which apparently cares more about its bottom line than the welfare of its insured patients.  I am constantly fighting with CIGNA-employed physicians in “peer-to-peer” conversations in an effort to get the company to pay for a pre-biopsy MRI.  My last such conversation was two days ago and sadly, I have never prevailed.

Wishing you the best of health,

2014-04-23 20:16:29

A new blog is posted weekly. To receive a free subscription with delivery to your email inbox visit the following link and click on “email subscription”:  www.HealthDoc13.WordPress.com

Dr. Andrew Siegel is a physician and urological surgeon who is board-certified in urology as well as in female pelvic medicine and reconstructive surgery.  He is an Assistant Clinical Professor of Surgery at the Rutgers-New Jersey Medical School and is a Castle Connolly Top Doctor New York Metro Area, Inside Jersey Top Doctor and Inside Jersey Top Doctor for Women’s Health. His mission is to “bridge the gap” between the public and the medical community. He is a urologist at New Jersey Urology, the largest urology practice in the United States.

The content of this entry is excerpted from his new book, PROSTATE CANCER 20/20: A Practical Guide to Understanding Management Options for Patients and Their Families

4 small

Video trailer for Prostate Cancer 20/20

Preview of Prostate Cancer 20/20

Andrew Siegel MD Amazon author page

Prostate Cancer 20/20 on Apple iBooks

Dr. Siegel’s other books:

FINDING YOUR OWN FOUNTAIN OF YOUTH: The Essential Guide to Maximizing Health, Wellness, Fitness and Longevity

PROMISCUOUS EATING— Understanding and Ending Our Self-Destructive Relationship with Food

MALE PELVIC FITNESS: Optimizing Sexual and Urinary Health

THE KEGEL FIX: Recharging Female Pelvic, Sexual, and Urinary Health

 

Laser Vaginal Therapy: Hope or Hype?

May 11, 2019

Andrew Siegel MD 5/11/2019

HAPPY MOTHER’S DAY!

For better or for worse, we are living in the era of “vaginal rejuvenation.”  Procedures referred to as “designer vaginoplasty,” “re-virgination,” “reduction labioplasty,” “G-spot amplification,” “platelet-rich plasma (PRP) injections,” “vaginal bleaching,” etc., have come into vogue as expensive plastic procedures advertised by some entrepreneurial physicians for cash-paying patients. Within the domain of “vaginal rejuvenation,” the last few years have also witnessed an explosion in the availability of office-based vaginal laser therapies for a variety of conditions, including vaginal dryness and other symptoms of menopause, vaginal (laxity) looseness, and stress urinary incontinence.

Vagina collage public domain

Vaginal Collage (public domain)

LASER = light amplification and stimulated emission of radiation

The theorized mechanism of action of laser therapy is collagen and elastin fiber remodeling, growth of new collagen, blood vessel ingrowth and growth factor infiltration.  The goal is the restoration of vaginal elasticity, suppleness and moistness that often decline after menopause with the cessation of estrogen production, a hormone that contributes vitally to female genital health.

In the USA, these procedures are costly and not covered by insurance. They are most commonly performed by gynecologists, but any MD with a license or their nurse practitioners or physician assistants can legally perform these laser procedures.  Lasers are expensive to purchase or lease and private physicians charge an “arm and a leg” to treat the vagina, since these procedures are outside the domain of health insurance.

The problem is the lack of scientific evidence regarding effectiveness of laser procedures as well as the possibility of serious adverse effects (including itching, burning, redness, scarring, swelling, pain during intercourse and chronic pain). In July of 2018, the FDA issued a warning against the use of energy-based devices– including lasers and radio-frequency devices– for vaginal rejuvenation and vaginal cosmetic procedures.

The bottom line is that although there is some evidence of effectiveness based upon observational studies, there exists a strong need for long-term, large, randomized and placebo-controlled clinical trials to evaluate the safety and effectiveness of these vaginal laser procedures before they can be recommended.

As a urologist, I often use lasers for fragmenting stones in the urinary tract (bladder, ureters and kidneys) and for creating a channel through an obstructed prostate gland. These are legitimate and bonafide uses of lasers in medicine. My urology group does not utilize vaginal laser therapy (although its use was considered, but voted down after considerable research).  I do have some patients who have had vaginal laser procedures outside of my practice to manage symptoms of menopause, vaginal laxity and stress urinary incontinence. Anecdotally, I have one patient who speaks very highly of the fractional laser therapy she received for post-menopausal dryness, which seemed to improve her situation.

With respect to vaginal laxity and stress urinary incontinence, my feeling is that as fabulous and high-tech as lasers are, in these two cases lasers are a solution in search of a problem and are ineffective options for the management of these problems. If a woman truly has vaginal laxity–often accompanied by pelvic organ prolapse–or significant stress urinary incontinence she will often benefit from surgical therapy if unresponsive to conservative treatments.  Furthermore, my advice is to stay away from vaginal bleaching, G-spot amplification, PRP injections, and re-virgination insanity.  Labiaplasty is a reasonable consideration if a woman has outsized labia that get in the way of life’s activities, but otherwise my advice is to maintain a healthy lifestyle and pursue pelvic floor exercises as a means of vaginal fitness.

Bottom Line:  Laser Vaginal Therapy: Mostly hype with a bit of hope.  As always, caveat emptor (buyer beware)!

Wishing you the best of health,

2014-04-23 20:16:29

A new blog is posted weekly. To receive a free subscription with delivery to your email inbox visit the following link and click on “email subscription”:  www.HealthDoc13.WordPress.com

Dr. Andrew Siegel is a physician and urological surgeon who is board-certified in urology as well as in female pelvic medicine and reconstructive surgery.  He is an Assistant Clinical Professor of Surgery at the Rutgers-New Jersey Medical School and is a Castle Connolly Top Doctor New York Metro Area, Inside Jersey Top Doctor and Inside Jersey Top Doctor for Women’s Health. His mission is to “bridge the gap” between the public and the medical community. He is a urologist at New Jersey Urology, the largest urology practice in the United States.

Dr. Siegel’s newest book, PROSTATE CANCER 20/20: A Practical Guide to Understanding Management Options for Patients and Their Families

Video trailer for Prostate Cancer 20/20

Preview of Prostate Cancer 20/20

Andrew Siegel MD Amazon author page

Prostate Cancer 20/20 on Apple iBooks

Dr. Siegel’s other books:

FINDING YOUR OWN FOUNTAIN OF YOUTH: The Essential Guide to Maximizing Health, Wellness, Fitness and Longevity

PROMISCUOUS EATING: Understanding and Ending Our Self-Destructive Relationship with Food

MALE PELVIC FITNESS: Optimizing Sexual and Urinary Health

THE KEGEL FIX: Recharging Female Pelvic, Sexual, and Urinary Health

one-sheet-poster

 

Refinements and Nuances of PSA Testing: What You Need to Know

May 4, 2019

Andrew Siegel MD  5/4/19

mannequin pis

Above photo is of the famous Mannekin Pis statue in Brussels

Last week’s entry discussed the basics of PSA—”PSA 101” if you will. Today is the “300-level  course” that reviews refinements in PSA testing that make the test more valuable, meaningful and predictive.  

What are some of the refinements and nuances in PSA (Prostate Specific Antigen) testing?

PSA Velocity:  Comparing one’s PSA values year-to-year is most informative. Generally, PSA will increase by only a small increment, reflecting benign prostate growth associated with the aging process. If PSA accelerates faster than anticipated—a condition known as accelerated PSA velocity—further evaluation is indicated.  The bottom line is that an isolated PSA (out of context) is much less meaningful than a series of one’s PSAs over time.

Please note: Many labs use a PSA of 4.0 as a cutoff for abnormal, so it is possible that one can be falsely lulled into the impression that their PSA is normal.  For example, if one’s PSA is 1.0 and a year later it is 3.0, it is still considered a “normal” PSA (because it is less than 4.0) even though it has tripled (highly suspicious for a problem) and mandates further investigation.  So, it is worthwhile knowing your actual PSA level, similar to being aware of your cholesterol level.

PSA Density:  The larger the prostate, the more PSA that is manufactured.  PSA density (PSA divided by prostate volume) is the PSA level corrected to prostate size. The prostate volume can be determined by imaging studies including ultrasound or MRI.  PSA elevations are less worrisome under the circumstance of an enlarged prostate.

A PSA density > 0.15 is concerning for prostate cancer.

Free PSA:  PSA circulates in the blood in two forms: a “free” form in which the PSA is unbound, and a “complex” PSA in which the PSA is bound to a protein. The free PSA/total PSA ratio can offer a predictive value (similar to how HDL cholesterol/total cholesterol can be helpful in a person with an elevated cholesterol level). The higher the free to total PSA ratio, the greater the chance that benign enlargement of the prostate is the underlying source of the PSA elevation.

In men with a PSA ranging from 4-10, the probability of cancer is:

9-16% if the free/total PSA ratio is greater than 25%

18-30% if the ratio is 19-25%

27-41% if the ratio is 11-18% 

49-65% if the ratio is less than 10%

4Kscore test: The 4Kscore Test is a refinement that measures the blood content of four different prostate-derived proteins: total PSA, free PSA, intact PSA and human kallikrein 2. Levels of these biomarkers are combined with a patient’s age, DRE (digital rectal examination) status (abnormal DRE vs. normal DRE), and history of prior biopsy status (prior prostate biopsy vs. no prior prostate biopsy). These factors are processed using an algorithm to calculate the risk of finding a Gleason score 7 or higher (aggressive) prostate cancer if a prostate biopsy were to be performed. The test can increase the accuracy of prostate cancer diagnosis, particularly in its most aggressive forms. (It cannot be used if a patient has received a DRE in the previous 4 days, nor can it be used if one has been on Avodart (dutasteride) or Proscar (finasteride) within the previous six months. Additionally, it cannot be used in patients that have within the previous six months undergone any procedure to treat symptomatic prostate enlargement or any invasive urologic procedure that may be associated with a PSA elevation.)

How is PSA used in men diagnosed with and treated for prostate cancer?

PSA is unquestionably the best marker to gauge prostate cancer status in the follow-up of men who have been treated for prostate cancer by any means or in those men who are on active surveillance.

After surgical removal of the prostate gland for cancer the PSA should be undetectable and after radiation therapy the PSA should decline substantially to a reading of usually less than 1.0. Rising PSA levels after treatment may be the first sign of cancer recurrence.  Such a “biochemical” relapse typically precedes a “clinical” relapse by months or years.  If a man on active surveillance has consecutive substantial elevations in PSA level, it signals the possibility of more aggressive disease that may require active intervention.

Is PSA the definitive test for prostate cancer?

No! PSA is the definitive test for monitoring prostate cancer and a good, but imperfect screening test since the PSA can be elevated in the absence of prostate cancer and low in the presence of prostate cancer.

An elevated or accelerated PSA, abnormal digital rectal exam and suspicious MRI are all helpful tests, but remember that the definitive and conclusive test for prostate cancer is the ultrasound-guided prostate biopsy.

“The buck stops here” with prostate biopsy, the conclusive test for prostate cancer.

Wishing you the best of health,

2014-04-23 20:16:29

A new blog is posted weekly. To receive a free subscription with delivery to your email inbox visit the following link and click on “email subscription”:  www.HealthDoc13.WordPress.com

Dr. Andrew Siegel is a physician and urological surgeon who is board-certified in urology as well as in female pelvic medicine and reconstructive surgery.  He is an Assistant Clinical Professor of Surgery at the Rutgers-New Jersey Medical School and is a Castle Connolly Top Doctor New York Metro Area, Inside Jersey Top Doctor and Inside Jersey Top Doctor for Women’s Health. His mission is to “bridge the gap” between the public and the medical community. He is a urologist at New Jersey Urology, the largest urology practice in the United States.

The content of this entry is excerpted from his new book, PROSTATE CANCER 20/20: A Practical Guide to Understanding Management Options for Patients and Their Families

4 small

Video trailer for Prostate Cancer 20/20

Preview of Prostate Cancer 20/20

Andrew Siegel MD Amazon author page

Prostate Cancer 20/20 on Apple iBooks

Dr. Siegel’s other books:

FINDING YOUR OWN FOUNTAIN OF YOUTH: The Essential Guide to Maximizing Health, Wellness, Fitness and Longevity

PROMISCUOUS EATING— Understanding and Ending Our Self-Destructive Relationship with Food

MALE PELVIC FITNESS: Optimizing Sexual and Urinary Health

THE KEGEL FIX: Recharging Female Pelvic, Sexual, and Urinary Health