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Abstract

Radical prostatectomy in men aged ≥70 years: effect of age on upgrading, upstaging, and the accuracy of a preoperative nomogram

British Journal of Urology International

Volume 101 Issue 5 Page 541-546, March 2008

• Lee Richstone, *The Smith Institute for Urology, The North Shore-LIJ Health System, The Albert Einstein College of Medicine
• Fernando J. Bianco**Department of Urology, George Washington University Hospital, ,
• Hiral H. Shah,
• Michael W. Kattan††Department of Quantitative Health Sciences, Cleveland Clinic, ,
• James A. Eastham‡‡Department of Urology, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, and ,
• Peter T. Scardino‡‡Department of Urology, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, and and
• Douglas S. Scherr§§Department of Urology, New York Presbyterian-Weill Cornell Medical Center, New York, NY, USA

• The Smith Institute for Urology, The North Shore-LIJ Health System, *Department of Urology, George Washington University Hospital, †Department of Quantitative Health Sciences, Cleveland Clinic, ‡Department of Urology, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, and §Department of Urology, New York Presbyterian-Weill Cornell Medical Center, New York, NY, USA

: RRP , radical retropubic prostatectomy ; OCD , organ-confined disease ; MSKCC , Memorial Sloan-Kettering Cancer Center ; CSS , cancer-specific survival ; OS , overall survival ; EPE , extraprostatic extension ; SVI , seminal vesicle invasion ; PFP , progression-free probability.

Study Type – Therapy (outcomes research)
Level of Evidence  2b

OBJECTIVES

To determine the effect of age on clinicopathological features, the accuracy of the preoperative nomogram, and survival after radical retropubic prostatectomy (RRP), as there are limited data on elderly men undergoing RRP.

PATIENTS AND METHODS

A database of 258 men aged ≥70 years and 3777 aged <70 years who had RRP was reviewed to compare the clinicopathological features and survival between the age groups. The effect of age on the frequency of upgrading from biopsy Gleason sum 2–6 to pathology Gleason sum ≥7, and upstaging from clinical T1–T2 to pathological stage T3–T4 was also evaluated.

RESULTS

Men aged ≥70 years had cancers of higher clinical stage (P = 0.001), pathology Gleason sums (P = 0.01) and a lower frequency of organ-confined disease than men aged <70 years (58.1% and 69.9%, respectively, P = 0.001). There was upgrading in 76/169 (45.0%) men aged ≥70 years and in 936/2656 (35.2%) of men aged <70 years (P = 0.01). However, age was not associated with upgrading on a multivariate analysis. Upstaging was more frequent in older than in younger men (40.2% and 29.3%, respectively, P = 0.001). Age ≥70 years was associated with upstaging on multivariate logistic regression but did not affect the accuracy of the Partin tables (P = 0.14) or Kattan nomograms (P = 0.53). There was no difference in cancer-specific survival (96% at 10 years, P = 0.33) or biochemical progression-free probability between the age groups (74% and 75% at 10 years, respectively, P = 0.13).

CONCLUSIONS

Patients aged ≥70 years are more likely to be upstaged after RRP, but this does not affect cancer control. In addition, nomograms maintain their accuracy and remain valid tools in this rapidly growing patient population.

Below is a story that Reuters News Service ran earlier this week on Dr. Richstone’s publication regarding radical prostatectomy for treating older men with prostate cancer.

http://www.clpmag.com/reuters_article.asp?id=20080430clin019%2Ehtml Radical prostatectomy a good option for some older men with prostate cancer

 The North Shore-LIJ Health System, The Arthur Smith Institute for Urology>Lee Richstone, M.D.,  Director of Laparoscopy and Robotic Surgery

Most men are likely to have health issues related to the prostate in the course of their lifetimes. With September being National Prostate Cancer Awareness Month, we have the opportunity to discuss this critical issue related to Men’s Health. Just like our gynecology counterparts who serve as advocates for Women’s Health, urologists aim to champion Men’s Health by raising awareness and helping to educate men about their bodies. With that in mind, here are some essential facts regarding prostate cancer that all men, and their loved ones, need to know.

What is the prostate?
The prostate is a gland involved in male reproduction. Specifically, it produces some of the ejaculate fluid that is released when a man reaches orgasm. Normal prostate fluid contains Prostate Specific Antigen (“PSA”), an enzyme that is necessary for the semen to result in a pregnancy. PSA is also important, as will be discussed in more detail later, because abnormal levels of PSA in the blood can be a clue that something is wrong with the prostate, including cancer.

Where is the prostate?
The prostate is roughly the size of a walnut; however, there is great variation in size, especially as men get older. The prostate lies just below the bladder and right in front of the rectum. The

urethra (the tube that drains urine from the bladder and out the penis) runs right through the middle of the prostate much like the core through an apple. As such, enlargement of the prostate can squeeze the urethra and make urination difficult. This can lead to symptoms such as poor urine flow and urinary frequency, both during the day and night. Such symptoms are most commonly caused by non-cancerous conditions, such as benign prostatic hypertrophy (BPH), inflammation, or infection. Although most prostate cancers are asymptomatic, prostate cancer can occasionally cause urinary symptoms or, if it spreads to the bone, pain.Examining the Prostate
Because the prostate sits right in front of the rectum, a physician can feel the surface of the prostate by placing a finger in the rectum (a “digital rectal exam”, or DRE). This can allow for the detection of any “lumps” or “bumps” which might represent prostate cancer. Another important anatomical point is that the nerves that allow a man to achieve an erection (the “neurovascular bundles” or “cavernous nerves”) lie on either side of the prostate, and are vulnerable to injury during radiation or surgery.

What is prostate cancer?
Every part of the body is made up of fundamental building blocks: cells. For example, the liver is made up of millions of liver cells and the prostate is made of innumerable prostate cells. Each individual cell is alive and has a variety of functions. All of this activity is tightly regulated, following the “instructions” encoded in our DNA.

Cancer is what happens when cells begin to grow, multiply, and act on their own in an unregulated fashion. The result is that a “mass” or “tumor” of such cells develops. These cells are abnormal in other ways, too. Instead of staying in their normal location, they can acquire the ability to travel throughout the body and start growing in other locations, causing problems. Prostate cancer develops when prostate cells start acting in these abnormal ways.

Who gets prostate cancer?
Prostate cancer is the most commonly diagnosed cancer, and third leading cause of cancer related death, among American men. In 2006, approximately 234,000 men will be diagnosed with prostate cancer, and about 27,000 will die from prostate cancer. Put another way, the average man has a 17% chance of getting prostate cancer in the course of his lifetime, and a 3% chance of dying from this disease. Men with a family history, black men, and overweight individuals, or those on a high fat diet are at increased risk of developing prostate cancer.

Who should be screened for prostate cancer, and when?
The American Urologic Association (AUA) recommends that all men beginning at 50 years old should be screened for prostate cancer. Screening involves both a blood test that detects higher than normal Prostate Specific Antigen (PSA) level and a digital rectal exam (DRE) that allows your physician to feel the prostate gland. Because either method of screening (PSA or DRE) can miss some cancers, both tests should be performed. In addition, men at higher risk, such as African American men and men with first-degree relatives who had prostate cancer, should be screened from age 40.

If my PSA or DRE is abnormal, does that mean I have prostate cancer?
Most studies demonstrate that approximately 3 out of 4 patients (75%) with abnormal screening tests will not have prostate cancer detected on prostate biopsy. Part of the reason for this is that other conditions (e.g. infection, urinary retention, or other causes) can cause elevations in blood PSA levels.Although PSA screening and digital rectal examinations are very sensitive tests for diagnosing people with prostate cancer (i.e. most people with cancer will be detected), they are not perfectly specific. This means that many people without cancer can also have an elevated PSA or abnormal DRE.

In order to make a conclusive diagnosis, a man with an elevated PSA or abnormal DRE needs to undergo a prostate biopsy, which involves microscopic examination of small pieces of prostate tissue to look for the presence of prostate cancer.

Cancer Grade and Stage
If a diagnosis of prostate cancer is made, several factors help doctors determine how “aggressive” the cancer is. Put another way, we try to determine the risk that the cancer is going to affect the patient’s health and survival. Making such an assessment allows the patient and physician to make informed decisions about the best treatment for each individual, based on cancer grade and stage.

Cancer grade is determined by the way the cancer cells look under the microscope. Specifically, the cancer can be given a score between 2-10, called the Gleason score. Cancers with low Gleason scores (i.e. closer to 2) are less “dangerous” than those with high scores (i.e. closer to 10). This is one important way that physicians can predict the behavior of a cancer, and help recommend appropriate treatment.

Cancer stage, in contrast, is a way to describe the extent of the cancer at the time of diagnosis. For example, if a cancer cannot be felt on rectal exam and was only detected via an abnormal PSA blood test, it would be deemed stage T1c. A cancer that could be felt on rectal exam but did not appear to spread outside of the prostate would be stage T2. Cancers that have already spread outside of the prostate are called stage T3 or T4, depending on the extent of spread. Like cancer grade, cancer staging helps to predict the behavior of the cancer and helps to guide treatment. In certain cases, a CT scan and/or a bone scan may be necessary to determine if it has spread outside of the prostate.

Options for Treatment
Perhaps the most important issue regarding prostate cancer is choosing the right treatment for each individual patient. Prostate cancer treatment can generally be divided into several options: active surveillance, radiation, surgery, ablative therapy (freezing or cooking), and hormone deprivation. Active surveillance, also referred to as “watchful waiting”, involves “watching” the cancer by checking PSA levels in the blood, feeling the prostate (by performing a DRE), and repeating the prostate biopsy. Most urologists treating patients in this manner check the PSA and perform the DRE every 6 months, and repeat the biopsy every 12 months. If any of these repeat tests (PSA, DRE, biopsy) suggest that the cancer is more “risky” than originally thought, “definitive” treatment with surgery or radiation is typically recommended.

Although most prostate cancers are clinically significant (i.e. they will affect the patient’s health and lifespan), sometimes doctors detect cancers that are small, low grade, and are unlikely to do any harm. With careful grading and staging of the cancer, certain patients can be “watched” successfully. More aggressive treatment can be initiated if the features of the cancer appear to “change”. In general, only patients with low risk (low grade and low stage) and low volume (small) cancers should be considered for active surveillance. It is critically important to have good, open communication with your urologist to explore all options to determine the right one for you.

Alternatively, many men choose radiation or surgical treatment for prostate cancer. Radiation can be administered via external beam radiation therapy (XRT), or brachytherapy (BT). The latter involves placing radioactive “seeds” within the prostate. New technology is available to minimize risk of radiating surrounding healthy tissue including the rectum, bladder and nerves responsible for errections. However, in order to treat the edges of the prostate, some surrounding tissue is affected. Brachytherapy may be as effective as XRT or surgery for men with low risk cancer, but caution should be taken when considering “seeds” for intermediate- and high-risk prostate cancers. Like all treatment options for prostate cancer, radiation can have significant side effects including, but not limited to, impotence, difficulty with urination, and rectal complaints.

Surgical treatment of prostate cancer involves completely removing the prostate, as well as the seminal vesicles. (The seminal vesicles produce some of the ejaculate fluid, and can be a site of prostate cancer spread). The traditional approach to removing the prostate is by “open” surgery (the radical retropubic prostatectomy, or “RRP”). This involves an incision in the skin, which starts from just under the umbilicus (“belly button”) and goes down to the pubic bone. The prostate, seminal vesicles, and lymph nodes are removed.

Over the past decade, urologists have developed laparoscopic radical prostatectomy (“LRP”) and robotic prostatectomy. Both the LRP and robotic prostatectomy employ small (1/4 inch) incisions. The robotic assisted prostatectomy is very similar to the LRP. Many believe that robotic technology offers better optics and instrumentation that translate to better outcomes, however, this has not been definitively proven. Although it is well documented that robotic and laparoscopic approaches cause less bleeding than open surgery, the additional benefits of the robotic/laparoscopic approach are still being elucidated. Like radiation treatment, surgery can cause side effects in some patients, including leakage of urine and problems with achieving erections.

Ablative therapies are being evaluated and involve freezing (cryoablation) or cooking (High Intensity Focused Ultrasound-HIFU). These are relatively new methods and used in very specific circumstances. Cryoablation, for example, may be very useful in patients who failed prior radiation. There is also work being done with these technologies to treat the tumor and spare some of the prostate. Early results are promising, but further long term results will be needed.

Choosing the right treatment for prostate cancer is a complex and highly personal decision, requiring in-depth discussion with your urologist. For more information about prostate cancer screening, prevention, and treatment options, the team of urologists at North Shore-LIJ is here to help.

The news is filled with stories regarding prostate cancer.  Which treatment is best? Can my “nerves” be spared?  Do I need treatment at all?

It really is remarkable that despite all we have learned about prostate cancer over the last several decades, the answers to many basic questions are not clear for each and every man with prostate cancer.  

Prostate cancer is an extremely complex disease.  Each man with prostate cancer needs to be thought of individually; no single treatment option is best for everyone.  In many cases, prostate cancer does not even need immediate treatment.  It can be “watched” with an annual biopsy and a PSA every 6 months.  This is called “active surveillance” and is offered at the Smith Institute for Urology for select patients.  In other cases, the prostate cancer poses a more serious risk, and treatment is critical.   When treatment is necessary, choosing the right treatment depends on the grade of cancer (Gleason score), the prostate specific antigen (PSA) blood test, the clinical stage (based on your examination, x-ray studies), and patient factors such as age, family history, and feelings about potential side effects. 

There are certain cases where I have strong feelings that the data supports a particular treatment option, be it surgery, radiation, or surveillance.  In other low risk cases, choosing from the various options (robotic prostatectomy, brachytherapy (”seeds”), external radiation, cryotherapy, HIFU….) can be a complex challenge.  You need a urologist who will take time to review the options with you and help educate you.  Reading books and using the internet can be of great value, but be careful not to believe everything you read.  

In my next blog entry, I will share with you a novel approach to prostate cancer that may make your decision making easier.  In order to help make better choices, we offer “3-dimensional pathologic mapping biopsies of the prostate”.  To our knowledge, the Smith Institute for Urology is the only site in the New York area performing such biopsies.  This approach may change your thoughts on prostate cancer entirely, and help you make the right choice.  Stay tuned…..my next blog will give you details about mapping biopsies and what is involved.  -Lee Richstone, MD

As part of our Smith Blog-Journal Club Update, we will keep you informed with the latest in urologic literature.  Below is a brief synopsis by Dr. Nadya Cinman, one of our exceptional residents, regarding a recent article written on “PSA velocity”. PSA velocity is the speed at which the PSA blood test rises over time. The key point is that evaluating PSA levels is no longer a simple task.  A “cutoff” of 4 is inadequate to detect many prostate cancers.  It is important to realize that it is not only the absolute value of your PSA, but the speed with which it changes over time. Make sure your urologist follows your PSA closely, and realize that PSA velocity may be an indication for biopsy.  Please BLOG with questions or thoughts!  -Lee Richstone, MD

Loeb et. Al.  Prostate specific antigen velocity in men with total prostate specific antigen less than 4ng/ml. J Urol Dec 2007 178; 2348-2353.

Purpose:  A PSA velocity of >0.75 ng/ml/year has been used to distinguish benign versus malignant disease of the prostate.  This PSA velocity has been determined mostly by men whose total PSA levels were between 4 – 10 mg/ml.  This article aims to identify a PSA velocity threshold upon which to initiate malignant workup for men whose total PSAs are less than 4 ng/ml.

Methods:  This study, initiated by Dr Catalona at Northwestern, was a community based prostate screening study of approximately 26,000 men over a ten year period.  PSA tests and DRE exams were performed at 6-12 months, and included men >50 years old, and expanded to include men >40 years old with positive family history of prostate cancer or African-American.  For PSA >4ng/ml initially and then >2.5ng/ml later in the study, or for suspicious DREs, prostate biopsies were performed.  Regression analysis of PSA values was determined.

Results: Of the 11,800 patients with a total PSA <4 ng/ml, approximately 500 were diagnosed with PCA, at a median of 68 months (0-148 months). T1c disease was found in 70% of the patients, and T2 in 30%. Approximately 90% of the men had Gleason 6 or less, and 10% with Gleason 7 -10.  Median PSA velocity was 0 – 5.2ng/ml/year.  PCA was diagnosed in 2% with PSA velocity less than 0.4 mg/ml/year, and 13% with PSA velocity greater than 0.4 ng/ml/year. In summary, the majority of patients with PCA with a total PSA < 4 ng/ml/year will have a PSA velovity < 0.75 ng/ml/year and in recognition of men with lower total PSAs, a PSA velocity threshold of 0.4 ng/ml/year can be used as a criteria of when to initiate malignant work up.

Value:  This paper draws attention to an important segment of the population, men with lower total PSAs and how to risk stratify them for evaluation of PCA by using a PCA velocity that more reflects their disease.  This is a large community based study, and over a ten year period, and as such, criteria during the study were modified to increase the yield of prostate cancer findings. Overall, the paper brings value for clinical practice, as it supports inclusion of PSA velocity as indication to rule out malignant disease of the prostate, and not just an absolute total PSA or abnormal DRE (which is exactly what this study did!).  Also of value is that this study specifies a different PSA velocity with PSA values 0 to less than 4ng/ml, a population which had not been specifically been addressed in the past.  Limitiations include PSA velocity calculation from one year post diagnosis, and suggests that variability in data may be related to incidence of prostatitis.  Additionally, PSA velocity was not used as an indication for performing prostate biopsy.

The Smith Institute for Urology holds a monthly Journal Club  in order to review the latest breaking news in urology and ensure we are at the cutting edge of urologic care.  All of our urology physicians meet with our resident-physicians and review both our own publications and those from other institutions in the leading medical journals, inluding The Journal of Urology, Urology, The Journal of Endourology, The New England Journal of Medicine, and JAMA.

 It occured to us that the public has little access to the latest medical news, even though such information matters to them most.  So we thought that the The Smith Institute Blog would be a good avenue to get such information out to you, our patients for your review.  We will post brief reviews of current literature relating to all key urologic conditions.  In addition, we will give our thoughts regarding the relevance of the research and how it is likely to impact your care. Please Blog us with questions, or feel free to come in for an appointment to discuss further.

Lee Richstone, MD

Director of Laparoscopy and Robotic Surgery

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Over the last several years I have had patients with true urologic emergencies who sought medical attention too late.  By the time these patients came to medical attention, serious and irreversible harm had occurred. 

 A common sentiment among these men was that they were unaware that their symptoms were indicative of such a serious issue.  They all would say “nobody told me this was a problem”, or “they didn’t teach me that in health class”.   It occured to me that none of us get a good education regarding our bodies, and it would be nice if we all came with an instruction book or “user’s manual”!

Fortunately for urologists, there aren’t that many true urologic emergencies, but there are a few that all men should become aware of.  What better place to start getting such information out then the Smith Institute Blog?

Recently I had a patient come in who complained of diminished erections during sexual relations (Erectile Dysfunction, ED).  A detailed medical history revealed to me that he had an unusual event during sexual relations with his wife over a year prior to coming to my office.  During intercourse he heard a “popping” sound, his penis rapidly lost it’s rigidity (”detumescence”), and his penis became severely inflammed and ecchymotic (black and blue).   Of course, he wasn’t totally unaware that something significant was happening, and he did call a friend with some medical background.  Unfortunatley, the friend was incorrect in advising him to let it “cool down” on it’s own, and my patient had “never been told” about such an event.  This would be a great thing to include in 7th grade health class. 

My patient experienced a “penile fracture”.  To understand a penile fracture, we should review the “architecture” of the penis.  Under the penile skin there are three cylindrical structures that together comprise the bulk of the penile tissue and are responsible for erections.   They are the corpora cavernosa (2) and the corpus spongiosum (1).  Within the spongiosum is the urethra, or “water channel” through which a man urinates.  During sexual stimulation, the two corpora cavernosa engorge with blood, which is trapped within them, and the corpora become rigid. Thus, an erection is achieved.

 During vigorous intercouse, or if excessive force is applied to the penis in the wrong direction so that the penis sustains a so-called increase in axial load forces, the wall of the corpora cavernosa can crack or split.  The blood within the corpora rapid flows out and the erection is lost.  The blood that leaks out settles under the skin.   This process accounts for the “snapping sound”, rapid loss of erection, and black and blue appearance, respectively, that my patient experienced.  In some cases  the corpus spongiosum and the urethra within can also become injured.  This would be associated with blood at the tip of the penis, or with bloody urine.

A fractured penis is a urologic emergency that every man should be aware of.  Medical attention should be sought immediately through the emergency room.  A simple operation taking less than an hour can fix the problem and allow for complete recovery in the vast majority of men.  Allowing the penis to heal on it’s own results in a higher risk of erectile dysfunction, and/or penile curvature.

So, now you know!  Every man should be aware of this possibility and what to do should it occur. 

As one of the features on the Smith Institute Blog we will update you with other urologic emergencies so that you can optimize your overall and urologic health.

Regards,
Lee Richstone, MD

Director of Laparoscopy and Robotic Surgery 

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Welcome to The Smith Institute Blog (SIB)!  The central purpose of our blog is to provide patients and their families an opportunity to ask questions of our experts, and and further access to urology related information.

The urologists at the Smith Institute are at the cutting edge of all urological diseases, and we will keep you up to date on our clinical and research endeavours at regular intervals!

Regards,
Lee Richstone, M.D. 

Director of Laparoscopic and Robotic Surgery

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