Clinically Localized Prostate Cancer

Statistics: Prostate cancer is the most common cancer in U.S. men with approximately 218,850 new cases expected in 2007. Prostate cancer is expected to kill 27,050 American men in 2007, third behind lung cancer and colorectal cancers. The death rate from prostate cancer has declined by about 30% in the past 15 years as a result of early detection and improved treatment. While nearly 40% of U.S. men will develop some form of prostate cancer, many will not be diagnosed with or die from this cancer.

Natural history: Prostate cancer grows locally within the prostate and eventually invades into nearby tissues (bladder, seminal vesicals, muscles and fat). When it spreads, it typically goes to lymph nodes and bone, and later to other organs. When it spreads well beyond the prostate, survival is reduced and cure improbable.

Prostate cancer is graded based upon its microscopic appearance. Well differentiated tumors somewhat resemble normal prostate and behave less aggressively than poorly differentiated tumors, which barely resemble normal prostate glandular tissue. The Gleason Score is from 2 (well differentiated) to 10 (poorly differentiated). A tumor’s Gleason Score can be used to predict how that particular cancer will behave. The prostate specific antigen blood test (PSA) can be normal or elevated, but markedly elevated PSA values are less favorable than lower PSA levels. When the Gleason score, PSA, recent rate of PSA increase (termed PSA Velocity), clinical stage (finding on digital rectal examination (DRE) and prostate ultrasound) are combined, an impression can be made regarding expected outcome of treatment options. Low grade, low stage cancers take longer to impact on an individual’s life than high grade or high stage tumors. Marked individual variance in tumor behavior commonly occurs, thus long-term predictions or prognoses are often inaccurate. ‘Clinically localized prostate cancer’ refers to a cancer that appears to be confined to the prostate and, therefore, potentially curable. To avoid prostate cancer morbidity and mortality, both early detection and effective treatment must be accomplished.

Treatment considerations: Since men are often older (60’s, 70’s, 80’s) when prostate cancer is diagnosed, and some tumors are relatively slow growing, the relative morbidity of prostate cancer must be weighted against expected survival from other life-limiting illnesses. For example, a man with significant heart disease that is expected to live less than 5-6 years may not want to aggressively pursue curative therapy for a low stage, low grade prostate cancer that will not cause significant problems for 5-7 years or more. The same tumor in a man with less threatening medical problems who is likely to live longer might consider curative treatment to prevent cancer-related complications or even death from prostate cancer. Factors that make treatment decisions difficult include: uncertain life expectancy, unpredictable tumor behavior, variable incidence of treatment related complications, inaccurate clinical staging and therefore, unpredictable treatment effectiveness. Once the cancer spreads away from the prostate, cure is not considered possible.

Active Surveillance: In patients with low grade, low stage cancers and a limited life expectancy; periodic monitoring of the PSA, DRE, overall symptoms and periodic restaging ultrasound and biopsy can track the behavior of the cancer. Watchful waiting without curative treatment risks complications of disease progression, but avoids treatment related risks in the short-term. For men without prostate related symptoms and a cancer that does not appear to pose a threat in the anticipated future, watchful waiting may be a suitable management approach. The problems with watchful waiting are related to our relative inability to accurately assess the time that a specific cancer will take to cause problems, and, once the cancer shows signs of aggressive behavior, the chance for cure is often lost. There is less short-term risk and more long-term risk if life expectancy or cancer aggressiveness is underestimated.

Hormone manipulation: Elimination of testosterone (made in the testicles) by either removal of the testicles or suppression with hormone shots usually causes prostate cancer to go into remission for several years. This form of therapy has not been found to be curative but sometimes offers cancer control for longer than the typical 2-3 years. Side effects of testosterone removal (by either method) may include hot flashes, loss of libido, loss of potency, mild anemia, reduced energy, reduced muscle tone, earlier osteoporosis, cognitive (thought) changes and occasionally subtle mood changes. Most men note significant alterations in their bodies while on hormone therapy. Hormone therapy is generally used when the initial management approach (radiation, watchful waiting or surgery) fails.

Radiation therapy: Radiation therapy attempts to destroy cancer cells without seriously harming normal, adjacent tissues. Radiation can be delivered to prostate tissues by either external beam treatments (daily treatments for 8 weeks) or by surgically implanting permanent or temporary radiation ‘seeds’ into the prostate gland (1 - 2 hour outpatient surgical procedure). These treatments have similar side effects and fairly similar success rates. A patient with a small gland without urinary symptoms, a small volume of cancer, a PSA less than 10 and a Gleason score of 6 or less may be a candidate for one type of radiation. Less favorable cancer characteristics may require a combined approach including more than one type of radiation with or without temporary hormone therapy. Men with larger glands or prior prostate surgery are more likely to have significant urinary side effects including incontinence. Other methods of radiation such as neutron beam and proton beam therapy are still considered investigational and are available at a few research centers.

Side effects are generally grouped into short-term irritation from radiation and long-term tissue effects of radiation. Short-term effects are related to tissue irritation and usually resolve within several months of external beam therapy and longer (1-2 years) after seed implants. Some short-term effects include urinary frequency, urgency, blood in urine, burning with urination, night-time voiding, small bladder capacity, diarrhea, urgency for bowel movements, blood in stool, mucus drainage from the anus, fatigue and skin changes. Long-term effects usually do not start becoming noticeable for at least 2 - 3 years after treatment and typically worsen as time passes. The symptoms are similar to the short-term effects but also include tissue scarring, urethral and/or rectal strictures (scar narrowing the tube), incontinence of urine and stool, impotence, anal and urinary sphincter problems. Recent studies utilizing patient reported results regarding important quality of life issues reveal that significant urinary incontinence and irritative urinary and bowel problems increase after 3 years in patients undergoing all forms of radiation. Impotence is usually preserved initially, however, after several years, impotence may be more common than seen after well done nerve sparing surgery. Chronic radiation changes complicate normal tissue healing and resistance to infection, which can significantly complicate otherwise straightforward surgical procedures, should future surgery be necessary. In recent years, increased incidence of invasive rectal and bladder cancer are seen in previously radiated men. While many patients treated with radiation do fairly well for 4-8 years, late complications of radiation and recurrence of prostate cancer is a common problem for those who live longer.

Cryotherapy: Cryotherapy is the controlled freezing of the prostate. Cryotherapy more effectively ablates (destroys) the cells (benign and cancerous) in the prostate. Recent technological advances in prostate cryotherapy have lead to renewed interest in this treatment option. Today, cryotherapy is more effective at ablating the prostate than radiation. Additionally, cryotherapy can be done without harming the bladder and rectum. If an initial treatment with cryotherapy is found to be incomplete, it can safely be repeated – an option not possible after radiation fails. Cryotherapy is performed as an outpatient under anesthesia in the operating room. A catheter is left in the bladder for one week after therapy and post-treatment PSA levels should be undetectable in successful cases. While men generally have improved voiding after cryotherapy and incontinence rates are 2 – 6%, impotence is almost universal. Modern cryotherapy has less long term risk than radiation, but is less effective than surgery.

HIFU (High Intensity Focused Ultrasound): HIFU is the newest minimally invasive treatment for localized prostate cancer. It is an outpatient procedure done in the operating room under anesthesia. HIFU focuses a tissue heating energy in the prostate causing ablation of the tissue. While HIFU is available in very few research centers in the United States, it is available in Canada and Mexico. Some prostate cancer specialists (including Dr. Harris) have direct access to this technology through arrangements. While incontinence is uncommon and potency often preserved, it is less effective compared to surgery done by the best surgeons.

Radical prostatectomy: The surgical removal of the prostate and seminal vesicals is the gold standard for treatment of localized prostate cancer. Radical prostatectomy can be accomplished through an abdominal incision (radical retropubic prostatectomy - RRP), through a perineal incision between the scrotal sac and the anus (radical perineal prostatectomy - RPP) or by a laparoscopic approach with six finger-sized holes puncturing the abdominal wall into the pelvic area. Most laparoscopic prostatectomies are done with the assistance of a robotic instrument between the surgeon and the patient as robotic instruments have a greater range of motion inside the patient than conventional laparoscopic instruments (robotic assisted laparoscopic prostatatectomy or RALP).

The primary goal of all techniques is to remove the prostate and seminal vesicals intact without violating the cancer while minimizing injury to urinary and sexual function. While the most common approach has been the RRP, in recent years, minimally invasive methods (RPP and RALP) have been gaining popularity as these advanced techniques are being disseminated in the urologic world. In 1992, Dr. Harris co-authored a new minimally invasive technique of RPP that optimizes cancer control while maximizing urinary function and control as well as preserving potency through nerve-sparing. The main advantages of RPP are the shorter surgical time, overnight hospital stay, limited blood loss, minimal post-operative discomfort and a short recovery period. Since moving to Traverse City in 1993, Dr. Harris has built one of most comprehensive outcomes research programs with a massive database of his prostatectomy patient outcomes. By studying the actual results and comparing results following minor technical modifications, Dr. Harris has fine-tuned the procedure to be one of the most technically advanced methods of prostatectomy available anywhere. The recent literature in prostate cancer research has identified the surgeon as the most important variable influencing an individual patient’s results. It is clear that the approach is less important than the surgeon. However, the RPP combines the best of all available techniques and is versatile in the most challenging patient situations.

The RPP operation takes about 80 minutes and can be performed under a general or spinal anesthetic. After a one-hour visit to the recovery room, patients go to the urology floor where they resume eating and walking on the same day as surgery. The nursing staff educates the patient on post-operative care. Most men are home by lunchtime on the day after surgery. Activities are unrestricted when the catheter is removed, 8 days after surgery. The PSA is typically undetectable when measured 2 months later.

Results vary from surgeon to surgeon and by technique used. Dr. Harris provides up-to-date outcomes data to potential patients as they apply to the unique situation as it applies to his case. In general, over 90% have undetectable PSA, while patients with more favorable, organ-confined cancers have a 95% chance of an undetectable PSA long-term. Patients with more advanced tumors have a higher risk of relapse, typically due to microscopic sites of cancer spread that are unrecognizable prior to surgery. While many men have some urinary leakage soon after surgery, over 50% are dry by one month and ultimately over 98% regain natural control. Treatment options are available for the few men who do not regain satisfactory control. Men with some prostate enlargement usually void with a more forceful stream and an improved urinary pattern than before surgery. Appropriate candidates for erectile nerve preservation have a good chance at recovering adequate erections. Blood transfusions are no longer necessary. There are very few other complications. While not completely recovered, most men resume usual activities within 2 weeks of surgery.

Summary: The most important step a man with newly diagnosed prostate cancer can do is to adequately study the personal results of any physician he consults with to treat his cancer. After initial therapy, salvage options are relatively limited if suboptimal results are obtained. The table below provides a brief comparison of the above treatments that are intended to cure prostate cancer. The results are based upon the best physician’s experiences in each technique.

Treatment type	Cancer control	Voiding function	Potency	Other issues
Radical Perineal Prostatectomy	Best: complete removal of the prostate	Better voiding pattern, initial leakage, 3-8% incontinence at 1 year, no long-term worsening	40-70% at one year, 60-90% by two years, then age-related decline	Pro: Definitive, safe, least expensive, most versatile & least invasive surgery, no transfusions, short recovery Con: Few expert surgeons
Radical Retropubic Prostatectomy	Best: complete removal of the prostate	Better voiding pattern, initial leakage, 5-8% incontinence at 1 year, no long-term worsening	40-70% at one year, 60-90% by two years, then age-related decline	Pro: Definitive, safe, fairly inexpensive, many expert surgeons, Con: Long recovery, 2-10% transfused
Robot-assisted Laparoscopic Prostatectomy	Best: complete removal of the prostate	Better voiding pattern, initial leakage, 4-8% incontinence at 1 year, no long-term worsening	40-70% at one year, 60-90% by two years, then age-related decline	Pro: Definitive, fairly safe, short recovery Con: Fairly expensive, new, very difficult, least versatile surgery
External Beam Radiation-XRT	Fair: Benign & cancerous glands often survive, highest recurrence rate	Minimal short-term, gradually increasing bother symptoms & leakage	70-100% at one year, accelerated decline after 3 years	Pro: Least invasive, painless Con: Recurrent cancer common & difficult to treat, fairly expensive, second cancers (rectum, bladder), progressive toxicity
Permanent Radiation seed Implant alone	Good: Cancer control almost as good as removal	Significant short-term bother, progressive long-term bother & leakage, scarring	90% at 1 year, 40% at 6 years, accelerated decline after 3 years	Pro: good cancer control Con: Salvage therapy is compromised, very difficult to manage progressive toxicity, second cancers (rectum, bladder), expensive
Temporary Radiation seed Implant & XRT	Good: Cancer control almost as good as removal	Significant short-term bother, progressive long-term bother & leakage, scarring	80% at 1 year, 35% at 6 years, accelerated decline after 3 years	Pro: good cancer control Con: Salvage therapy is compromised, very difficult to manage progressive toxicity, second cancers, very expensive
Permanent Radiation seed Implant & XRT	Good: Cancer control better than seeds or XRT alone	Significant short-term bother, progressive long-term bother & leakage, scarring	80% at 1 year, 35% at 6 years, accelerated decline after 3 years	Pro: good cancer control Con: Salvage therapy is compromised, very difficult to manage progressive toxicity, second cancers, very expensive
Cryotherapy	Good: Better than radiation, worse than removal	Initially worse, then improved voiding pattern, 4% incontinence	0-5% immediately, 10% recovery after 1 year	Pro: Repeatable, safe, minimal risk to nearby tissues, fairly inexpensive Con: Impotence, less effective than removal
High Intensity Focused Ultrasound-HIFU	Fairly good: Similar to XRT, worse than removal	Initially worse, then improved voiding pattern, 1% incontinence	60-80%	Pro: Repeatable, safe, outpatient, minimal risk to nearby tissues Con: Not FDA-approved, new, costly