To Treat or Not To Treat, Early Stage Prostate Cancer

Over 200,000 men will be diagnosed with prostate cancer this year. The majority of these men (90%) will have localized disease. It has been established that early prostate cancer is over diagnosed and over treated. The dilemma for most of these men will be whether to treat or not to treat.

The Scandinavian Prostate Cancer Group Study has provided evidence that after a median follow-up of 12.8 years, patients treated with surgery (prostatectomy) had a greater survival than patients treated with watchful waiting by about 5% (87.5% vs. 82.1%). Metastasis was also less likely to be found in the treated group by 6% (19.3% treated vs. 26% not treated). This survival benefit was restricted to men younger than 65 years of age, Gleason score <7.

This survival benefit may not be relevant in men identified by PSA screening, as in the Scandinavian study 88% of patients had palpable tumors, implying a more advanced stage. In the US the median age at diagnosis of prostate cancer is 67, fewer than 50% have palpable tumors, and the lead time associated with prostate cancer detection from PSA screening has been estimated to be as long as 10 years. The only reason to question therapy is the price one has to pay in side effects and decrease quality of life issues. Prostatectomy is associated with erectile dysfunction and urinary incontinence.

Advancements in the delivery of radiation therapy, including image guided and focusing techniques, have allowed for improvements in the rates of disease control similar to surgery. Large, randomized studies comparing the two modalities in early stage disease are lacking. Radiation therapy is associated with bladder irritability, bowel symptoms and at some point erectile dysfunction as well. Adjuvant hormone therapy, shown to benefit patients receiving radiation therapy, increases the side effect profile with vitality and hormonal function issues.

Treatment-related symptoms are exacerbated by obesity, large prostate size, high PSA score, and older age. These changes influence satisfaction with treatment outcomes in patients and their partners. In the end, the decision to treat or not to treat is a personal one with one’s urologist acting as coach. The question to ask: “…is the promised benefit at the end of the road worth the price paid in decrease quality of life en route?”

BPH (Benign Prostatic Hyperplasia)

Definition

The prostate is a sex accessory gland, whose function is to produce the seminal fluid, which is the transport medium for the sperm. It is situated around the urethra, like a doughnut, at the exit of the urethra from the bladder. BPH is an enlargement of the prostate gland whereby the number of cells increases through reduced cell death, under the influence of changing hormonal factors taking place with age.

The Role of BPH in Obstruction

The commonly held notion that the symptoms of BPH (poor flow, nighttime voiding) are caused simply by mass related effects are too simplistic. The lower urinary tract symptoms (LUTS) are caused by a combination of the effects of mass (glandular component), stromal tissue (the tissue between the glands) dysfunction as well as bladder muscle dysfunction.

Genetic and Familial Factors

There is evidence that BPH has a genetic component consistent with a dominant pattern. Men with familial BPH have larger prostate volumes (83 ml), compared with men with sporadic BPH (55 ml), and have a higher incidence of surgical intervention when younger than 60 years of age. However, small prostates can also be symptomatic when stromal factors predominate. In fact, the size of the prostate does not correlate with the degree of obstruction. Both active and passive forces play a major role in the obstructive symptoms and increased urethral resistance associated with BPH.

The Bladder’s Response to Obstruction

The bladder’s response to obstruction is an adaptive one and the changes are of two basic types:

  • Detrusor (bladder muscle) instability (decreased compliance) associated with symptoms of frequency and urgency
  • Decreased detrusor contractility – associated with progressive deterioration of urinary stream, hesitancy, intermittency, increased residual urine.

Diet, Obesity and BPH

A Health Professionals Follow-up Study indicated a possible correlation between abdominal obesity and increase in the frequency and severity of urinary obstructive symptoms and may increase the likelihood that such men will undergo a prostatectomy.

Medications

Cold medications, antidepressants, antihistamines or bronchodilators are associated with a 2-3 point increase in the AUA Symptom Index.

 

Complications of BPH

  • Bladder Stones
  • Urinary Tract Infections
  • Bladder Decompensation (loss of muscle function)
  • Urinary Incontinence
  • Upper Urinary Tract Deterioration and Renal Failure
  • Hematuria (blood in the urine)
  • Bladder Diverticula
  • Acute Urinary Retention (AUR)

PSA and BPH

BPH can increase the PSA and there is a direct volume based relationship. Studies have shown a predictive correlation between PSA and AUR (acute urinary retention). In a 2-year study the rate of AUR was eightfold higher in those with a serum PSA of over 1.4 ng/ml (0.4% vs. 3.9%), and threefold higher if the prostate volume was over 40 ml (1.6% vs. 4.2%). An analysis of over 100 possible outcome predictors alone or in combination revealed a combination of serum PSA, urinating more than every 2 hours, symptom problem index, maximum urinary flow rate, and hesitancy as being only slightly superior to PSA alone in predicting AUR episodes.

Treatment for BPH

Non-symptomatic BPH does not require treatment. Symptomatic BPH treatment frequently correlates with the degree and severity of the symptoms and other correlated issues such as kidney function, the degree of urinary retention, prostate size, and patient co-morbidities. Medications, like alpha-blockers, provide the quickest response in symptom relief. 5 alpha-reductase inhibitors work on decreasing prostate volume, but they can take up to 3 months to show a benefit and sometimes longer. They tend to work best in prostates over 40 ml. in volume. Minimally invasive office treatments, like TUNA, use radiofrequency energy to heat the tissue and reduce the prostate volume. Finally, the proverbial “gold standard” is the TURP (trans-urethral resection of the prostate), which removes obstructive tissue to allow for a freer flow of urine.

The Prostate Story

The prostate has become a common focus of discussion in health related media outlets, but it would not be wrong to assume that most people don’t know what the prostate is. The prostate is a male reproductive organ about the size of a golf ball, growing around the urethra (the urinary channel) as it leaves the bladder. Its function is to make semen, the nutrient fluid in which the sperm lives.

The prostate can be the cause of many problems in men and the consternation is compounded by the confusion surrounding the media cacophony about screening for prostate cancer and the usefulness of PSA (prostate specific antigen) in this regard. Prostate cancer is one of the most commonly diagnosed cancers among men in the United States. Prostate cancer is not only prevalent, but also slow growing. Only 0.6% of diagnosed prostate cancer patients die within 5 years. (NCI SEER data) This makes it difficult to decide how and if to treat the prostate cancer. The main question becomes: is the cancer significant enough to require treatment? Not all prostate cancers are the same. Age, Gleason score, stage, co-morbidities, all contribute to outcomes. The AUA has come out publicly with the statement that prostate cancer is over diagnosed and over treated and active surveillance is an acceptable option.

The main marker used to screen for prostate cancer is the PSA. However this elevated in benign conditions as often as it is in the presence of prostate cancer. The PSA is a protein made by prostate cells, which can be found in increased amounts in the blood in conditions where the vascularity of the prostate increases. This can occur in both malignant as well as inflammatory conditions, as in prostatitis. The PSA is not diagnostic of prostate cancer, but taken in context with other clinical information obtained during evaluation, can help in diagnostic and treatment related decision-making by experienced physicians.

Although there is debate regarding the role of diet in prostate cancer, some clear trends have emerged:

  • Prostate cancer rates vary widely between countries and ethnicities.
  • Prostate cancer rates are higher in societies with “Western” diets and lifestyles.
  • These higher cancer rates follow the adoption of Western eating practices.

Prostate cancer has been shown to have a genetic component with a three-fold increase in incidence in first-degree relatives. However, environmental factors also play an important and possibly a decisive role in the appearance of this disease. There is a three-fold increased incidence in prostate cancer between Asians (88/100,000) and Blacks in the US (233/100,000). What are the main dietary differences between Western and developing countries? The emphasis is on animal-based foods in the former, versus plant-based foods in the latter.

There is a large amount of evidence pointing to animal derived fat as playing a role in the development of prostate cancer. What are the mechanisms for this? The first mechanism involves a hormone that increases cancer cell growth. This is a growth hormone called Insulin-like Growth Factor 1 (IGF-1). It turns out that consuming animal-based foods increases the blood level of this growth hormone.

Vitamin D metabolism has also been implicated in prostate cancer. Our bodies can make all the Vitamin D we need by exposure to the sun. This Vitamin D gets transformed to the active form 1,25 D in the kidney. This active form of Vitamin D is 1,000 times more active than the non-active form, and acts in preventing cells in becoming diseased. Animal protein-containing foods cause a significant decrease in 1,25 D. Another cause of decreased 1,25 D is too much calcium in the diet. All these variable pathways can interact in unexpected ways to lead to adverse effects in these intricate networks. The take home-message regarding diet, to quote Michael Pollan, the healthy food advocate:
“Eat food. Not too much. Mostly plants.”

Urinary Tract Infections

Definitions

Urinary Tract Infections (UTI) –  are caused by the presence of bacteria in the urine (bacteriuria), which is normally free of bacteria.

Pyuria - The presence of white blood cells (WBC’s) in the urine, indicative of an inflammatory response to bacterial invasion.

Acute Pyelonephritis - is a clinical syndrome of chills, fever, and flank pain that is accompanied by bacteriuria and pyuria, indicating an acute infection of the kidney.

Chronic Pyelonephritisdescribes a shrunken, scarred kidney, secondary to recurrent inflammatory insults over various periods of time.

Cystitis is inflammation of the bladder, whether bacterial or otherwise. Bacterial cystitis as opposed to nonbacterial cystitis can be a useful differentiating term.

Urethritisthis refers to inflammation in the urethra, rather than the bladder. Symptoms from one are very difficult to differentiate from the other. Pure urethritis in the female – unlike that in the male – is very rare.

Recurrent Infections are due to either reinfection with a new organism after an infection-free period, or to bacterial persistence or recurrence caused by the same organism from a persistent focus within the urinary tract.

Most Common Causes of Persistent UTI

  • The infective organism is resistant to the antibiotic selected
  • The development of resistance in a previously susceptible organism
  • Poor renal function, which prevents antibiotic concentration in the urine
  • The presence of stones or abnormal tissue leading to high concentrations of bacteria
  • Urinary reflux
  • Predisposing genetic factors that increase chance of bacterial attachment to host
  • Chronic bacterial prostatitis (infection of the prostate)
  • Foreign bodies
  • Urethral diverticula and infected urethral glands
  • Fistulas to the bladder from colon or other infectious collections

Routes of InfectionMost bacteria enter the urinary tract from the fecal reservoir in a retrograde manner, via ascent through the urethra into the bladder.

Bacterial Adherence and ColonizationStudies have demonstrated that for infection to occur bacteria have to adhere to host tissue and this is done through hair-like protein appendages on bacteria called pili, which adhere to receptor sites on cells. The virulence of bacteria depends on the strength of this interaction, which is affected by both bacterial and host factors and maybe genetically determined.

Principles of Antimicrobial Therapy

Initial Elimination of BacteriaElimination of bacteria occurs within hours if the proper antimicrobial agent is used.

Duration of TherapyIn women with uncomplicated UTI’s, 3 days of full-dose therapy has been shown to be as effective as longer courses. In the presence of mitigating circumstances, such as recurrence, chronicity, age older than 65, diabetes or pregnancy, a 7-day regimen should be considered. In complicated infections, or infections of the kidney, 14- to 21-day regimens should be used.

Asymptomatic Bacteriuria (the presence of bacteria in the urine)Older people frequently have this condition, without the symptoms of a UTI. This condition does not require treatment in the absence of symptoms. Treating these patients only clears their urine of bacteria for short periods and then they become recolonized. Multiple treatments lead to the development of resistant organisms.

Factors Increasing Severity of Infection

  • Urinary obstruction
  • Renal or bladder stones
  • Catheter drainage
  • Diabetes
  • Spinal cord injury or neurogenic bladders
  • Pregnancy
  • Acute bacterial prostatitis (prostate infections)

Bladder Infections

Uncomplicated Cystitisclinical symptoms include dysuria (burning), frequency, urgency, voiding of small volumes, or sensation to void without much urine, and suprapubic and lower abdominal pain. The presumptive diagnosis can be made on urinalysis, but urine culture remains the definitive test. Short course of antibiotic therapy adequate in women with uncomplicated infections, but should be avoided in men.

Reinfectionscause has to be identified and corrected. Specific risk factors have been identified for reinfections in women, including the first UTI before age of 15 years and maternal history of UTI’s. In women, diaphragm-spermicide and tampon use have been associated with increase risk of UTI and vaginal colonization with E. coli bacteria. Spermicides containing the active ingredient nonoxynol-9 may provide a selective advantage in reducing colonization. Thus, spermicidal agents should be discontinued in women with recurrent UTI’s.

Postmenopausal women have frequent reinfections. Estrogen replacement frequently restores the normal vaginal environment.

Low-Dose Prophylaxislong term, low-dose therapy can be given to prevent reinfection. The success of prophylactic therapy depends on the effect of the antimicrobial agent on the vaginal and fecal reservoirs of pathogenic bacteria. One a day dosing for 6 weeks is a common regimen. In some cases 6-12 months are needed.

Post-Intercourse Prophylaxissexual activity has been established as an important risk factor for acute cystitis in women. Post-intercourse therapy with antimicrobials in women with “honeymoon cystitis” taken as a single dose post intercourse reduces the rate of infection.

Urinary Tract Infections During Pregnancybecause pregnant women with bacteriuria are at an increased risk to develop kidney infections, this should be looked for and treated when found. Selection of an antibiotic to treat the bacteriuria must be made with special consideration to maternal and fetal toxicity.

Erectile Dysfunction (ED)

Erectile dysfunction is defined as the inability to achieve, or maintain an erection, sufficient for completing the sex act. It is a common ailment, increasing in frequency with age, affecting approximately 30 million people in the U.S.

Due to embarrassment, many men avoid raising this issue with their physicians, and prefer to suffer in silence. This is unfortunate, as there are many good forms of treatment for this condition. Moreover, loss of erections can be a signal for other serious medical illnesses, such as vascular disease, diabetes, or coronary artery disease.

Mechanism of Erection

Erection is achieved by a complex mechanism, which regulates inflow and outflow of blood from the penis. With arousal, hormone and chemical transmitters increase blood flow to the genital region, while limiting the blood flow to other areas not involved in the arousal process. As the penis expands, pressure inside the penis increases and compresses veins, which carry blood away from the penis. This process leads to full erection until maximal pressure is achieved. After ejaculation, or with loss of erection, blood flow to the penis decreases, and as the pressure inside the penis goes down, the veins allowing for blood to flow away from the penis open up and the penis becomes flaccid.

Causes of ED

  • Diabetes – No.1 cause of ED in the U.S. This is caused by the effect diabetes has on blood vessels.
  • Elevated Blood Pressure – and the medications used to treat hypertension.
  • Heart Disease
  • High cholesterol
  • Certain Medications – cardiovascular, tranquilizers, and antidepressants
  • Cigarette smoking – also affects blood vessels.
  • Excessive alcohol – “gives the desire, but takes away the performance”.
  • Stroke, or neurological diseases (Alzheimer’s, MS, Parkinson’s).
  • Pelvic Surgery – radical prostate surgery, including robotic surgery.
  • Radiation therapy to treat prostate or rectal cancer.
  • Trauma to the pelvic area.

Use It or Lose It

Research indicates that men who remain sexually active report a decrease incidence of ED, which is directly related to the frequency of sexual activity. Occasional decrease in sexual performance, can be experienced by normal men, which can trigger a significant psychological reaction. This can lead to performance anxiety, depression or loss of confidence. Men can start avoiding sexual encounters for fear of failure. The fear factor causes vasoconstriction to areas unrelated to systems tied into defense mechanisms. This can spiral into psychological impotence. Being relaxed, and unconstrained by distracting thoughts allows for normal erections to occur. Having morning erections, is an indication of a working erectile mechanism.

When Treatment is Necessary

When organic causes are diagnosed to be the cause of ED, the options are good when delivered under the care of physicians who specialize in this area.

Oral medications are extremely effective in achieving erections and work in about 75% of people who use them. Drugs like Viagra, Cialis and Levitra have become part of the cultural lexicon and are frequently advertised in the media. A major downside is the high cost of therapy.

Other treatment options include Muse – a urethral insert, which is absorbed through the mucosa of the urinary channel. Penile injection therapy, which is not difficult to use, given a small amount of patient cooperation. Vacuum erection devices, which can work by itself, or in combination with some of the oral or injectable medications.

When all else fails, penile prosthesis is a reasonable option, which can restore a man’s sexual function and maintain an active sex life and satisfactory relations with his partner. This is a hospital procedure, which lasts about 1 hour, and introduces an implant, which can be controlled through a pump mechanism in the scrotum. Patients continue to experience normal ejaculation and orgasm.