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Urology (Expert Forum)
Deciding on treatment
Answered by
Kevin Pho, MD - Internal Medicine
KevinMD.com
Questions in the Urology forum are answered by Dr. Stephen Liroff, affiliated with the Henry Ford Hospital. Topics covered include benign prostate disease, penis curvature, cystisis, kidney stones, pediatric urology, prostate, sexual dysfunction, urinary tract infections (UTI), and urological cancers.
Deciding on treatment
by Phillyboy, Dec 16, 2003 12:00AM
I need help with a man's most difficult decision: what form of treatment to choose for prostate cancer. My details are as follows. Age: 69, Health: very good, no chronic conditions, not overweight or a smoker. Most recent PSA = 2.9, % free PSA = 12%. 12-needle biopsy staged at 7 (3+4) by 1 pathologist, and at 6 by a second. 5 positive areas, all on one side, no positive areas on other side. There is a palpable area on the one side with cancerous cells. The worst parts of my prostate are the 2 lowest areas. My dilemma, not unique I know, is that after reading several books and looking at many internet sources, I am torn between choosing the surgical treatment (a nerve-sparing retropubic radical prostetectomy) and a very focussed conformal radiation treatment + seeds to be followed by hormonal treatment for 4 months to 2 yrs. Both of these treatments would be performed by very skilled and very experienced specialists at excellent hospitals. Each specialist recommends his modality of treatment, but says the other is a reasonable choice too!
I think I am a generally good risk for surgery, and can take the time for recovery. Of course I am attracted by the lesser down-time that radiation treatments involve. I know that you can't tell me what to do, but can you tell me what to consider as the benefits, risks and long-term considerations in making this decision? Is there something in my particualar case In terms of the best and current data, what are the differences in side-effects of the treatments for a patient like me? What are the long-term recurrence and survival data? What should I consider in weighing the pros and cons? I would greatly appreciate all the suggestions you can provide to help me with this excruciatingly difficult decision.
I think I am a generally good risk for surgery, and can take the time for recovery. Of course I am attracted by the lesser down-time that radiation treatments involve. I know that you can't tell me what to do, but can you tell me what to consider as the benefits, risks and long-term considerations in making this decision? Is there something in my particualar case In terms of the best and current data, what are the differences in side-effects of the treatments for a patient like me? What are the long-term recurrence and survival data? What should I consider in weighing the pros and cons? I would greatly appreciate all the suggestions you can provide to help me with this excruciatingly difficult decision.
Doctor's Answer
by Kevin Pho, MD, Dec 18, 2003 12:00AM
, Dec 18, 2003 12:00AM
To answer this question, I am going to paste an article from UptoDate, which provides answers to the questions you are asking.
Patient information: Treatment for early prostate cancer
Eric A Klein, MD
Cleveland Clinic Foundation and Taussig Cancer Center
Prostate cancer is a malignancy of the prostate gland, an organ that forms a ring around the urethra (the tube that carries urine from the bladder to the outside of the body) near its connection to the bladder. Prostate cancer is the most common cancer affecting men. Every year, approximately 189,000 men are diagnosed with prostate cancer in the United States, and 30,200 die from this disease. Over the last decade, the increasing use of prostate cancer screening by measurement of blood levels of prostate-specific antigen (PSA) has led to more cases being diagnosed at an early stage, when the cancer is still restricted to the prostate gland, and highly curable.
There are three standard approaches to treating early prostate cancer: surgical removal of the prostate gland, radiation therapy with or without hormone therapy, and "watchful waiting," a term that describes the decision to delay definitive treatment while carefully monitoring the patient for evidence of progression or growth of the cancer. Hormone therapy has traditionally been reserved for men with advanced or metastatic prostate cancer, although new applications of hormonal therapy as a supplement to watchful waiting, surgery, or radiation show some promise.
The ultimate choice of treatment is dependent upon several factors.
The likelihood that the prostate cancer is confined to the prostate gland and therefore, potentially curable
A man's age and overall health, including any other medical conditions
The outcomes and potential side effects associated with the different forms of treatment
Here we will discuss the pretreatment evaluation of men with early prostate cancer, and describe the available treatment options, outcomes from therapy, and treatment-related side effects.
PRETREATMENT EVALUATION — Prior to selecting the best treatment option, it is critically important that the extent of the prostate cancer be correctly determined. Although the true local extent of involvement can only be determined by surgical removal, several pretreatment factors can be used to predict whether a prostate cancer is likely to be confined to the prostate gland itself (termed organ-confined disease) or spread beyond the prostate gland, and therefore, more advanced. The most important pretreatment factors that determine outcome are the clinical stage, the level of the serum PSA, and the degree of aggressiveness of the tumor, referred to as the Gleason grade.
Prostate cancer stage — Physicians use a common notation to describe the extent, or stage of a cancer. The tumor-node-metastasis (TNM) system is the most common method used to stage prostate cancer (show table 1). Within the TNM system, T1 tumors are microscopic, and cannot be felt by the physician on rectal examination; T2 tumors can be felt with a rectal examination, but appear to be confined to the prostate gland; T3 tumors have grown beyond the prostate into the capsule of connective tissue that surrounds the gland, or into the seminal vesicles (glands near the prostate that secrete fluid into the reproductive tract); T4 tumors have grown locally beyond the prostate, and involve nearby tissues. The finding of a T3 or T4 tumor suggests a more advanced tumor that is not likely to be cured, even with aggressive surgery. It should be noted that the stage that is assigned by a rectal examination is termed a clinical or "c" stage, while a man who has undergone surgical removal of the prostate with microscopic evaluation will be assigned a pathologic, or "p" stage.
Endorectal coil MRI — A new x-ray method called endorectal coil MRI uses magnetic resonance imaging to assess the prostate and its surrounding tissues. Although this technique is not yet widely available, it appears to be particularly helpful in evaluating the possibility of extension outside of the prostate capsule or into the seminal vesicles in men who are considering surgery.
Serum PSA level — The vast majority of men with prostate cancer have elevated levels of PSA in the blood. The level of PSA at the time a prostate cancer is diagnosed provides important information as to the likelihood of finding organ-confined disease. As PSA levels increase, the likelihood of disease spread to tissues beyond the prostate gland rises. Men with a PSA concentration less than 10 ng/mL have a 70 to 80 percent chance of having organ-confined disease, compared to 50 percent for those with PSA levels 10 to 50 ng/L, and only 25 percent with higher PSA levels [1]. Because of this, men with PSA levels above 10 ng/mL are usually recommended to undergo a CT scan of the abdomen and pelvis, and a bone scan prior to treatment in order to detect any spread of tumor to the pelvic and abdominal lymph nodes, or bones.
The pretreatment PSA level can also predict the likelihood of a cancer recurrence after treatment. Men with a lower PSA concentration are more likely to be cancer-free five years after treatment than those with a higher pretreatment PSA level.
Biopsy grade — A prostate biopsy, in which a small amount of tissue is removed from the prostate and examined under a microscope, is typically performed when prostate cancer is suspected. this examination allows the physician to confirm the diagnosis, and also assess the level of aggressiveness (the Gleason grade) of the tumor.
The pathologist typically reports a primary grade (between 1 to 5) and a secondary grade, also between 1 and 5. The higher the Gleason grade, the more aggressive (fast-growing) the tumor appears. These two numbers are then combined together to form the Gleason score. If the cancerous tissue shows primarily grade 3 and secondarily grade 4 areas of tumor involvement, the combined Gleason score is "3 plus 4" or 7. Gleason score 2 to 4 tumors are typically referred to as low grade (also called well-differentiated), Gleason 8 to 10 tumors are high grade (or poorly differentiated), and the Gleason scores between 5 to 7 are referred to as intermediate grade.
Predictive models — These pretreatment factors, and combinations of these factors can be used by physicians in two ways: they are useful to predict the likelihood that a man has an organ-confined cancer that may be potentially curable, and they can also be used to predict the outcome of either surgery or radiation therapy.
Predicting organ-confined cancer — The use of combinations of these pretreatment factors is more accurate than any one of the individual factors to predict the likelihood of a man having organ-confined disease. One such predictive model combines the clinical tumor (T) stage, the Gleason score from the tumor biopsy, and the serum PSA to construct tables that allow an estimation of the likelihood of finding organ-confined, and thus, potentially curable disease at the time of surgery (show table 2).
Predicting treatment outcome — In addition to predicting the likelihood of organ-confined disease, pretreatment models utilizing PSA, biopsy Gleason score, and clinical T stage can also be used to predict the chance of being cancer-free following either surgery or radiation. In general, these models stratify patients into one of three defined prognostic groups:
Low risk — Clinical stage T1c or T2a, serum PSA concentration <10 ng/mL, and biopsy Gleason score 6 or less. Men with low risk disease have a greater than 85 percent chance of being cancer-free five years after treatment with either surgery or radiation therapy.
Intermediate risk — Clinical stage T2b, serum PSA 10 to 20 ng/mL, and a biopsy Gleason score of 7. Men with intermediate risk disease have approximately a 50 percent chance of being cancer-free at five years after treatment.
High risk — Clinical stage T2c disease, serum PSA >20 ng/mL, and a biopsy Gleason score of 8 or higher. High risk patients have an approximately 33 percent chance of being cancer-free five years after treatment.
TREATMENT OPTIONS FOR EARLY PROSTATE CANCER — The three standard therapies for men with organ-confined prostate cancer are surgery (radical prostatectomy), radiation therapy, and watchful waiting. To date, no good study has directly compared these three options. Young, healthy men are typically encouraged to undergo radical prostatectomy, while older patients tend to be steered toward radiotherapy or observation. This fact makes it difficult to compare outcomes in men treated with either surgery or radiation.
Radical prostatectomy — Radical prostatectomy entails a complete removal of the prostate gland. This treatment option is thought to offer the best chance for long-term survival (beyond ten years). Men with low-risk early stage prostate cancer who undergo radical prostatectomy have an 80 to 85 percent chance of remaining cancer-free up to 15 years after surgery.
During a radical prostatectomy, the surgeon removes the entire prostate and then reconnects the urethra and bladder. The prostate gland may be removed from two different approaches: the perineal approach, or the retropubic approach. One advantage of the retropubic approach is that it allows tissue to be removed from the lymph nodes within the pelvis prior to surgical removal of the prostate. This lymph tissue is then evaluated for evidence of tumor spread (termed nodal metastases); the prostate gland is removed only if the lymph nodes are free of cancer.
Complications — Serious or life-threatening complications from radical prostatectomy are rare. The most common complications are urinary incontinence (uncontrolled leakage of urine) and sexual impotence (the inability to have an erection sufficient for sexual intercourse). Advances in technique in recent years have reduced the incidence of both these conditions by sparing the nerves responsible for urinary and sexual function, although a nerve-sparing prostatectomy is not possible in all men. Nerve-sparing surgery is not usually recommended for men who have large tumors, high Gleason grade cancers, or a high PSA before treatment. For other men with prostate cancer, there is no evidence that a nerve-sparing operation compromises control of the cancer.
The majority of men are incontinent and impotent immediately following surgery. However, both tend to improve with time after surgery. Age is an important factor in the risk of urinary incontinence after prostatectomy. In a large study that monitored over 1,200 men for two years after surgery, extreme urinary incontinence was experienced by almost 14 percent of men between 75 and 79, but in fewer than 4 percent of younger men [2]. Almost one-half of the affected men had only occasional urinary incontinence, often related to stresses on the bladder such as sneezing, coughing, or laughing.
The likelihood of experiencing sexual impotence after radical prostatectomy also increases with age. In one review, the potency rate after surgery was 100 percent for men in their 40s, and 55, 43, and 0 percent for men in their 50s, 60s, and 70s, respectively [3]. Men who undergo nerve-sparing surgery, and who had a previously high level of sexual functioning are less likely to become impotent after radical prostatectomy. In men who do experience impotence after their surgery, sildenafil (Viagra) may be effective.
Radiation therapy — Two forms of radiation therapy are used to treat prostate cancer: external beam radiation and interstitial implantation, also called brachytherapy.
External beam radiation therapy (EBRT) uses a machine called a linear accelerator that moves around the patient, directing radiation at the pelvis. EBRT is typically administered daily, five days per week. The treatment interval varies between four and seven weeks depending upon whether or not it is used alone, or in combination with brachytherapy (see below). It does not require inpatient hospitalization, and men can usually maintain their normal activities during treatment. The level or dose of radiation that is delivered to the prostate tumor is important, and is determined in part by the pretreatment factors discussed above.
It is difficult to compare outcomes from EBRT with those of radical prostatectomy among similar groups of men who have received these two different treatments for the following reasons:
As noted above, young, healthy men are typically encouraged to undergo surgery, while older patients tend to be steered toward radiotherapy.
During prostatectomy, the pelvic lymph nodes and the tissues surrounding the prostate gland can be directly evaluated for evidence of cancer spread, but this is not possible in men undergoing radiation therapy. As a result, men receiving radiation may actually have more extensive disease than expected from the pretreatment evaluation, compared to those undergoing surgery.
Nevertheless, some generalizations can be made. For men with low-risk, organ-confined prostate cancer, surgery and EBRT result in approximately equivalent rates of cancer control at five years: 80 and 81 percent, respectively [4]. In contrast, men with high risk organ-confined tumors (eg, high serum PSA and high Gleason score) may do better with surgery. In the same report, 62 percent of patients were cancer-free at five years, compared to only 26 percent after radiation [4]. It should be noted that these patients were treated with relatively low doses of EBRT, and at least one study suggests that higher doses of radiation therapy preferentially benefit men with high risk disease [5]. Furthermore, other reports have shown that long-term treatment results from surgery and radiation therapy are similar in men with either low risk or high risk disease when higher doses of radiation are used (72 Gray or higher) [6].
Complications — Although the radiation therapist attempts to limit the amount of radiation that strikes healthy tissue, this is difficult, and some noncancerous tissues may be damaged. The likelihood of damage to tissues around the prostate gland may be less when treatment planning techniques such as conformal radiation therapy, are utilized (see below).
Side effects of EBRT can include urinary urgency and/or frequency, bladder pain, bowel problems, sexual impotence, and proctitis (inflammation of the rectum). Compared to prostatectomy, urinary problems and sexual impotence are less common following radiation therapy, but bowel problems such as diarrhea, bowel urgency, and painful hemorrhoids are more common. In contrast to surgically treated men, impotence often becomes more common with the passage of time after radiation.
These important differences in treatment-related complications continue to be evident two years after treatment. As an example, in a series of 1591 men aged 55 to 74, who were enrolled on the Prostate Cancer Outcomes Study and followed for two years, men undergoing prostatectomy had a more than two-fold higher risk of urinary incontinence compared to those treated with external beam radiation therapy (9.6 versus 3.5 percent) and were more likely to be impotent (80 versus 62 percent) [7]. On the other hand, men receiving radiation therapy reported greater declines in bowel function (diarrhea, bowel urgency, and painful hemorrhoids). Viagra may also be beneficial in men with radiation-related impotence.
3-D CRT radiation therapy — Three-dimensional conformal radiation therapy, or 3-D CRT, uses sophisticated computer modeling to precisely outline the tumor and deliver larger doses of external beam radiation while minimizing damage to surrounding normal tissues. This technique is more expensive than EBRT, and has not yet been proven to be more effective. However, it may allow a higher dose to be administered to the prostate, and produce fewer side effects, particularly bowel problems and sexual impotence. 3-D CRT is still under evaluation as a treatment alternative for early prostate cancer.
Intensity modulated radiation therapy — Intensity modulated radiation therapy (IMRT) is an advanced form of 3D-CRT in which the radiation dose to the prostate gland, a complex and irregular target, is varied by changing the intensity of the beam during therapy. The major advantage of IMRT over 3D-CRT is a reduction in the dose received by adjacent organs, particularly the bowel, resulting in fewer side effects. This form of therapy requires special expertise and equipment, and is not available at all institutions or radiation facilities.
Brachytherapy — Brachytherapy, also called radioactive seed implantation or interstitial therapy, involves placing rice-sized radioactive pellets directly into the prostate gland under ultrasound guidance. These pellets emit radiation from within the gland for a specified period of time before eventually dissipating. Incomplete or incorrect placement of the radioactive seeds can result in incomplete dosage to parts of the prostate, and an inferior outcome.
The advantage of brachytherapy compared with EBRT is primarily convenience; brachytherapy requires a one-time insertion as an outpatient. Radiation exposure to physicians, nursing personnel, and family members is negligible.
There are no studies that directly compare brachytherapy to either radical prostatectomy or EBRT for men with early stage prostate cancer. Brachytherapy appears to be equivalent to other treatments for men with low risk disease, but may be associated with an inferior outcome in men with either higher Gleason grade or higher PSA levels (ie, intermediate or high risk disease) [8].
Complications — Men who undergo brachytherapy may experience acute inflammation and swelling of the prostate gland, which can lead to retention of urine. Thus, men with large or enlarged prostate glands are not good candidates for this treatment. In addition, damage to nearby tissue can cause bowel urgency and frequency, rectal bleeding, and the development of rectal ulcers; these symptoms tend to improve over time.
The risk of urinary incontinence and sexual impotence may be less with brachytherapy than with EBRT, but health-related quality of life is similar following brachytherapy, EBRT, and surgery [9].
A rare complication of prostate brachytherapy is migration of the seeds to the lung. This usually does not cause symptoms, and the clinical significance is unclear.
Watchful waiting — Some men elect to forego active treatment in favor of a program of observation, also called watchful waiting. One reason that men with early prostate cancer might choose watchful waiting over active treatment is to avoid the side effects that commonly occur with the various treatments. However, prostate cancer itself can cause urinary incontinence, sexual impotence, and obstruction to the flow of urine as the tumor grows and the cancer progresses.
Older reports suggested that men with prostate cancer who underwent watchful waiting had similar survival to other men of similar age who did not have prostate cancer. However, a large study from Sweden that directly compared surgery to watchful waiting showed that men undergoing watchful waiting were twice as likely to die of their prostate cancer as compared to those receiving surgery (10 versus 5 percent), despite having similar overall survival (that is, from all causes of death not limited to prostate cancer ) [10]. The fact that twice as many men undergoing watchful waiting developed metastatic disease from prostate cancer at eight years after being enrolled in the study (27 versus 13 percent) suggests that a survival benefit from surgery may become evident as these men are followed for a longer duration of time.
Furthermore, despite the fact that many men who forego treatment do not die of prostate cancer, even those with low grade cancer are at risk to develop incurable bone metastases. In a pooled analysis of 828 men with early stage prostate cancer from six published studies, the likelihood of surviving the prostate cancer at ten years in men with Gleason 2 to 4, or Gleason 5 to 7 tumors was 87 percent, only 34 percent for those with Gleason 8 to 10 tumors [11]. Despite these favorable survival results, one-fifth of men with Gleason 2 to 4 tumors, and almost one-half of those with Gleason 5 to 7 tumors had developed bone metastases by ten years.
Watchful waiting is most appropriate for men over age 70 who have small tumors, low Gleason scores, and a slowly rising PSA level, particularly if they have another medical condition that might limit their life expectancy to less than 15 years. Younger men, and men over the age of 70 who are otherwise healthy and who have aggressive (eg, Gleason score 7) or large tumors should be encouraged to undergo radical prostatectomy or radiation therapy. Such men have more rapid tumor growth, and are more likely to die of their prostate cancer if disease is left untreated.
Men who choose a program of watchful waiting should undergo periodic disease monitoring, with a digital rectal examination and a blood test to determine PSA level every three to six months. A repeat prostate biopsy should be done at some point after the initial diagnosis to make certain that a more aggressive tumor (ie, with a higher Gleason grade) has not become evident. Definitive therapy (ie, radiation or surgery) should be pursued if there is a significant change in either the PSA level, the rectal examination, or Gleason grade on follow-up biopsy.
The estimated survival time for men who forego treatment for early prostate cancer varies according to tumor characteristics. In data from the Connecticut Tumor Registry, which contains 10- to 20-year follow-up information for more than 700 men, men with low risk disease (Gleason score 2 to 4) had only a 4 to 7 percent risk of dying of prostate cancer within 15 years [12]. On the other end of the spectrum, men with Gleason scores of 7 to 10 had a 42 to 87 percent chance of dying of prostate cancer within 15 years. Survival time for men with intermediate scores of 5 or 6 was between the two extremes.
Hormone therapy — Hormone treatment can decrease the body's levels of testosterone and other male hormones, which leads to a decrease in the size of the prostate cancer. In men with early prostate cancer, hormone therapy is often given in conjunction with EBRT, with several studies showing an improvement in local tumor control for a longer period of time when this approach is compared to EBRT alone. Patients undergoing brachytherapy and 3-D CRT seem to have the same benefit from hormone therapy.
The benefit of hormone therapy in conjunction with surgery is less clear. Although several studies have shown a decrease in tumor size and a decrease in the serum PSA concentration when hormone treatment was given prior to radical prostatectomy, none has shown a decrease in relapse rates or improvement in survival with this approach. Thus, it is not considered standard therapy.
Complications — Side effects of hormone therapy are due to the decrease in levels of male hormones; they include decreased libido (sex drive), impotence, and other symptoms similar to those of menopause, such as hot flashes and temporary enlargement of the breast tissue. Hormone therapy can also lead to wasting of muscle and bone, the latter resulting in osteoporosis (thinning of the bones) and an increased risk of bone fractures.
Cryotherapy — Cryotherapy or cryosurgery involves freezing and killing the prostate tumor cells by injecting liquid nitrogen directly into the tumor. The tumor is usually frozen, allowed to thaw, and frozen again, to increase the effectiveness of the treatment. Unlike EBRT, with which patients cannot be retreated, cryotherapy can be repeated if the cancer recurs.
Although this technique is becoming more widely applied, it cannot be recommended with the same sense of confidence as radical prostatectomy or radiation therapy because long-term data are not yet available. Preliminary reports suggest that the same men who benefit from either radical prostatectomy or radiation therapy may also benefit from cryotherapy. However, in at least one report of 975 men undergoing cryosurgery for organ confined disease, only 60 percent of the low-risk patients (T1-T2a, pretreatment serum PSA <10 ng/mL, and Gleason score <7) were free of disease recurrence (as determined by a very low serum PSA level) at five years [13].
Side effects of cryosurgery can include urinary incontinence, sexual impotence, prostatitis (an inflammation of the prostate), and damage to local tissues. About one-half of men treated with this option experience at least one significant side effect. Research into the safety and effectiveness of cryosurgery continues.
SUMMARY OF TREATMENT — For men with early stage prostate cancer, current practice suggests that surgery and radiation therapy produce similar outcomes except for men with aggressive tumors, who may do better with surgery. The "cost" of better tumor control with surgery is a higher frequency of urinary and sexual side effects. Watchful waiting is considered appropriate only for older men with a small tumors, a low Gleason score, and a life expectancy of 15 years or less.
Often, the decision between radiation and surgery is a matter of patient preference. Younger men may be better served by surgery because they are more likely to survive beyond ten years. Older men may prefer radiation therapy to avoid the risks associated with anesthesia and the recovery period associated with major surgery. Although brachytherapy offers some advantages over external beam radiotherapy, there is not enough long-term follow-up data to recommend this approach as a first option, especially in younger men with long life expectancies. A randomized trial directly comparing brachytherapy to prostatectomy will begin enrollment in the United States and Canada in late 2002; is called the SPIRIT trial, and is sponsored by the American College of Surgeons Oncology Group.
Followup with your personal physician is essential.
This answer is not intended as and does not substitute for medical advice - the information presented is for patient education only. Please see your personal physician for further evaluation of your individual case.
Thanks,
Kevin, M.D.
Bibliography:
Klein. Patient information - Treatment for early prostate cancer. UptoDate, 2004.
Patient information: Treatment for early prostate cancer
Eric A Klein, MD
Cleveland Clinic Foundation and Taussig Cancer Center
Prostate cancer is a malignancy of the prostate gland, an organ that forms a ring around the urethra (the tube that carries urine from the bladder to the outside of the body) near its connection to the bladder. Prostate cancer is the most common cancer affecting men. Every year, approximately 189,000 men are diagnosed with prostate cancer in the United States, and 30,200 die from this disease. Over the last decade, the increasing use of prostate cancer screening by measurement of blood levels of prostate-specific antigen (PSA) has led to more cases being diagnosed at an early stage, when the cancer is still restricted to the prostate gland, and highly curable.
There are three standard approaches to treating early prostate cancer: surgical removal of the prostate gland, radiation therapy with or without hormone therapy, and "watchful waiting," a term that describes the decision to delay definitive treatment while carefully monitoring the patient for evidence of progression or growth of the cancer. Hormone therapy has traditionally been reserved for men with advanced or metastatic prostate cancer, although new applications of hormonal therapy as a supplement to watchful waiting, surgery, or radiation show some promise.
The ultimate choice of treatment is dependent upon several factors.
The likelihood that the prostate cancer is confined to the prostate gland and therefore, potentially curable
A man's age and overall health, including any other medical conditions
The outcomes and potential side effects associated with the different forms of treatment
Here we will discuss the pretreatment evaluation of men with early prostate cancer, and describe the available treatment options, outcomes from therapy, and treatment-related side effects.
PRETREATMENT EVALUATION — Prior to selecting the best treatment option, it is critically important that the extent of the prostate cancer be correctly determined. Although the true local extent of involvement can only be determined by surgical removal, several pretreatment factors can be used to predict whether a prostate cancer is likely to be confined to the prostate gland itself (termed organ-confined disease) or spread beyond the prostate gland, and therefore, more advanced. The most important pretreatment factors that determine outcome are the clinical stage, the level of the serum PSA, and the degree of aggressiveness of the tumor, referred to as the Gleason grade.
Prostate cancer stage — Physicians use a common notation to describe the extent, or stage of a cancer. The tumor-node-metastasis (TNM) system is the most common method used to stage prostate cancer (show table 1). Within the TNM system, T1 tumors are microscopic, and cannot be felt by the physician on rectal examination; T2 tumors can be felt with a rectal examination, but appear to be confined to the prostate gland; T3 tumors have grown beyond the prostate into the capsule of connective tissue that surrounds the gland, or into the seminal vesicles (glands near the prostate that secrete fluid into the reproductive tract); T4 tumors have grown locally beyond the prostate, and involve nearby tissues. The finding of a T3 or T4 tumor suggests a more advanced tumor that is not likely to be cured, even with aggressive surgery. It should be noted that the stage that is assigned by a rectal examination is termed a clinical or "c" stage, while a man who has undergone surgical removal of the prostate with microscopic evaluation will be assigned a pathologic, or "p" stage.
Endorectal coil MRI — A new x-ray method called endorectal coil MRI uses magnetic resonance imaging to assess the prostate and its surrounding tissues. Although this technique is not yet widely available, it appears to be particularly helpful in evaluating the possibility of extension outside of the prostate capsule or into the seminal vesicles in men who are considering surgery.
Serum PSA level — The vast majority of men with prostate cancer have elevated levels of PSA in the blood. The level of PSA at the time a prostate cancer is diagnosed provides important information as to the likelihood of finding organ-confined disease. As PSA levels increase, the likelihood of disease spread to tissues beyond the prostate gland rises. Men with a PSA concentration less than 10 ng/mL have a 70 to 80 percent chance of having organ-confined disease, compared to 50 percent for those with PSA levels 10 to 50 ng/L, and only 25 percent with higher PSA levels [1]. Because of this, men with PSA levels above 10 ng/mL are usually recommended to undergo a CT scan of the abdomen and pelvis, and a bone scan prior to treatment in order to detect any spread of tumor to the pelvic and abdominal lymph nodes, or bones.
The pretreatment PSA level can also predict the likelihood of a cancer recurrence after treatment. Men with a lower PSA concentration are more likely to be cancer-free five years after treatment than those with a higher pretreatment PSA level.
Biopsy grade — A prostate biopsy, in which a small amount of tissue is removed from the prostate and examined under a microscope, is typically performed when prostate cancer is suspected. this examination allows the physician to confirm the diagnosis, and also assess the level of aggressiveness (the Gleason grade) of the tumor.
The pathologist typically reports a primary grade (between 1 to 5) and a secondary grade, also between 1 and 5. The higher the Gleason grade, the more aggressive (fast-growing) the tumor appears. These two numbers are then combined together to form the Gleason score. If the cancerous tissue shows primarily grade 3 and secondarily grade 4 areas of tumor involvement, the combined Gleason score is "3 plus 4" or 7. Gleason score 2 to 4 tumors are typically referred to as low grade (also called well-differentiated), Gleason 8 to 10 tumors are high grade (or poorly differentiated), and the Gleason scores between 5 to 7 are referred to as intermediate grade.
Predictive models — These pretreatment factors, and combinations of these factors can be used by physicians in two ways: they are useful to predict the likelihood that a man has an organ-confined cancer that may be potentially curable, and they can also be used to predict the outcome of either surgery or radiation therapy.
Predicting organ-confined cancer — The use of combinations of these pretreatment factors is more accurate than any one of the individual factors to predict the likelihood of a man having organ-confined disease. One such predictive model combines the clinical tumor (T) stage, the Gleason score from the tumor biopsy, and the serum PSA to construct tables that allow an estimation of the likelihood of finding organ-confined, and thus, potentially curable disease at the time of surgery (show table 2).
Predicting treatment outcome — In addition to predicting the likelihood of organ-confined disease, pretreatment models utilizing PSA, biopsy Gleason score, and clinical T stage can also be used to predict the chance of being cancer-free following either surgery or radiation. In general, these models stratify patients into one of three defined prognostic groups:
Low risk — Clinical stage T1c or T2a, serum PSA concentration <10 ng/mL, and biopsy Gleason score 6 or less. Men with low risk disease have a greater than 85 percent chance of being cancer-free five years after treatment with either surgery or radiation therapy.
Intermediate risk — Clinical stage T2b, serum PSA 10 to 20 ng/mL, and a biopsy Gleason score of 7. Men with intermediate risk disease have approximately a 50 percent chance of being cancer-free at five years after treatment.
High risk — Clinical stage T2c disease, serum PSA >20 ng/mL, and a biopsy Gleason score of 8 or higher. High risk patients have an approximately 33 percent chance of being cancer-free five years after treatment.
TREATMENT OPTIONS FOR EARLY PROSTATE CANCER — The three standard therapies for men with organ-confined prostate cancer are surgery (radical prostatectomy), radiation therapy, and watchful waiting. To date, no good study has directly compared these three options. Young, healthy men are typically encouraged to undergo radical prostatectomy, while older patients tend to be steered toward radiotherapy or observation. This fact makes it difficult to compare outcomes in men treated with either surgery or radiation.
Radical prostatectomy — Radical prostatectomy entails a complete removal of the prostate gland. This treatment option is thought to offer the best chance for long-term survival (beyond ten years). Men with low-risk early stage prostate cancer who undergo radical prostatectomy have an 80 to 85 percent chance of remaining cancer-free up to 15 years after surgery.
During a radical prostatectomy, the surgeon removes the entire prostate and then reconnects the urethra and bladder. The prostate gland may be removed from two different approaches: the perineal approach, or the retropubic approach. One advantage of the retropubic approach is that it allows tissue to be removed from the lymph nodes within the pelvis prior to surgical removal of the prostate. This lymph tissue is then evaluated for evidence of tumor spread (termed nodal metastases); the prostate gland is removed only if the lymph nodes are free of cancer.
Complications — Serious or life-threatening complications from radical prostatectomy are rare. The most common complications are urinary incontinence (uncontrolled leakage of urine) and sexual impotence (the inability to have an erection sufficient for sexual intercourse). Advances in technique in recent years have reduced the incidence of both these conditions by sparing the nerves responsible for urinary and sexual function, although a nerve-sparing prostatectomy is not possible in all men. Nerve-sparing surgery is not usually recommended for men who have large tumors, high Gleason grade cancers, or a high PSA before treatment. For other men with prostate cancer, there is no evidence that a nerve-sparing operation compromises control of the cancer.
The majority of men are incontinent and impotent immediately following surgery. However, both tend to improve with time after surgery. Age is an important factor in the risk of urinary incontinence after prostatectomy. In a large study that monitored over 1,200 men for two years after surgery, extreme urinary incontinence was experienced by almost 14 percent of men between 75 and 79, but in fewer than 4 percent of younger men [2]. Almost one-half of the affected men had only occasional urinary incontinence, often related to stresses on the bladder such as sneezing, coughing, or laughing.
The likelihood of experiencing sexual impotence after radical prostatectomy also increases with age. In one review, the potency rate after surgery was 100 percent for men in their 40s, and 55, 43, and 0 percent for men in their 50s, 60s, and 70s, respectively [3]. Men who undergo nerve-sparing surgery, and who had a previously high level of sexual functioning are less likely to become impotent after radical prostatectomy. In men who do experience impotence after their surgery, sildenafil (Viagra) may be effective.
Radiation therapy — Two forms of radiation therapy are used to treat prostate cancer: external beam radiation and interstitial implantation, also called brachytherapy.
External beam radiation therapy (EBRT) uses a machine called a linear accelerator that moves around the patient, directing radiation at the pelvis. EBRT is typically administered daily, five days per week. The treatment interval varies between four and seven weeks depending upon whether or not it is used alone, or in combination with brachytherapy (see below). It does not require inpatient hospitalization, and men can usually maintain their normal activities during treatment. The level or dose of radiation that is delivered to the prostate tumor is important, and is determined in part by the pretreatment factors discussed above.
It is difficult to compare outcomes from EBRT with those of radical prostatectomy among similar groups of men who have received these two different treatments for the following reasons:
As noted above, young, healthy men are typically encouraged to undergo surgery, while older patients tend to be steered toward radiotherapy.
During prostatectomy, the pelvic lymph nodes and the tissues surrounding the prostate gland can be directly evaluated for evidence of cancer spread, but this is not possible in men undergoing radiation therapy. As a result, men receiving radiation may actually have more extensive disease than expected from the pretreatment evaluation, compared to those undergoing surgery.
Nevertheless, some generalizations can be made. For men with low-risk, organ-confined prostate cancer, surgery and EBRT result in approximately equivalent rates of cancer control at five years: 80 and 81 percent, respectively [4]. In contrast, men with high risk organ-confined tumors (eg, high serum PSA and high Gleason score) may do better with surgery. In the same report, 62 percent of patients were cancer-free at five years, compared to only 26 percent after radiation [4]. It should be noted that these patients were treated with relatively low doses of EBRT, and at least one study suggests that higher doses of radiation therapy preferentially benefit men with high risk disease [5]. Furthermore, other reports have shown that long-term treatment results from surgery and radiation therapy are similar in men with either low risk or high risk disease when higher doses of radiation are used (72 Gray or higher) [6].
Complications — Although the radiation therapist attempts to limit the amount of radiation that strikes healthy tissue, this is difficult, and some noncancerous tissues may be damaged. The likelihood of damage to tissues around the prostate gland may be less when treatment planning techniques such as conformal radiation therapy, are utilized (see below).
Side effects of EBRT can include urinary urgency and/or frequency, bladder pain, bowel problems, sexual impotence, and proctitis (inflammation of the rectum). Compared to prostatectomy, urinary problems and sexual impotence are less common following radiation therapy, but bowel problems such as diarrhea, bowel urgency, and painful hemorrhoids are more common. In contrast to surgically treated men, impotence often becomes more common with the passage of time after radiation.
These important differences in treatment-related complications continue to be evident two years after treatment. As an example, in a series of 1591 men aged 55 to 74, who were enrolled on the Prostate Cancer Outcomes Study and followed for two years, men undergoing prostatectomy had a more than two-fold higher risk of urinary incontinence compared to those treated with external beam radiation therapy (9.6 versus 3.5 percent) and were more likely to be impotent (80 versus 62 percent) [7]. On the other hand, men receiving radiation therapy reported greater declines in bowel function (diarrhea, bowel urgency, and painful hemorrhoids). Viagra may also be beneficial in men with radiation-related impotence.
3-D CRT radiation therapy — Three-dimensional conformal radiation therapy, or 3-D CRT, uses sophisticated computer modeling to precisely outline the tumor and deliver larger doses of external beam radiation while minimizing damage to surrounding normal tissues. This technique is more expensive than EBRT, and has not yet been proven to be more effective. However, it may allow a higher dose to be administered to the prostate, and produce fewer side effects, particularly bowel problems and sexual impotence. 3-D CRT is still under evaluation as a treatment alternative for early prostate cancer.
Intensity modulated radiation therapy — Intensity modulated radiation therapy (IMRT) is an advanced form of 3D-CRT in which the radiation dose to the prostate gland, a complex and irregular target, is varied by changing the intensity of the beam during therapy. The major advantage of IMRT over 3D-CRT is a reduction in the dose received by adjacent organs, particularly the bowel, resulting in fewer side effects. This form of therapy requires special expertise and equipment, and is not available at all institutions or radiation facilities.
Brachytherapy — Brachytherapy, also called radioactive seed implantation or interstitial therapy, involves placing rice-sized radioactive pellets directly into the prostate gland under ultrasound guidance. These pellets emit radiation from within the gland for a specified period of time before eventually dissipating. Incomplete or incorrect placement of the radioactive seeds can result in incomplete dosage to parts of the prostate, and an inferior outcome.
The advantage of brachytherapy compared with EBRT is primarily convenience; brachytherapy requires a one-time insertion as an outpatient. Radiation exposure to physicians, nursing personnel, and family members is negligible.
There are no studies that directly compare brachytherapy to either radical prostatectomy or EBRT for men with early stage prostate cancer. Brachytherapy appears to be equivalent to other treatments for men with low risk disease, but may be associated with an inferior outcome in men with either higher Gleason grade or higher PSA levels (ie, intermediate or high risk disease) [8].
Complications — Men who undergo brachytherapy may experience acute inflammation and swelling of the prostate gland, which can lead to retention of urine. Thus, men with large or enlarged prostate glands are not good candidates for this treatment. In addition, damage to nearby tissue can cause bowel urgency and frequency, rectal bleeding, and the development of rectal ulcers; these symptoms tend to improve over time.
The risk of urinary incontinence and sexual impotence may be less with brachytherapy than with EBRT, but health-related quality of life is similar following brachytherapy, EBRT, and surgery [9].
A rare complication of prostate brachytherapy is migration of the seeds to the lung. This usually does not cause symptoms, and the clinical significance is unclear.
Watchful waiting — Some men elect to forego active treatment in favor of a program of observation, also called watchful waiting. One reason that men with early prostate cancer might choose watchful waiting over active treatment is to avoid the side effects that commonly occur with the various treatments. However, prostate cancer itself can cause urinary incontinence, sexual impotence, and obstruction to the flow of urine as the tumor grows and the cancer progresses.
Older reports suggested that men with prostate cancer who underwent watchful waiting had similar survival to other men of similar age who did not have prostate cancer. However, a large study from Sweden that directly compared surgery to watchful waiting showed that men undergoing watchful waiting were twice as likely to die of their prostate cancer as compared to those receiving surgery (10 versus 5 percent), despite having similar overall survival (that is, from all causes of death not limited to prostate cancer ) [10]. The fact that twice as many men undergoing watchful waiting developed metastatic disease from prostate cancer at eight years after being enrolled in the study (27 versus 13 percent) suggests that a survival benefit from surgery may become evident as these men are followed for a longer duration of time.
Furthermore, despite the fact that many men who forego treatment do not die of prostate cancer, even those with low grade cancer are at risk to develop incurable bone metastases. In a pooled analysis of 828 men with early stage prostate cancer from six published studies, the likelihood of surviving the prostate cancer at ten years in men with Gleason 2 to 4, or Gleason 5 to 7 tumors was 87 percent, only 34 percent for those with Gleason 8 to 10 tumors [11]. Despite these favorable survival results, one-fifth of men with Gleason 2 to 4 tumors, and almost one-half of those with Gleason 5 to 7 tumors had developed bone metastases by ten years.
Watchful waiting is most appropriate for men over age 70 who have small tumors, low Gleason scores, and a slowly rising PSA level, particularly if they have another medical condition that might limit their life expectancy to less than 15 years. Younger men, and men over the age of 70 who are otherwise healthy and who have aggressive (eg, Gleason score 7) or large tumors should be encouraged to undergo radical prostatectomy or radiation therapy. Such men have more rapid tumor growth, and are more likely to die of their prostate cancer if disease is left untreated.
Men who choose a program of watchful waiting should undergo periodic disease monitoring, with a digital rectal examination and a blood test to determine PSA level every three to six months. A repeat prostate biopsy should be done at some point after the initial diagnosis to make certain that a more aggressive tumor (ie, with a higher Gleason grade) has not become evident. Definitive therapy (ie, radiation or surgery) should be pursued if there is a significant change in either the PSA level, the rectal examination, or Gleason grade on follow-up biopsy.
The estimated survival time for men who forego treatment for early prostate cancer varies according to tumor characteristics. In data from the Connecticut Tumor Registry, which contains 10- to 20-year follow-up information for more than 700 men, men with low risk disease (Gleason score 2 to 4) had only a 4 to 7 percent risk of dying of prostate cancer within 15 years [12]. On the other end of the spectrum, men with Gleason scores of 7 to 10 had a 42 to 87 percent chance of dying of prostate cancer within 15 years. Survival time for men with intermediate scores of 5 or 6 was between the two extremes.
Hormone therapy — Hormone treatment can decrease the body's levels of testosterone and other male hormones, which leads to a decrease in the size of the prostate cancer. In men with early prostate cancer, hormone therapy is often given in conjunction with EBRT, with several studies showing an improvement in local tumor control for a longer period of time when this approach is compared to EBRT alone. Patients undergoing brachytherapy and 3-D CRT seem to have the same benefit from hormone therapy.
The benefit of hormone therapy in conjunction with surgery is less clear. Although several studies have shown a decrease in tumor size and a decrease in the serum PSA concentration when hormone treatment was given prior to radical prostatectomy, none has shown a decrease in relapse rates or improvement in survival with this approach. Thus, it is not considered standard therapy.
Complications — Side effects of hormone therapy are due to the decrease in levels of male hormones; they include decreased libido (sex drive), impotence, and other symptoms similar to those of menopause, such as hot flashes and temporary enlargement of the breast tissue. Hormone therapy can also lead to wasting of muscle and bone, the latter resulting in osteoporosis (thinning of the bones) and an increased risk of bone fractures.
Cryotherapy — Cryotherapy or cryosurgery involves freezing and killing the prostate tumor cells by injecting liquid nitrogen directly into the tumor. The tumor is usually frozen, allowed to thaw, and frozen again, to increase the effectiveness of the treatment. Unlike EBRT, with which patients cannot be retreated, cryotherapy can be repeated if the cancer recurs.
Although this technique is becoming more widely applied, it cannot be recommended with the same sense of confidence as radical prostatectomy or radiation therapy because long-term data are not yet available. Preliminary reports suggest that the same men who benefit from either radical prostatectomy or radiation therapy may also benefit from cryotherapy. However, in at least one report of 975 men undergoing cryosurgery for organ confined disease, only 60 percent of the low-risk patients (T1-T2a, pretreatment serum PSA <10 ng/mL, and Gleason score <7) were free of disease recurrence (as determined by a very low serum PSA level) at five years [13].
Side effects of cryosurgery can include urinary incontinence, sexual impotence, prostatitis (an inflammation of the prostate), and damage to local tissues. About one-half of men treated with this option experience at least one significant side effect. Research into the safety and effectiveness of cryosurgery continues.
SUMMARY OF TREATMENT — For men with early stage prostate cancer, current practice suggests that surgery and radiation therapy produce similar outcomes except for men with aggressive tumors, who may do better with surgery. The "cost" of better tumor control with surgery is a higher frequency of urinary and sexual side effects. Watchful waiting is considered appropriate only for older men with a small tumors, a low Gleason score, and a life expectancy of 15 years or less.
Often, the decision between radiation and surgery is a matter of patient preference. Younger men may be better served by surgery because they are more likely to survive beyond ten years. Older men may prefer radiation therapy to avoid the risks associated with anesthesia and the recovery period associated with major surgery. Although brachytherapy offers some advantages over external beam radiotherapy, there is not enough long-term follow-up data to recommend this approach as a first option, especially in younger men with long life expectancies. A randomized trial directly comparing brachytherapy to prostatectomy will begin enrollment in the United States and Canada in late 2002; is called the SPIRIT trial, and is sponsored by the American College of Surgeons Oncology Group.
Followup with your personal physician is essential.
This answer is not intended as and does not substitute for medical advice - the information presented is for patient education only. Please see your personal physician for further evaluation of your individual case.
Thanks,
Kevin, M.D.
Bibliography:
Klein. Patient information - Treatment for early prostate cancer. UptoDate, 2004.
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by maxster63, Jan 17, 2004 12:00AM
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