About a quarter of a million men will be diagnosed with prostate cancer each year. Unlike most cancers which have a peak age of incidence,the incidence of prostate cancer increases with age so that between 60 and 79 years of age it is about 1 in 8. However, when a family member has the disease,the relative risk is further increased. Because of the aging of the American male and the decrease in cardiovascular deaths from improved treatment,it is likely that a rise will be seen in prostate cancer. However,because of the broad spectrum of biological activity of prostate cancer,disease management may be difficult to individualize.
Prevention and Etiology
Testosterone profoundly affects the development of prostate cancer. Prostate cancer does not occur in eunuchs. There is an increased incidence of prostate cancer amongst relatives of patients with prostate cancer and in Afro-American men. A high-fat diet may also predispose towards prostate cancer. Along with a high fat diet,inflammatory cells within the prostate may lead to cells which may be precursors of prostatic intraepithelial neoplasia(PIN) and prostatic carcinoma.
Men who are at risk as outlined above,men over 55,men who have difficulty with urination,men with an enlarged prostate or men with an elevated prostatic specific antigen(PSA) blood test but have a negative prostate biopsy may benefit from daily proscar/avodart. These drugs are 5 alpha reductase inhibitors and block the conversion of testosterone to dihydrotestosterone.
Daily proscar/avodart can result in a reduction in the size of the prostate,decreased volume of ejaculate and a decrease in the PSA (but this reduction does not necessarily mean less of a chance of having prostate cancer). These medications have a low incidence of side effects that may include low libido or desire for intercourse,erectile dysfunction or breast enlargement. Statins may produce similar side effects without lowering the serum testosterone.
Most men with early prostate cancer have no symptoms. Minor voiding symptoms may be related to associated benign enlargement of the prostate than the early prostate cancer. More locally advanced prostate cancer may cause significant voiding symptoms or urinary retention and or obstruction of the ureters and renal failure. Prostate cancer that has spread to the bones may cause pain or fracture of the vertebrae with spinal cord compression and paralysis.
For early prostate cancer there are usually no signs. However,induration or a prostate nodule may be detected on a digital rectal examination(DRE)
For early prostate cancer,usually the only abnormal finding will be an abnormal %free PSA (prostatic specific antigen) and or total PSA blood test. More advanced cases may show elevations of BUN and Cr,alk phos. and acid phos. blood levels.
Prostatic Specific Antigen( PSA) is a serine protease produced by the prostatic epithelium and periurethral glands in the male. This substance is secreted in the seminal fluid and is partly responsible for the liquefaction of the coagulated semen.
a) % free PSA
Of the various forms in which the PSA can be measured,the % free PSA appears more sensitive in picking up early prostate cancer. PSA exists in both bound (to protein) and unbound states. Men with prostate cancer have a greater proportion of serum PSA that is bound resulting in a lower % free PSA. A % free PSA of 25 or above suggests a low likelihood of prostate cancer. However, we have found the % free PSA to be valuable in detecting early prostate cancer,especially when the total PSA (the most common form of PSA measurement) is between 1.6 and 4.0 and the % free is less than 20. Therefore you should ask your physician to measure your % free PSA.
b) total PSA
The normal total PSA is 4.0 ng/ml or less but does not hold a lot of accuracy. It can be deceptively normal and miss an early prostate cancer. Also, the total PSA can be normal and elevated in men with a large prostate,if there is chronic prostatitis (often asymptomatic),after a urinary infection,ejaculation,prostate massage,prostatic infarct and after a prostate biopsy.
This is a highly sensitive third generation PSA assay that can be used to detect very early disease progression especially for intermediate and high risk patients.
Spurious lab results are also not uncommon and an abnormal blood level is worth repeating to verif y the level.
c) PSA velocity
Measures the rate at which a PSA rises. A PSA rising more than 0.75ng/ml per year may be significant.
d) PSA density
This is calculated by determining the figure of total PSA over prostatic volume.
The PCA3 is a gene that exists in the nuclear material of epithelial cells from the prostate and that maybe shed into the urine. The gene is a noncoding segment of mRNA located on chromosome 9 and is over expressed by prostate cancer cells.The PSA,however, is a glycoprotein that can enter the bloodstream.
The PCA3 urinary test begins with careful examination /massage of the prostate. The first voided urine after this examination is then collected and submitted to the laboratory for analysis. The result is expressed as a score,a ratio of PCA3 to PSAmRNA. A normal score is considered to be 35×10 to the minus 3 or less. This test maybe useful in men who have elevations of PSA and a negative biopsy or in those that have had a microfocus of prostate cancer on one biopsy and then a follow up negative biopsy.
Since the % free PSA is more sensitive in picking up early prostate cancer,screening for prostate cancer should be undertaken using this blood test rather than the inaccurate total PSA. Early detection is important since not all prostate cancers are slow growing,even in the elderly.
For prostate screening,the blood test is combined with the digital rectal examination of the prostate. The digital exam may have some usefulness in determining the approximate size of the prostate,it’s texture ( a hard nodule may suggest cancer) and whether there is tenderness to touch.
Prostate Biopsy (TRUS/BX)
This is done through a transrectal ultrasound guided needle biopsy of the prostate. In our practice we have patients stop anti coagulants for at least 5 days and start the antibiotics cipro and flagyl at least one day before,the day of and for three days after the biopsy. He also takes an enema 2 hours before the procedure. The patient is placed on his side and the ultrasound probe introduced into the rectum. Local anesthetic is injected about the prostate as a peri prostatic nerve block and then a number of sextant needle biopsies taken. Trying to infer cancerous areas on the basis of the ultrasound gray scale images is inaccurate and the only value of these images is to determine the size of the prostate,whether there are calcifications and or cysts and to know that the biopsy needle is in the area of the prostate that requires sampling.
There is no evidence for any prostatic cancer seeding from the needle biopsy as the tissue is extracted through the hollow core of the biopsy needle.
Saturation Sextant Biopsies. Most prostate biopsies performed in the office under a peri-prostatic nerve block are routinely taken from six (sextant) areas of the prostate,base of the prostate.middle of the prostate and apical regions of the prostate,right and left sides that give you the six areas of tissue sampling. This sampling is usually sufficient. However, we will have men undergo a saturation biopsy under outpatient sedation where we will sample greater than 20 cores of prostate tissue,especially when a man has had a previous pathology report indicating a microfocus of prostate cancer or unilateral prostatic involvement with cancer and we wish to verify the presence of prostate cancer or be sure that it is indeed only in one side of the prostate.
Ensuring that it is only involving one side of the prostate is important for those men considering treatment only to the involved area (focal) or involved half (unilateral) of the prostate so that they can be sure to preserve their potency.
3D mapping with a brachytherapy grid for extended saturation biopsy of the prostate is done by some with view to more precise targeted focal ablation of the prostate cancer but is not routine.
Most prostate cancers (over 95%) are adenocarcinomas. The remainder are transitional,small cell (or neuro endocrine and may possibly occur in response to prolonged androgen deprivation) or sarcomas.Basically, the non-adenocarcinomas may be grouped into either epithelial or non-epithelial. PIN and atypical small acinar proliferation(ASAP) are believed to be precursor lesions to prostate cancer.
The prostate is divided into four distinct glandular zones,peripheral,central,periprostatic and transitional. About a third of the bulk of the prostate,however, is made up of the anterior fibromuscular stroma which is devoid of glands and not one of the zones.
About 70% of prostate cancers originate in the peripheral zone of the prostate and about 20% in the transitional zone and 10% in the central zone of the prostate.
This is a grading of the histological patterns of the prostate cancer seen under the microscope and then given a score.
The score is used to determine the aggressiveness of the adenocarcinoma (the most common type of prostate cancer).
As there are usually more than one histological pattern seen under the microscope,the two most prevelant are graded,primary and secondary,and the Gleason score is a combination of the two grades or patterns. Each pattern is given a grade between 1 to 5 with 1 being the least aggressive and 5 the most. The grades of the two most common patterns are combined for a Gleason score. A Gleason score of 7 or above indicates a more aggressive cancer and a poorer prognosis.
Reviewing your prostate needle biopsy report
After your systematic sextant transrectal needle biopsy of the prostate a number of needle core samples are taken and evaluated histologically under the microscope by the pathologist. Usually between 12 and 20 representative sextant core samples are taken from the prostate.
a) the sextant location is given ie right or left,base, mid zone or apex ( a minimum of 2 needle biopsies from each sextant should be taken)
b) the length of the needle core sample is given and a standard length biopsy core is about 15mm
c) the needle gauge used for the biopsy is usually about 18g or 20g with the 18g taking a larger diameter sample. An 18g prostate needle biopsy specimen represents only about 0.03% of the prostate gland tissue.
e) each needle core is analyzed for tumor and the length of tumor involvement measured and recorded as length and as a percentage of that needle biopsy.
A core length of 3mm or more in one or two needle biopsy specimens can predict a prostate cancer of clinically significant volume (0.5cc or greater). Also, a small amount of tumor is not equivalent to a low grade tumor or a small amount of prostate cancer necessarily.
f. microscopy, stains and ploidy
in order to examine the needle biopsy samples of the prostate each of the preserved specimens undergoes a 2 micron cut and placed on a slide and stained with H+E (hematoxylin and eosin) and examined with the microscope using low and high power. Most labs also utilize a triple immunohistochemistry stain to improve cancer detection.
The immunohistochemistry stain consists of 3 antibodies:
a. racemase (P504s) Staining of this protein is seen in prostate cancer and hi grade PIN but not benign prostatic tissue.
b. high molecular weight cytokeratin (34b-E12). Stains the cytoplasm of basal cells of the prostate. Cancer cells fail to react with this antibody.
c. p63 antibody. Stains the nucleus of basal cells.
Patients with diploid prostate cancer cells (normal DNA content in their prostate cancer cells) have longer cancer free intervals and survival and their cancers are more responsive to hormonal therapy than those with non diploid content.
g) the Gleason grade (discussed above) for each needle biopsy specimen is recorded. A Gleason score of 7 or greater indicates a more aggressive lesion.
h) associated findings
i) prostatic intraepithelial neoplasia (PIN)
ii) atypical small cell acinar proliferation (ASAP)
These are both thought to be precursor lesions for prostate cancer and men found to have these on their biopsy report may warrant repeat biopsies at some future time.
iii) atypia. Here there may be some abnormal cellular morphology but not consistent with malignancy.
iv) perineural invasion. The prognostic significance of perineural invasion by prostate cancer is debatable.
If your biopsy report indicates a MICROFOCUS of prostate cancer (assuming enough biopsies of appropriate core length were taken) then we would not act on such a biopsy but have you undergo a saturation biopsy,possibly under sedation to verify whether the existence of prostate cancer can be confirmed. It has been our experience that we cannot always confirm the existence of prostate cancer after previously finding one microfocus amount amongst all the specimens taken . Therefore, we will not direct a man to undergo prostate cancer treatment based on the presence one microfocus of prostate cancer in the report. A PCa3 test may be useful corroborating data also.Close follow up with PCa3’s and further biopsies are of course warranted.
The use of ultrasound to image the prostate via a transrectal approach can come in various forms.
ii) color doppler sonography
iii) contrast enhanced sonography
iv) ultrasound based realtime elastography
v) microbubble ultrasound
Here ultrasound involves the use of color doppler imaging with microbubble contrast. The microbubbles are tiny bubbles of gas and since blood flow is more prevalent in cancerous tissue,the microbubbles tend to concentrate here and then identify the cancerous lesion.
With this technique, computer assisted ultrasonography is used which is capable of acquiring and transferring volumetric radiofrequency data.
Imaging is undertaken to ensure that the prostate cancer is indeed localized to the prostate so that the treatment selected will be appropriate for optimizing cure. Imaging is usually not necessary when the PSA is 10 or less. However, aggressive prostate cancers (those with a Gleason score of 7 or greater) may produce less PSA than expected and imaging may still be appropriate here although the PSA may be 10 or less.
b) CT/MRI Scans
MRI scans are also used to localize cancerous lesions within the prostate and also to determine possible localized spread. MRI but especially functional multimodality MR imaging includes high resolution MR imaging,dynamic contrast enhanced MR imaging,MR spectroscopy (MRS) and diffusion weighted MR imaging. With this functional multimodality MR imaging it is possible to detect and localize the prostatic cancer lesion with a high degree of accuracy. In this way it is feasible to perform image guided focal therapy.
c) Bone scan
Patients with a PSA of 15 or greater are at risk for bone spread and should be considered for a bone scan to determine whether there has been spread from the prostate.
d) Endo rectal magnetic resonance imaging
This involves the use of a specialized coil inserted into the rectum and may improve imaging of the prostate and prostate cancer and determine whether the cancer has spread beyond the confines of the prostate.
Use of magnetic resonance spectroscopy in conjunction with the MRI may improve the imaging accuracy of prostate cancer even further.
e) Prostascint scan
An antibody to a prostate specific antigen is conjugated to inidium but the scans usefulness has been limited by too many false positives and negatives.
f) PET scan
Positron emission tomography (PET) when combined with a computer tomography (CT) scan and the use of the imaging agent choline,is able to detect recurrent prostate cancer earlier than conventional methods can.
This is an attempt to determine through the studies already mentioned as to whether the prostate cancer is localized, spread locally or spread to more distant sites. The staging system for prostate cancer used currently is the T(tumor)N(nodes)M(metastasis) system. This system uses the results of the imaging, DRE and the TRUS (trans rectal ultrasound) but not the results of the needle biopsy.
Tis carcinoma in situ (PIN)
T1a <5% in BPH resection has PCa,normal DRE
T1b >5% in BPH resection has PCA,normal DRE
T1c detected by elevated PSA,normal DRE
T2a tumor palpable by DRE,visible on TRUS one side
T2b tumor palpable by DRE visible by TRUS both sides
The T1c and T2a and T2b lesions are the ones that are typically picked up on prostate screening
T3 outside prostate capsule or into seminal vesicle
T3a extracapsular extension on one or both sides
T3b seminal vesicle involvement
T4 locally advanced beyond the prostate
Tumor extends into bladder neck,sphincter or rectum
N0 no regional node involvement
N1 regional node involvement
M0 no metastatic spread
M1 metastatic spread
M1a metastasis in non regional lymph nodes
M1b metastasis to bone
M1c distant metastasis to other sites
Reviewing your Risk Assessment (D’Amico risk stratification for prostate cancer)
The following criteria may be used to formulate your risk group when considering treatment options with curative intent.
1. Low Risk
Gleason< or equal to 6. If 50% of the biopsies contain cancer,your risk increases.
Because this group may have a recurrence rate of less than 20%,these men may be suitable candidates for minimally invasive treatment options for their prostate cancer.
2. Intermediate Risk
Gleason 7. If 50% of your biopsies contain cancer,your risk increase
Some men in this group may also be candidates for minimally invasive treatment options.
3. High Risk
Biochemical Free Survival (BFS)
BFS usually parallels the criteria for cure.
The PSA nadir is the lowest level PSA that is achieved after any treatment for prostate cancer. Ideally that should be 0.2ng/ml or lower and is a good indicator of cure.
There are several definitions of biochemical failure:
i). ASTRO (American Society of Radiation Oncologists) which defines failure as 3 consecutive rises in PSA above the post treatment PSA nadir.
ii). Phoenix,nadir+2.0ng/ml PSA rise.
iii). Stuttgart,nadir+1.2ng/ml PSA rise and specifically designed to evaluate HIFU.
Concerns for treatment failure may then be evaluated with a prostate biopsy to determine whether there is residual cancer.
Treatment of Localized Prostate Cancer
Treatment of prostate cancer is based on Gleason grade,stage of disease and life expectancy of the patient and a degree of surgeons preference for one of the treatment options for localized prostate cancer discussed below. These can be broadly categorized as minimally invasive (HIFU (acoustic surgery),Cryoablation and others such as RITA),radiation options,surgical options and surveillance. Definitive and curative treatment options are usually reserved for those with a life expectancy of greater than 10 years.
a) minimally invasive
These treatment options for prostate cancer have become increasingly attractive due to there success,low complication rate and the fact that they are performed as an outpatient under an anesthetic and are radiation free.
Furthermore there has been an increasing move towards unilateral and focal treatment of prostate cancers,particularly in younger men who seek greater assurance that their erectile function will not be compromised. We routinely suggest these options,especially in those men where a repeat saturation TRUS/BX (transrectal ultrasound and needle biopsy of the prostate) has confirmed unilateral or focal disease. Focal Therapy Focal Therapy may include all the approaches in which there is less than total prostate ablation and can be a suitable option for the man with prostate cancer in the low risk category. Particularly if it is a small volume prostate cancer of 0.5cc or less. This may be from a). lesion directed to b).hemi prostate ablation to the so called c). “hockey stick” with hemi ablation and partial treatment of the opposite side but with nerve sparing on this side. Currently, the techniques that can offer these minimally invasive focal treatment options are,cryoablation (cryotherapy),high intensity focused ultrasound (HIFU)and MRI guided transperineal laser ablation. The concern with offering focal therapy is of course, is the prostate cancer lesion truely focal? Unifocal prostate cancers are much more common in white males but their incidence is probably less than 30%. Also,prostate cancers located in the anterior portion of the prostate may not be sampled as readily on a needle biopsy and also may have a worse prognosis than lesions located in other parts of the prostate. Furthermore, as most most of the focal treatment lesions produced by the various techniques are more or less spherical in shape, prostate cancer lesions may not be spherical.
Also of great importance is the fact that men who have been previously treated with surgery or radiation and then on follow up found to have recurrent disease can have additional definitive treatment of their prostate cancer recurrence with one of the minimally invasive options.
1. HIGH INTENSITY FOCUSED ULTRASOUND (HiFu) – For more information on HIFU, please visit our dedicated site at HIFUrx.com
High Intensity Focused Ultrasound (HIFU) is a treatment that uses ultrasound wave energy focused on the prostate via a transrectal probe. Multiple focal areas of destruction are created within the prostate. The prostate tissue is destroyed through coagulation by the ultrasound wave energy causing rapid heat elevation to about 90 degrees at the focal point. A Japanese study has shown that in men who had a PSA of 10 or less there was a localized disease free rate of 94% three years after HIFU. Candidates for the HIFU treatment are those that have localized disease or men who have recurrence after previous radiation or cryo ablation of their prostate cancer. After the diagnosis of prostate cancer and the appropriate imaging and laboratory studies have been done in an attempt to establish that the cancer is contained just to the prostate, measurement of prostate size is important.
Ideally we like to have the prostate size at 40g or less otherwise the procedure can be unduly lengthy. Prostates that are greater than 40g can be downsized with lupron and avodart. Noting the presence of calcification within the prostate is also important as these may disperse the ultrasound waves to compromise the treatment. A TURP may be necessary to remove these areas of calcification and or also downsize the prostate. Before the HIFU procedure,the patient is given 1 or 2 enemas till the effluent is clear. The HIFU procedure is then done under a spinal or general anesthetic in the lithotomy position and can take 1 to 4 hours depending upon the size of the prostate. At the end of the procedure a foley catheter is placed (sometimes a supra pubic cather is placed at the start of the procedure) to drain the bladder. This catheter may need to be in place for 1 to 2 weeks before prostate swelling from the treatment settles and spontaneous voiding can resume. After the treatment the patient may spend 1 to 2 hours in the recovery room and then instructed on catheter care and his post operative course of medicines. These medications usually include antibiotics,an anti inflammatory,flomax and cialis.
Once the foley catheter has been removed,the patient may notice some temporary difficulty with urination,frequency,burning as well as some mild urgency. He may also notice the passge of small amounts of tissue and some blood. This will all resolve.
Unlike the other treatment options of surgery,radiation and cryo ablation,the more severe complications of incontinence,impotence,urethral stricture and rectal fistula are relatively uncommon. Furthermore, while all the treatment options may result in incomplete eradication of the cancer within the prostate,HIFU can easily be repeated. Postoperatively and once normal urination has returned,the patient will be checked with a PSA every 3 months for the first year after treatment.
Download the HIFU brochure on the right for more information
Click here for the spanish version
Cryoablation of the prostate may be used to treat localized prostate cancer or recurrences after previous radiation treatment. Cryoablation of the prostate may be done either through total freezing of the prostate or through focal or regional freezing to treat only the involved section of the prostate. In this manner the nerves for erection sitting on the uninvolved part of the prostate may remain intact to preserve erections.
The surgery is done by inserting 6-8 slender probes transperineally into the prostate under transrectal ultrasound control. Argon gas is circulated through the probes to freeze the prostate while helium is used to warm it. Two freeze thaw cycles are usually performed in the treatment process.
Several temperature sensors carefully monitor the process to determine that target freezing temperatures are reached while adjacent areas such as the sphincter and rectum are protected. A warming catheter protects the urethra from very cold temperatures.
This surgery is usually performed as an outpatient and commonly you will have a foley catheter draining your bladder for about a week. The cryoablation procedure can also be performed focally in that only the involved lobe of the prostate is treated and therefore minimizing the risk of impotence. This outpatient cryoablation procedure can also be repeated if the prostate cancer should recur.
3. MRI guided transperineal focal laser prostate cancer ablation
Here, using a combination of MRI and transrectal ultrasound imaging,a laser fiber is guided transperineally into the prostate after the prostate cancer is identified and focal laser treatment performed. This can be done as an outpatient.
RITA or radio frequency interstitial tumor ablation is undergoing additional evaluation in the treatment of prostate cancer. This procedure may be performed as an outpatient in an office setting under sedation. Radio frequency energy is applied via needles placed transperineally into the prostate under transrectal ultrasound guidance and with rectal temperature monitoring.
PROSTATE CANCER SURGERY? Lies, lies and more damned lies.
Bert Vorstman, MD,MS,FAAP,FRACS,FACS
“Choosing prostate cancer surgery was the worst decision of my life” patient
There is no creditable scientific evidence for significant curative life extension in men treated for prostate cancer through radical prostate surgery/robotics alone. In addition, this one surgery is associated with more permanent complications than probably any other operation ever, performed on humans. It’s an operation that is often treated as an emergency, is without merit and is probably without equal in providing false hope. Unbelievably, this high-risk surgical technology for prostate cancer treatment was simply given a pass by the FDA without being rigorously and scientifically evaluated for risk or reward.
Read The Full PDF Report on “Prostate Cancer Surgery”
b) Radical Prostatectomy
This can be undertaken conventionally by a retropubic approach,perineally or laparoscopically and aided by robotics.
Morbidity associated with all types of radical prostatectomy is significant from immediate intra operative complications which may include blood loss and rectal and ureteral injury. Post operative complications include wound infection,DVT(deep vein thrombosis),PE (pulmonary embolus), pelvic lymphocele,urinary leakage through the anastomosis and foley catheter dislodgement. Late complications with impotence and incontinence are common although there may be some improvement of the incontinence with time. Failing resolution of the incontinence with time,additional surgical options involving endoscopic collagen injections periurethrally, urethral slings and artificial sphincters may be offered. Impotence may also improve with time but may be enhanced through early use of PDE-5 inhibitors with or without the aid of the vacuum device.
Post operative scarring or stricturing of the anastomosis or join between the urethra and bladder neck may also occur and require incision which may again lead to incontinence. Some men will also note some shrinking of their penis after radical prostatectomy.
Of most concern however after this treatment option for prostate cancer is the incidence of positive margins or cancer cells left behind. This occurs in 20 to 40% of men who have undergone radical prostatectomy which then necessitates the need for additional treatment such as radiation.
c) Radiation Therapy
i) External beam radiation is more commonly undertaken now through either 3 dimensional conformal radiation or intensity modulated radiation therapy or proton therapy as they may be able to target the prostate better and possibly preserve better the surrounding tissues from the effects of the radiation. Conformational external beam radiation therapy uses 3-D images of the prostate and surrounding organs to aim precisely (conform) the radiation to the prostate and attempt to spare adjacent organs.
3-D Conformational Radiation
3-D conformational radiation and intensity modulated radiation therapy (IMRT) can allow greater radiation doses to the tumor with greater accuracy.
Image guided radiation therapy uses 3 small gold markers placed on the boundary of the prostate percutaneously before treatment allowing appropriate radiation alignment.
Cyberknife is a robotic radiosurgery system which delivers high dose radiation to the prostate (without cutting) with extreme accuracy and therefore minimizing radiation damage to adjacent tissues. For the prostate,a treatment dose can be delivered in 5 days. This is a much shorter delivery time than for other forms of external beam radiation to the prostate.
Proton Beam Therapy
Proton beam therapy uses protons to treat prostate cancer but may have no advantage over other radiation options and is far more costly. The radiation usually takes place over several weeks.
Radiation to the pelvic nodes in addition to the prostate may be useful in treating microscopic spread of prostate cancer to the pelvic lymph nodes if present.
Radioactive implants(iodine 125 or palladium103) are permanently implanted into the prostate (interstitial implant) through a TRUS guided transperineal needle as an outpatient under a general anesthetic. Temporary implants are not routinely performed.
Many men will undergo combined external beam radiation and brachytherapy with or without ADT.
Side effects of radiation may be early or late. Early on men may experience irritative voiding or rectal symptoms with frequency and urgency. Late side effects may include erectile dysfunction (ED) which may be worsened by the ADT if administered. Other late complications may include radiation induced hemorrhagic cystitis or proctitis. At times these complications can be severe requiring additional intervention,blood transfusions and possibly hyperbaric oxygenation. Men having undergone brachytherapy may also experience urinary retention and or a urethral stricture requiring further surgery.
Concurrent treatment with androgen deprivation therapy (ADT) such as lupron for somewhere between 3 to 24 months may be useful in improving outcomes.
This option (treatment withheld,possibly temporarily,possibly permanently) may be adopted in men with prostate cancer according to the following situations:
i) men where only one microfocus of prostate cancer was detected amongst many cores. He will need rigorous follow up with serial DRE’s,PSA’s and TRUS/BX’s. In some men we have been unable to confirm the existence of prostate cancer on subsequent studies when they have previously had a biopsy which had shown a microfocus.
ii) in older men with low risk prostate cancer disease or those men that do not have a greater than 10 year life expectancy.
Treatment of Metastatic Prostate Cancer
Most prostate cancers are relatively hormone-sensitive, and treatment is designed to employ some pathway to the control of testosterone production.
A. Androgen Deprivation Therapy (ADT)
This is an important subject in prostate cancer control as prostate cancer thrives on testosterone and is arrested when testosterone is blocked or deprived.
ADT can be achieved surgically as in orchiectomy (removal of the testicles) or medically and this may be short term,permanent or intermittent in administration.
As a consequence of ADT serum testosterone is lowered by 95% (95% of testosterone comes from testicles and 5% from adrenals). As well, as serum estrogen is lowered by 80% in men. This results in an estrogen deficiency state in men also. Selective estrogen modulators (SERM’s) are being investigated for their placement in the treatment protocol.
Agents for ADT
1. LHRH agonists like Lupron/Zoladex reduce LH causing the testicles to stop testosterone (but also estrogen) production.
2. Antiandrogen agents such as Casodex/Eulexin block access of testosterone to androgen receptors inside the cancer cell.
3. 5 alpha reductase inhibitors such as Avodart/Proscar block conversion of testosterone to dihydrotestosterone.
ADT may be permanent for men with advanced stages of prostate cancer or may be temporary when used in men with high risk disease after definitive treatment with surgery or after radiation.
Temporary ADT is also used to downsize large volume prostates prior to one of the minimally invasive treatment options or before radiation.
In this instance ADT is not used to control metastatic spread but either to shrink the size of the prostate or, as an adjunctive treatment for several months after the treatment of high risk disease with either surgery or radiation.
Side Effects of ADT
ADT has both benefits in treating and arresting the growth and spread of prostate cancer and in shrinking the size of the prostate, as well as having some downsides. Therefore, the use of these agents needs to be tempered with these issues in mind.
1. Cardiovascular. ADT can bring about changes in the lipid profile and men with pre existing coronary artery disease are at greater risk of a cardiac incident. The risk is more apparent after a few months of ADT and if use is considered beyond a few months,cardiac screening may be reasonable.
2. Bone loss. ADT can bring about bone loss in the form of osteopenia and osteoporosis and therefore a greater risk of fractures such as vertebral. After 10 years of ADT about 80% of men will have osteoporosis and 5-8% will have a clinically apparent fracture. Fractures help to decrease the survival rate in these men.
These side effects can be ameliorated with calcium and vitamin D supplements or Actonel/Fosomax.
3. Hot flashes and gynecomastia (breast enlargement). The hot flashes are due to decreased estradiol and increased catecholamine release and vasodilation and can be treated with Megace or Effexor.
4. Penile atrophy and erectile dysfunction. This may respond to medications such as Cialis/Levitra or Viagra with or without the vacuum device for so called penile rehab.
5. Emotional. May respond to medications such as Zoloft
6. Anemia. May resond to medications such as Epogen
7. Joint pains. May require anti inflammatory medications or Celebrex
Chemotherapy is generally reserved for those men whose metastatic prostate cancer is showing resistance to hormonal treatment,otherwise known as hormone refractory prostate cancer.
Several agents such as 5-Fluorouracil, docetaxel, Adriamycin, estramustine phosphate, cyclophosphamide and hydroxyurea have produced some marginal responses. There has been a resurgence in use of combined regimens, which may act synergistically and may achieve higher response rates.
C. Immunotherapy and Immune Enhancement
Tumor antigens (as in metastatic prostate cancer) are used for T cell mediated attack and dendritic cells are a key element in this T cell activation.
Strontium 89 is a pure beta radiation emitting compound, and when given systemically travels to metastatic bone involvement where there are areas of new bone activity. This agent may bring about significant relief of pain.
Chemo Prevention of Prostate Cancer
Recent studies have suggested about a 5% reduction in the detection of prostate cancer in those men taking one 5mg pill of finasteride daily. However,in those men taking the finasteride that did develop a prostate cancer,about 5% of these men had a more aggressive Gleason grade than expected. Additional studies are pending.
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