The New York Times, September 20, 2011, By TARA PARKER-POPE

Treatments for prostate cancer take a significant toll on male potency, leaving a surprisingly high percentage of men unable to have a normal sex life, new research shows.

The findings, based on a study of more than 1,000 men treated for prostate cancer at multiple medical centers, show that whether a man is able to achieve adequate erections after treatment for prostate cancer varies greatly depending on a number of individual variables, including his age, the extent of his cancer and the quality of his sex life before treatment.

Over all, fewer than half of the men who reported good sexual function before cancer had managed to regain it two years after treatment. But the chances of sexual recovery varied widely. After two years, some men had less than a 10 percent chance of achieving adequate erections after treatment, whereas others had a 70 percent or greater chance of a relatively normal sex life.

The results were not encouraging, but for the first time offer men a more personalized model for predicting sexual recovery after cancer treatment.

Cancer experts say the data, published Tuesday in The Journal of the American Medical Association, are sorely needed, in light of marketing efforts that are aimed at wooing men toward particular types of treatment but that often leave patients with unrealistic expectations. Many men report feeling shocked and depressed when their sex lives fail to return to normal after treatment.

“I think being transparent about what the pros and cons are, the reality — that’s important,’’ said Dr. Martin G. Sanda, senior author on the research and co-director of the prostate cancer program at the Dana-Farber/Harvard Cancer Center. “For any of the treatments for prostate cancer, it would be misleading to tell someone they have a 100 percent chance of sexual recovery, or even a 95 percent chance. It’s easier for a couple to face that and deal with that if they are expecting it than if they were oversold and told there weren’t going to be any issues.”

The study evaluated sexual function among men at nine academic medical centers who had undergone one of three treatments for prostate cancer: surgical removal of the prostate; radiation therapy; or brachytherapy, which uses radioactive seed implants.

Over all, just 35 percent of men in the surgery group, 37 percent of men in the hormone group and 43 percent of men in the brachytherapy group were able to have sexual intercourse two years after treatment.

Because the men weren’t randomly assigned to a treatment, the data don’t demonstrate whether one treatment is better than another. For instance, men who opt for brachytherapy are typically younger and healthier than men who undergo radiation treatment, so the results can’t be compared.

However, the researchers were able to determine which variables are most important for predicting a man’s erectile function after treatment. In all three treatment groups, the quality of a man’s erections before treatment — determined using a questionnaire about his sex life — helped predict his sexual recovery. Among surgical patients, a man’s age and his P.S.A. score, which measures prostate specific antigen, and whether he had nerve-sparing surgery also helped predict his chances of resuming a normal sex life. For men undergoing radiation treatment, those who had not also undergone hormone therapy were more likely to regain erectile function two years after treatment. Among men who had brachytherapy, a younger age and lower body weight helped predict a better recovery compared with men who were older or obese.

One limit of the study is that it followed the men for only two years. Men who undergo radiation and brachytherapy may experience a decline in erectile function two or more years after treatment, whereas men who undergo surgery may experience improvement.

Dr. Sanda said the data would allow doctors to take a more personalized approach as they talk to patients about the risks of a given treatment and counsel them about the benefits of drugs and other therapies that can improve erectile function.

“By and large, a lot of what we counsel men has been based on generalized average numbers,’’ said Dr. Sanda. “This really creates a more concrete metric as to what patients might expect.”

 

 

 

 

Prostate Cancer Biopsy

 

 

Prostate Cancer Biopsy

If a physical exam or PSA test suggests a problem, your doctor may recommend a biopsy. A needle is inserted either through the rectum wall or the skin between the rectum and scrotum. Multiple small tissue samples are removed and examined under a microscope. A biopsy is the best way to detect cancer and predict whether it is slow-growing or aggressive.

 

 

Side View of the Prostate

 

 

Picture of the Prostate

The prostate is a walnut-sized gland located between the bladder and the penis. The prostate is just in front of the rectum. The urethra runs through the center of the prostate, from the bladder to the penis, letting urine flow out of the body.

The prostate secretes fluid that nourishes and protects sperm. During ejaculation, the prostate squeezes this fluid into the urethra, and it’s expelled with sperm as semen.

The vasa deferentia (singular: vas deferens) bring sperm from the testes to the seminal vesicles. The seminal vesicles contribute fluid to semen during ejaculation.

 

 

Treatments and Drugs

 

By the Mayo Clinic Staff

Your prostate cancer treatment options depend on several factors, such as how fast your cancer is growing, how much it has spread, your overall health, as well as the benefits and the potential side effects of the treatment.

Immediate treatment may not be necessary
For men diagnosed with a very early stage prostate cancer, treatment may not be necessary right away. Some men may never need treatment. Instead, doctors sometimes recommend watchful waiting, which is sometimes called active surveillance. In watchful waiting, regular follow-up blood tests, rectal exams and possibly biopsies may be performed to monitor progression of your cancer.

If tests show your cancer is progressing, you may opt for a prostate cancer treatment such as surgery or radiation. Watchful waiting may be an option for cancer that isn’t causing symptoms, is expected to grow very slowly and is confined to a small area of the prostate. Watchful waiting may also be considered for a man who has another serious health condition or an advanced age that makes cancer treatment more difficult. Watchful waiting carries a risk that the cancer may grow and spread between checkups, making it more difficult to treat.

Radiation therapy
Radiation therapy uses high-powered energy to kill cancer cells. Prostate cancer radiation therapy can be delivered in two ways:

  • Radiation that comes from outside of your body (external beam radiation). During external beam radiation therapy, you lie on a table while a machine moves around your body, directing high-powered energy beams, such as X-rays, to your prostate cancer. You typically undergo external beam radiation treatments five days a week for several weeks.
  • Radiation placed inside your body (brachytherapy). Brachytherapy involves placing many rice-sized radioactive seeds in your prostate tissue. The radioactive seeds deliver a low dose of radiation over a long period of time. Your doctor implants the radioactive seeds in your prostate using a needle guided by ultrasound images. The implanted seeds eventually stop giving off radiation and don’t need to be removed.

Side effects of radiation therapy can include painful urination, frequent urination and urgent urination, as well as rectal symptoms, such as loose stools or pain when passing stools. Erectile dysfunction can also occur.

Hormone therapy
Hormone therapy is treatment to stop your body from producing the male hormone testosterone. Prostate cancer cells rely on testosterone to help them grow. Cutting off the supply of hormones may cause cancer cells to die or to grow more slowly. Hormone therapy options include:

  • Medications that stop your body from producing testosterone. Medications known as luteinizing hormone-releasing hormone (LH-RH) agonists prevent the testicles from receiving messages to make testosterone. Drugs typically used in this type of hormone therapy include leuprolide (Lupron, Eligard,), goserelin (Zoladex), triptorelin (Trelstar), histrelin (Vantas) and degarelix (Firmagon).
  • Medications that block testosterone from reaching cancer cells. Medications known as anti-androgens prevent testosterone from reaching your cancer cells. Examples include bicalutamide (Casodex), flutamide, and nilutamide (Nilandron). These drugs typically are given along with an LH-RH agonist or given before taking an LH-RH agonist.
  • Surgery to remove the testicles (orchiectomy). Removing your testicles reduces testosterone levels in your body. The effectiveness of orchiectomy in lowering testosterone levels is similar to that of hormone therapy medications, but orchiectomy may lower testosterone levels more quickly.

Hormone therapy is used in men with advanced prostate cancer to shrink the cancer and slow the growth of tumors. In men with early-stage prostate cancer, hormone therapy may be used to shrink tumors before radiation therapy. This can make it more likely that radiation therapy will be successful. Hormone therapy is sometimes used after surgery or radiation therapy to slow the growth of any cancer cells left behind.

Side effects of hormone therapy may include erectile dysfunction, hot flashes, loss of muscle and bone mass, reduced sex drive, and weight gain. Hormone therapy also increases the risk of heart disease and heart attack. Doctors believe long-term use of hormone therapy and the low hormone levels that result may lead to cardiovascular problems.

Surgery to remove the prostate
Surgery for prostate cancer involves removing the prostate gland (radical prostatectomy), some surrounding tissue and a few lymph nodes. Ways the radical prostatectomy procedure can be performed include:

  • Making an incision in your abdomen. During retropubic surgery, the prostate gland is taken out through an incision in your lower abdomen. Compared with other types of prostate surgery, retropubic prostate surgery may carry a lower risk of nerve damage, which can lead to problems with bladder control and erections.
  • Making an incision between your anus and scrotum. Perineal surgery involves making an incision between your anus and scrotum in order to access your prostate. The perineal approach to surgery may allow for quicker recovery times, but this technique makes removing the nearby lymph nodes and avoiding nerve damage more difficult.
  • Laparoscopic prostatectomy. During a laparoscopic radical prostatectomy, several small incisions are made in the abdomen. The doctor inserts special surgical tools through the incisions, including a long, slender tube with a small camera on the end (laparoscope). The laparoscope sends images to a monitor in the operating room. The surgeon watches the monitor as he or she guides the instruments. Laparoscopic surgery may offer a shorter hospital stay and quicker recovery than traditional surgery.
  • Using a robot to assist with surgery. During robotic laparoscopic surgery, the instruments are attached to a mechanical device (robot). The surgeon sits at a console and uses hand controls to guide the robot to move the instruments. Using a robot during laparoscopic surgery may allow the surgeon to make more precise movements with surgical tools than is possible with traditional laparoscopic surgery. Discuss with your doctor which type of surgery is best for your specific situation.

Radical prostatectomy carries a risk of urinary incontinence and erectile dysfunction. Ask your doctor to explain the risks you may face based on your situation, the type of procedure you select, your age, your body type and your overall health.

Freezing prostate tissue
Cryosurgery or cryoablation involves freezing tissue to kill cancer cells. During cryosurgery for prostate cancer, small needles are inserted in the prostate using ultrasound images as guidance. A very cold gas is placed in the needles, which causes the surrounding tissue to freeze. A second gas is then placed in the needles to reheat the tissue. The cycles of freezing and thawing kill the cancer cells and some surrounding healthy tissue. Original attempts to use cryosurgery for prostate cancer resulted in unacceptable side effects. Doctors hope newer technologies will make cryosurgery safer.

Heating prostate tissue using ultrasound
High-intensity focused ultrasound treatment uses powerful sound waves to heat prostate tissue, causing cancer cells to die. High-intensity focused ultrasound is done by inserting a small probe in your rectum. The probe focuses ultrasound energy at precise points in your prostate. High-intensity focused ultrasound treatments are being studied in clinical trials. More study is needed to understand the benefits and risks of this treatment.

Chemotherapy
Chemotherapy uses drugs to kill rapidly growing cells, including cancer cells. Chemotherapy can be administered through a vein in your arm, in pill form or both. Chemotherapy may be a treatment option for men with prostate cancer that has spread to distant areas of their bodies. Chemotherapy may also be an option for cancers that don’t respond to hormone therapy. Doctors are studying whether chemotherapy is helpful when combined with radiation therapy or surgery.

 

 

Introduction to Brachytherapy

Medscape.com  —  Brachytherapy (the term is derived from the Greek word brachys, which means brief or short) refers to cancer treatment with ionizing radiation delivered via radioactive material placed a short distance from, or within, the tumor. In prostate cancer, brachytherapy involves the ultrasound- and template-guided insertion of radioactive seeds into the gland.

Along with radical prostatectomy, cryotherapy, and external beam radiation therapy (EBRT; most recently termed intensity-modulated radiation therapy [IMRT]), interstitial brachytherapy is a potentially curative treatment for localized prostate cancer. For appropriately selected patients, brachytherapy appears to offer cancer control comparable to these other techniques. Although proponents of brachytherapy claim better quality-of-life results, the evidence supporting this claim is mixed.

The various institutions that offer brachytherapy have subtle differences in technique. Most of the techniques discussed in this article are generic, but some modifications are unique to the implant procedure performed at the University of Virginia.

History of the procedure

In the 1970s, several centers used brachytherapy to treat prostate cancer. Implants were placed into the prostate under direct vision following open pelvic lymphadenectomy. Unfortunately, long-term follow-up revealed less-than-satisfactory results in terms of cancer control.

Currently, these less-than-optimal results are thought to have resulted from 2 problems. The first was a technical inability to accurately implant the sources. The second was the relative paucity of objective dosimetric criteria by which to analyze the radiation dose in that era. Interest in brachytherapy waned in the early 1980s because of these results, the advent of more advanced EBRT equipment, and the development of the nerve-sparing radical prostatectomy.

In the late 1980s and early 1990s, the emergence of transrectal ultrasonography (TRUS) and the development of template guidance led to the introduction of percutaneous brachytherapy for the treatment of localized prostate cancer. This technique was supported by improved dosimetry and offered the potential advantage of delivering a higher radiation dose to the prostate than would be possible with EBRT. This latter consideration was particularly important in view of the high rate of positive prostate biopsy findings following conventional EBRT.

Indications

Evidence-based protocols for brachytherapy have been developed, although data are limited. A 2008 research summary by the Agency for Healthcare Research and Quality (AHRQ) noted that no randomized controlled trials had compared brachytherapy alone with other major treatment options for clinically localized prostate cancer.[1]

The American Brachytherapy Society (ABS) formed a committee of experts in prostate brachytherapy to develop consensus guidelines through a critical analysis of published data supplemented by the experts’ clinical experience.[2] The recommendations of the panel were reviewed and approved by the board of directors of the ABS. They published a review of their recommendations concerning permanent (low-dose rate) implants in 2007.

Patients with a high probability of organ-confined disease are appropriately treated with brachytherapy alone. Most practitioners include patients with stage T1-T2a (according to the American Joint Committee on Cancer/International Union Against Cancer 1997 staging), PSA level of 10 ng/mL or less, and Gleason score of 6 or lower in this category. The recommended prescription doses for monotherapy are 145 Gy for iodine (I)–125 and 120-125 Gy for palladium (Pd)–103.

Brachytherapy candidates with a significant risk of extraprostatic extension should be treated with supplemental IMRT. A high risk of extraprostatic extension is defined as the presence of 2 or more of the following risk factors:

  • Gleason score ≥ 7
  • Prostate-specific antigen (PSA) level > 10 ng/mL
  • Stage higher than T2b

The IMRT dose is 40-50 Gy with a boost of 110 Gy or 100 Gy, depending on which IMRT dose was administered.

Intermediate-risk patients have only one of the aforementioned risk factors. Brachytherapy monotherapy appears to demonstrate good results in several studies. The combination of IMRT and brachytherapy has not uniformly produced better cancer-control results. Length of follow-up time is critical for discerning treatment differences.

A patterns-of-care study conducted by Frank et al found that a subset of intermediate-risk patients are treated with brachytherapy monotherapy.[3] Specifically, monotherapy is used to treat T1c disease characterized by absent perineural invasion, positive results in less than 30% of core samples, and a Gleason score of 7 or a PSA level of 10-20 ng/mL. Even select T2a and T2b cases were treated with monotherapy.

A current Radiation Therapy Oncology Group (RTOG) trial, RTOG 0232, is assessing the role of IMRT plus brachytherapy boost versus brachytherapy alone in the treatment of intermediate-risk prostate cancer in a prospective randomized setting. Until results of this study are available, individual radiation oncologists typically assess risk across the wide range included within the intermediate-risk category to base treatment recommendations.

Salvage brachytherapy

Recurrent disease and residual disease after therapy are fairly common in patients with prostate cancer, with rates ranging from 25-85% depending on initial therapy and disease type. The National Cancer Institute’s Physician Data Query (ie, PDQ – NCI’s Comprehensive Cancer Database, formerly known as CancerNet) reports that approximately 10% of patients initially treated with radiation experience relapse. Local recurrence presents a difficult challenge because the therapeutic options are limited.

Over the past few years, salvage brachytherapy has been increasingly advocated as a therapeutic option in addition to salvage prostatectomy. A 2003 series by Koutrouvelis et al reported success with salvage brachytherapy after prior brachytherapy, but note that this success was reported in only one study with 31 patients[4] ; therefore, such a treatment plan must be considered with caution. The table below summarizes some of the pertinent literature pertaining to these newer modalities.

Table 1. Salvage Brachytherapy (Open Table in a new window)

Authors and

Years

No. of Patients

Isotope (Dose)

Disease-Free Survival

Median Follow-Up (Range)

Koutrouvelis et al, 2003[4] 31 Pd-103 in 26, I-125 in 5 87% (biochemical control) 30 mo
Beyer, 1999[5] 17 I-125 (120 Gy) in 15, Pd-103 (90 Gy) in 2 53% (5-y PSA progression by ASTRO* criteria) 54 mo (23-147 mo)
Grado et al, 1999[6] 49 I-125 or Pd-103 34% (5-y PSA progression by 2 successive rising PSA values above posttreatment PSA nadir) 64 mo
*American Society for Therapeutic Radiology and Oncology

Data on salvage brachytherapy are very immature. Larger studies and longer follow-up are needed before a definitive conclusion on the efficacy of this modality is established.

Contraindications to Brachytherapy

Relative contraindications to brachytherapy include the following:

  • Prior transurethral resection of the prostate
  • Pubic arch interference
  • Obstructive symptoms
  • Morbid obesity
  • Transurethral resection of the prostate

Initially, prior transurethral resection of the prostate was associated with increased symptoms and urinary incontinence rates as high as 50%. More recent studies have reported incontinence rates of less than 10%.

Pubic arch interference

Interference may occur because of a large prostate (a gland >40 g), and this interference may preclude adequate placement of seeds. Hormonal ablation, exaggerated lithotomy, horizontal probe position, and CT-guided placement are all potential solutions.

Obstructive symptoms

Significant preoperative obstructive symptoms increase the likelihood of postoperative urinary retention. While patients with glands larger than 40 g are more likely to have obstructive symptoms, symptoms can occur in anyone.

Glands between 50 and 60 g require downsizing. Hormone ablation has been reported to downsize the prostate gland by 25-40% and is used to facilitate brachytherapy in patients with large glands. However, in one randomized study of patients with prostates of comparable size who underwent brachytherapy alone or brachytherapy after hormone ablation, acute urinary retention and dysuria were actually greater in the hormone ablation group.[7]

Clinicians often compromise and use a 5-alpha reductase inhibitor rather than true androgen ablation for downsizing. Nonetheless, brachytherapy is not advisable in patients with glands larger than 60 g.

Morbid obesity

In morbidly obese patients, the equipment often cannot sustain the patient’s weight or is not long enough to reach the prostate.

High-Dose-Rate Brachytherapy

In addition to permanent brachytherapy, temporary brachytherapy has also been used. In this technique, the implants deliver radiation to the prostate at a higher dose rate than is provided by a permanent implant. Currently, the most common isotope used for temporary brachytherapy is iridium (Ir)–192, which provides a higher dose of radiation than the iodine-125 and palladium-103 permanent implants.

For high-dose-rate brachytherapy, a preplan is devised using transrectal ultrasonography (TRUS) to deliver 15 Gy to the prostate and smaller doses to the urethra and rectum.

During the implantation, hollow needles are inserted transperineally and checked via TRUS to ensure reproduction of the preplan template. The needles are then connected to an automated remote-controlled loading machine. This device successively moves Ir-192 wires into the needles to the dwell positions for various durations. The total irradiation time is usually only 5-10 minutes.

High-dose-rate brachytherapy is commonly delivered in 2 or more fractions of 810 Gy or more, with 6-24 hours between treatments. Patients require hospitalization while the implants remain in place but may go home once the implants are removed.

High-dose-rate brachytherapy is usually used in combination with IMRT. The optimal patient population has not yet been determined. Most series reported are from single centers.

Early experience with high-dose-rate brachytherapy revealed excessive toxicity, and subsequently, adjustments were made to fractionate the dose into 4-7 treatments. Advantages of this approach include a short duration of treatment, minimization of applicator movement, and optimization of dose distribution because sources are mobile. Disadvantages include increased adverse effects and the need for hospitalization.

Most brachytherapy for prostate cancer is performed using the permanent technique, which is the focus of the remainder of this article.

 

 

 

Preparation

 

Anesthesia for Brachytherapy

Epidural, spinal, or general anesthesia may be used for placement of implants.

 

Equipment for Brachytherapy

Currently, the 2 most common permanent radioactive sources for brachytherapy seeds are iodine (I)-125 and palladium (Pd)-103. Of the 2 types, Pd-103 has a higher radiobiologic effect, and thus, its total dosing can be lower. Clinical evidence to guide selection of the radionuclide (Pd-103 or I-125) is lacking. However, because in vitro data have raised some concerns about the efficacy of I-125 in poorly differentiated and rapidly growing tumors, Pd-103 is used more commonly in higher-grade prostate cancers.

A prospective randomized multicenter trial examined long-term morbidity associated with I-125 compared with that of Pd-103 in the treatment of low-risk prostate cancer. The study found that patients who received I-125 were more likely to develop proctitis, while patients who received Pd-103 were more likely to develop prostatitis.[8]

Careful treatment planning should mitigate the adverse effects associated with I-125. A study by Niehaus et al evaluated International Prostate Symptom Scores (IPSSs) in 976 patients treated with brachytherapy and demonstrated that neither isotope was favorable in terms of IPSS resolution, catheter dependence, or need for postbrachytherapy surgical intervention.[9]

Studies of cesium (Cs)–131 in permanent prostate brachytherapy have been increasing. Cs-131 is an attractive alternative, as its average energy is similar to that of I-125 and it has a half-life of only 9.7 days.

Positioning for Brachytherapy

The patient is placed in lithotomy position for brachytherapy (see image below).

 

Brachytherapy for prostate cancer. Lithotomy positioning and graphic representation of how brachytherapy is performed.

Laboratory Studies

Preprocedure laboratory studies include the following:

  • Complete blood count
  • Prothrombin time
  • Activated partial thromboplastin time
  • Metabolic panel
  • Urine culture

Planning and Dosimetry

The amount of radiation to be delivered to the prostate and the configuration of the implants must be assessed prior to placement of the implants. As experience with the technique has broadened, the planning and dosimetry stage has evolved from preplanning days to weeks in advance to intraoperative planning. The ABS has defined the following terminology to clarify the differences in the techniques.

Preplanning is the creation of a plan days or weeks before the implant procedure. Intraoperative planning is treatment planning in the operating room without moving the ultrasound probe.

Intraoperative preplanning is the creation of a plan in the operating room, with immediate execution of the plan. Interactive planning is stepwise refinement of a plan using computerized dose calculations derived from images of needle placement.

Intraoperative treatment planning does not eliminate the need for postimplant dosimetric analysis.

Imaging Studies

In order to perform accurate dosimetry and real-time visualization of percutaneous source placement, the prostate and margins of adjacent organs (eg, rectum, bladder) must be well visualized. Transrectal ultrasonography (TRUS) and CT scanning are the 2 major modalities currently in use.

TRUS has the advantages of real-time imaging and sharp contour of the posterior prostate and rectal wall. Its disadvantage is that its accuracy depends on the operator’s skill. The accuracy of CT scanning, on the other hand, does not depend on the operator’s skill, but prostate margins are less well defined with this imaging modality.

With either modality, initial 5-mm slices are obtained from the base of the bladder to the pelvic floor. A target, which includes the prostate contour, with a generous allotment to the apex and a tighter margin at the base, is developed from these images. The apex tends to allow for less seed migration because of the presence of the pelvic floor muscles here, as opposed to the looser periprostatic tissue at the base.

Traditionally, a portion of the seminal vesicles is included in the target of radiotherapy.

The information on the target volume and margins is then transmitted to a computer program, and the computer helps perform the dosimetry, plan the number of seeds, and define their location on a 2-dimensional grid.

The strategy of seed placement is somewhat controversial. Some experts advocate uniform distribution of seeds while others emphasizing placement on the periphery of the prostate, where most cancers arise.

Preoperative Workup

The preoperative workup includes the following:

  • Bowel preparation, both mechanical and antibiotic
  • Prophylactic intravenous antibiotics at the time of the procedure
  • Subcutaneous heparin if the patient has a history of deep venous thrombosis
  • Stoppage of all anticoagulants, including aspirin, nonsteroidal anti-inflammatory drugs, and warfarin

 

 

 

Overview of Technique

Dosimetric planning of the implant should be performed in all patients before or during seed insertion. Debate persists as to whether intraoperative planning or preplanning is preferred. A modified peripheral loading plan is preferred when the sources are placed.

The dose is the unit of absorbed energy per weight of tissue. For example, the basic unit of radiation, the gray (Gy), is 1 J/kg of tissue.

In brachytherapy, the sharp radiation dose fall-off allows for a high degree of rectal sparing and for a higher total dose to be delivered to the prostate gland itself. Similar advantages can be obtained with conformal intensity-modulated radiation therapy (IMRT), but while brachytherapy has a much lower initial dose rate than IMRT, the aggregate radiation delivery is higher. The average doses are 10 Gy/wk for IMRT and 40 Gy/wk for Pd-103 and 13 Gy/wk for I-125 brachytherapy implants.

A perineal template and transrectal ultrasonographic (TRUS) or computed tomography (CT) are used to guide placement of the needles into the prostate. Once the final needle position is established, the seeds are delivered.

TRUS-Guided Implantation Technique

A biplanar transrectal ultrasonography (TRUS) probe is best at 5, 6, or 7.5 MHz. Attach the probe to the stepping unit, which moves the probe in a cephalad or caudal direction at 0.5-cm intervals.

To differentiate the bladder from the prostate, use a urinary catheter to visualize the urethra or instill diatrizoate (Renografin) in the bladder. Secure the scrotum out of the perineal field with tape or towel clips.

Re-creation of planning images

Match the probe image to the planning image. Adjust the needle-guide template against the perineum, with 1-3 cm of space between the skin and the template. When intraoperative planning is being used, re-creation of the images is not necessary. The benefits of intraoperative planning are that optimal settings are determined in real time and variations are minimized (ie, no re-creation of prior plan). One drawback is that the operative time is longer, but the patient needs to come in only once.

Needle insertion

Needles are inserted through holes in the template, then through skin. Watch for deflection and reposition as needed. Avoid anterior pubic bones. Burnished-tip needles are easier to see when the sonogram becomes distorted by previously placed needles. Avoid piercing the urethra, and ensure that no needle is closer than 0.5 cm to the rectal wall.

Needle depth

Adjust the needle depth based on the preplan zero plane. Use a longitudinal ultrasonographic view. To mark the location of the bladder neck, perform fluoroscopy using a Foley balloon or instill diatrizoate.

Source placement

Afterloading or Mick applicator techniques can be used. Remove the needle slowly to avoid source migration in the afterloading technique. Observe seed positioning under fluoroscopy.

CT-Guided Implantation Technique

A planning CT scan is obtained several days before the procedure, with a urinary catheter in place. The catheter and diatrizoate serve to mark the bladder-prostate border. The prostate is scanned at 5-mm intervals with images that are 5 mm thick.

At the start of the procedure, a urethral catheter is placed that has wire through it and lead markers at 1-cm intervals. The template stand is mounted against the perineum. Most brachytherapists do not use a rectal marker.

Needle placement

Initially, 2 needles are inserted simultaneously just posterior to the urethra on either side of the midline. Then, all anterior needles are inserted to limit prostate mobility. Anterior sources are placed first. Posterior needles are placed again, using 1-cm urethra markers for guidance.

Source placement options

For the Mick applicator, pull the needle back from the zero plane at 5-mm intervals. Use preloaded needles. Rigid Absorbable Permanent Implant Device (RAPID; Amersham Health; Princeton, NJ) Strand seeds (ie, I-125 seeds adsorbed onto a silver rod) are an option. Watch the placement of each source using repeat CT scanning. Perform a final CT scan of the prostate and postimplant dosimetry.

 

 

 

Post-Procedure
Allow the patient to recover from anesthesia. Patients are discharged home the same day. Continue antibiotic prophylaxis, using oral antibiotics, for several days postoperatively. A voiding trial is initiated. If the patient cannot void, a catheter is reinserted and another trial is performed in 5-7 days.

A final CT scan of the prostate and postimplant dosimetry are performed (only in transrectal ultrasonography [TRUS]–guided cases) from 1-30 days following the procedure. If a “cold spot” is observed, reimplantation can be performed.

Many brachytherapists perform cystoscopy to look for sources in the bladder or the urethra. Additional plain radiographs should be obtained to verify the seed count (see the image below).

 

Brachytherapy for prostate cancer. Abdominal radiograph following the procedure.

Until the ideal postoperative interval for CT scanning has been determined, each institution should perform dosimetric evaluation of prostate implants at a consistent postoperative interval. This interval should be reported. Isodose displays should be obtained at 50%, 80%, 90%, 100%, 150%, and 200% of the prescription dose and displayed on multiple cross-sectional images of the prostate.

Dose-volume histography of the prostate should be performed, and all centers should report the D90 (dose to 90% of the prostate gland). Additionally, the following should be reported and ultimately correlated with clinical outcome in the research environment:

  • The D80
  • The D100
  • The fractional V80, V90, V100, V150, and V200 (ie, the percentage of prostate volume receiving 80%, 90%, 100%, 150%, and 200% of the prescribed dose, respectively)
  • The rectal and urethral doses

Urbanic et al reported that a review of 4 series confirms that freedom from recurrence depends on adequate dosimetry.[10]

Outcome and Prognosis

When compared with historical series using classic external beam radiation therapy (EBRT) to treat prostate cancer, brachytherapy series appear to offer equivalent or better disease-specific survival as measured by biochemical failure rates. Patients must be appropriately selected and treated at an accredited institution. Although brachytherapy is still in its infancy, 5-, 7-, and 12-year follow-up studies suggest brachytherapy is equal to surgery in terms of biochemical recurrence.

A 12-year study by Ragde et al (2000) reported on patients treated with I-125 seeds, with or without additional EBRT.[11] Of these patients, 66% and 79% of the brachytherapy alone and external radiation plus brachytherapy groups, respectively, were free of biochemical or clinical recurrence.

Similarly, Kuban et al found no evidence of disease in only 64% of patients treated with iodine-125 at 10-year follow-up, but negative findings were found in all of these patients after posttreatment prostate biopsy.[12] In patients with positive findings after prostate biopsies, only 19% remained actuarially disease-free at 10 years.

Polascik et al compared brachytherapy with radical prostatectomy and demonstrated that, at 7 years, surgery had an 87% progression-free survival rate versus 79% for brachytherapy in comparable patients.[13] High-risk patients have been reported to have progression-free survival rates of 65-80%. When evaluating these control rates, careful attention must be given to variables such as the addition of EBRT or androgen ablation and length of follow-up.

However, no prospectively performed randomized studies have compared the efficacy of surgery with that of either brachytherapy or high-dose external beam radiotherapy as delivered with modern treatment techniques. Because of a known migration in stage and histology between biopsy and prostatectomy specimens, any retrospective advantage must be interpreted with caution owing to differences in clinical versus pathologic staging.

The Partin tables are the best nomogram for predicting prostate cancer spread and prognosis.

Complications of Brachytherapy

Perineal, urinary, and rectal symptoms and sexual dysfunction may complicate brachytherapy.

Perineal symptoms

The perineum is tender and bruised and may have slight bleeding at needle puncture sites. Treatment is predominantly with ice and mild analgesics.

Urinary symptoms

Hematuria is expected for the first 1-2 weeks, and all patients experience dysuria. Irritative symptoms such as dysuria, frequency, and urgency last from days to months. Studies have shown that 34-45% of patients have symptoms that persist for up to 1 year.

The incidence rate of incontinence is 10-35% in the first few months. Few patients have any leakage at 1 year.

In most cases, perioperative edema resolves within the first 48 hours or certainly within the first week. A small subset of patients continues to have difficulty voiding beyond that period. These patients are taught the technique of clean intermittent catheterization.

If voiding does not return within 3 months, urodynamics testing may be considered to ensure that this is truly obstruction rather than bladder dysfunction. If obstructive symptoms are present, patients are started on alpha-blockers and maintained on this therapy for 9 months. In patients with true obstruction, transurethral resection of the prostate may be performed.

Rectal symptoms

As many as a third of patients report urge, diarrhea, and painful bowel movements. These symptoms improve over the first year. Nonsteroidal anti-inflammatory drugs and mesalamine (Rowasa) suppositories may help.

At 1 year, only 2% have persistent symptoms. Some studies report as many as 20% of patients have bright-red blood per rectum. Symptoms have been reported to persist as long as 49 months after the procedure.

Prostatorectal fistulas occur in 1-7% of all patients in published series. Recent data from the primary authors’ institution suggest that, after brachytherapy, these fistulas result from biopsy of the anterior rectal wall by gastroenterologists. The wall likely appears irritated and ulcerated following brachytherapy, thus prompting the biopsy. Patients should be counseled to undergo colonoscopy prior to or 1 year after brachytherapy.

Sexual dysfunction

Generally, 33% of patients have a decrease in sexual function and activity. Decreased semen volume is observed. Results from studies on impotence vary, with rates as widely disparate as 2.5-25%. In some studies, 40% of the patients experienced some degree of erectile dysfunction following radiation therapy.

Long-Term Monitoring

Prostate-specific antigen (PSA) levels should be measured and a digital rectal examination (DRE) should be performed every 3-6 months for 5 years and then yearly. If the PSA or DRE findings are abnormal at follow-up, appropriate increased follow-up frequency (PSA abnormality only) or biopsy (DRE abnormality) should be considered.

The PSA definition of disease freedom after radiotherapy for prostate cancer is still disputed. Historically, several different approaches have been used to define biochemical failure.

The first approach is to use absolute values to define failure, similar to the use of PSA levels following prostatectomy. Various cutoffs have been used, ranging from 4-0.2 ng/mL. The alternative approach is to use increasing values of PSA over time as a definition of failure.

The American Society for Therapeutic Radiology and Oncology (ASTRO) has proposed that 3 consecutive elevations should define failure if each elevation satisfies certain requirements. A principal rationale behind the ASTRO definition is the well-documented occurrence of benign spikes in PSA levels that can occur following brachytherapy; allowing for these spikes prevents an incorrect diagnosis of a recurrence.

Recent studies have shown that the ASTRO Consensus Panel definition of biochemical failure following radiation therapy correlates well with clinical distant metastases–free survival, DFS, and cause-specific survival. These findings suggest that this definition may be a surrogate for clinical progression and survival.

However, determining the date of recurrence has been controversial. In the ASTRO definition, the date of failure is the point halfway between the nadir and first rise in PSA level. This ambiguity and the fact that the definition performed poorly in patients treated with hormone ablation has led to the development of a new definition. The Phoenix definition is characterized by a rise in PSA level of 2 ng/mL above the nadir. This is used to define biochemical failure after EBRT, with or without hormone ablation.

Both definitions are currently used in brachytherapy research protocols. Regardless of the definition used, the reported date of biochemical control should be cited as 2 years short of the median follow-up. In other words, prolonged follow-up is necessary in good studies.

The faster the PSA level nadir is reached, the better the outcomes.

The following are the PSA level nadir levels with the corresponding 5-year disease-free survival rates:

  • PSA level less than 0.5 ng/mL – 79%
  • PSA level 0.5-0.99 ng/mL – 66%
  • PSA level 1-1.99 ng/mL – 49%
  • PSA level greater than 2 ng/mL- 25%

Quality of life

The American Brachytherapy Society (ABS) recommends using validated, patient-administered health-related quality-of-life methods to evaluate baseline and follow-up bowel, urinary, and sexual dysfunction. Studies have shown that, over time, quality of life among patients who have undergone radical prostatectomy is comparable to that of patients who have undergone brachytherapy alone. Initial differences in the adverse-effect profile dissipate over time (2-4 y).

However, the quality of life in patients treated with brachytherapy and intensity-modulated radiation therapy was significantly worse at all time points compared with that in patients treated with radical prostatectomy and brachytherapy alone. The effect of androgen ablation on health-related quality of life is mixed, with some studies suggesting a worsening of health-related quality of life and others finding no discernible change.

 

 

Alternative Medicine

By Mayo Clinic staff

No complementary or alternative treatments will cure prostate cancer. However, complementary and alternative prostate cancer treatments may help you cope with the side effects of cancer and its treatment.

Alternative prostate cancer treatments that may help you cope with the stress and anxiety you may experience after your diagnosis include:

  • Art therapy
  • Dance or movement therapy
  • Exercise
  • Meditation
  • Music therapy
  • Relaxation techniques, such as guided imagery or muscle relaxation
  • Spirituality

Ask your doctor to refer you to a professional who can help you learn to do these activities. Some require instruction, while others can be done on your own.

 

 

Pomegranate Juice: A Cure for Prostate Cancer?

Is it true that pomegranate juice may slow the growth of prostate cancer? How much should I drink?

Answer

from Erik P. Castle, M.D., Mayo Clinic

Some research suggests that drinking pomegranate juice may slow the progression of prostate cancer.

For example, in one study, the length of time it took for prostate-specific antigen (PSA) to double after surgery or radiation for prostate cancer was significantly longer in men who drank 8 ounces (237 milliliters) of pomegranate juice daily for up to two years. A longer PSA doubling time indicates that the cancer may be progressing less rapidly. Other studies have found that certain compounds in pomegranate juice inhibited growth of prostate cancer cells in the laboratory.

Although these results are encouraging, they’re only preliminary. Clinical trials are under way, and it’s too early to say if pomegranate juice can definitely slow the growth of prostate cancer. It’s also unclear whether drinking pomegranate juice alters the course of prostate cancer overall so that men live longer or better.

If you choose to drink pomegranate juice, talk with your doctor first. Although pomegranate juice is generally safe, there is evidence that it affects the metabolism of several prescription medications, including the blood thinner warfarin (Coumadin) and some drugs used to treat high blood pressure and high cholesterol.

 

JAMA:
The Journal of the American Medical Association
jama.ama-assn.org

Original Contribution
JAMA. 2011;306(11):1205-1214. doi: 10.1001/jama.2011.1333

 

 

Prediction of Erectile Function Following Treatment for Prostate Cancer

  1. Mehrdad Alemozaffar, MD;
  2. Meredith M. Regan, ScD;
  3. Matthew R. Cooperberg, MD, MPH;
  4. John T. Wei, MD;
  5. Jeff M. Michalski, MD;
  6. Howard M. Sandler, MD;
  7. Larry Hembroff, PhD;
  8. Natalia Sadetsky, PhD;
  9. Christopher S. Saigal, MD, MPH;
  10. Mark S. Litwin, MD, MPH;
  11. Eric Klein, MD;
  12. Adam S. Kibel, MD;
  13. Daniel A. Hamstra, MD;
  14. Louis L. Pisters, MD;
  15. Deborah A. Kuban, MD;
  16. Irving D. Kaplan, MD;
  17. David P. Wood, MD;
  18. Jay Ciezki, MD;
  19. Rodney L. Dunn, MS;
  20. Peter R. Carroll, MD, MPH;
  21. Martin G. Sanda, MD

[+] Author Affiliations

  1. 1.  Author Affiliations: Urology Division (Drs Alemozaffar and Sanda) and Radiation Oncology Department (Dr Kaplan), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard Medical School (Dr Regan); Department of Urology, University of California, San Francisco (Drs Cooperberg, Sadetsky, and Carroll); Departments of Urology (Drs Wei and Wood) and Radiation Oncology (Dr Hamstra) and Biostatistics Core (Mr Dunn), School of Medicine, University of Michigan, Ann Arbor; Departments of Radiation Oncology (Dr Michalski) and Surgery (Dr Kibel), Washington University, St Louis, Missouri; Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California (Dr Sandler); Office for Survey Research, Institute for Public Policy and Social Research, Michigan State University, East Lansing (Dr Hembroff); Departments of Urology (Drs Saigal and Litwin) and Health Services (Dr Litwin), UCLA Center for Health Sciences, Los Angeles; Glickman Urological and Kidney Institute (Dr Klein) and Department of Radiation Oncology (Dr Ciezki), Cleveland Clinic Hospitals, Cleveland, Ohio; and Departments of Urology (Dr Pisters) and Radiation Oncology (Dr Kuban), M.D. Anderson Cancer Center, Houston, Texas.

Abstract

Context Sexual function is the health-related quality of life (HRQOL) domain most commonly impaired after prostate cancer treatment; however, validated tools to enable personalized prediction of erectile dysfunction after prostate cancer treatment are lacking.

Objective To predict long-term erectile function following prostate cancer treatment based on individual patient and treatment characteristics.

Design Pretreatment patient characteristics, sexual HRQOL, and treatment details measured in a longitudinal academic multicenter cohort (Prostate Cancer Outcomes and Satisfaction With Treatment Quality Assessment; enrolled from 2003 through 2006), were used to develop models predicting erectile function 2 years after treatment. A community-based cohort (community-based Cancer of the Prostate Strategic Urologic Research Endeavor [CaPSURE]; enrolled 1995 through 2007) externally validated model performance. Patients in US academic and community-based practices whose HRQOL was measured pretreatment (N = 1201) underwent follow-up after prostatectomy, external radiotherapy, or brachytherapy for prostate cancer. Sexual outcomes among men completing 2 years’ follow-up (n = 1027) were used to develop models predicting erectile function that were externally validated among 1913 patients in a community-based cohort.

Main Outcome Measures Patient-reported functional erections suitable for intercourse 2 years following prostate cancer treatment.

Results Two years after prostate cancer treatment, 368 (37% [95% CI, 34%-40%]) of all patients and 335 (48% [95% CI, 45%-52%]) of those with functional erections prior to treatment reported functional erections; 531 (53% [95% CI, 50%-56%]) of patients without penile prostheses reported use of medications or other devices for erectile dysfunction. Pretreatment sexual HRQOL score, age, serum prostate-specific antigen level, race/ethnicity, body mass index, and intended treatment details were associated with functional erections 2 years after treatment. Multivariable logistic regression models predicting erectile function estimated 2-year function probabilities from as low as 10% or less to as high as 70% or greater depending on the individual’s pretreatment patient characteristics and treatment details. The models performed well in predicting erections in external validation among CaPSURE cohort patients (areas under the receiver operating characteristic curve, 0.77 [95% CI, 0.74-0.80] for prostatectomy; 0.87 [95% CI, 0.80-0.94] for external radiotherapy; and 0.90 [95% CI, 0.85-0.95] for brachytherapy).

Conclusion Stratification by pretreatment patient characteristics and treatment details enables prediction of erectile function 2 years after prostatectomy, external radiotherapy, or brachytherapy for prostate cancer.

………………………………………………………………………………………

 

 

Biopsy and Gleason Score

A pathologist looks for cell abnormalities and “grades” the tissue sample from 1 to 5. The sum of 2 Gleason grades is the Gleason score. These scores help determine the chances of the cancer spreading. They range from 2, less aggressive, to 10, a very aggressive cancer. Gleason scores helps guide the type of treatment your doctor will recommend.

 

 

 

 

Prostate Cancer Imaging

Some men may need additional tests to see if the cancer has spread beyond the prostate. These can include ultrasound, a CT scan, or an MRI scan (seen here). A radionuclide bone scan traces an injection of low-level radioactive material to help detect cancer that has spread to the bone.

In the MRI scan shown here, the tumor is the green, kidney-shaped mass in the center, next to the prostate gland (in pink).

 

 

 

Food For Health

 

 

Food for Health

A cancer-conscious diet may be the best choice for survivors who want to bolster their health and those hoping to lower their risk. That means:

  • Five or more fruits and veggies a day
  • Whole grains instead of white flour or white rice
  • Limit high-fat meat
  • Limit or eliminate processed meat (hot dogs, cold cuts, bacon)
  • Limit alcohol to 1-2 drinks per day (if you drink)

Foods high in folate may have some action against prostate cancer (spinach, orange juice, lentils). Studies found mixed results on lycopene, an antioxidant found in tomatoes.