Prostate cancer


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Definition

Prostate cancer tends to occur most commonly in men over the age of 50. It is the most common cancer diagnosed among American men, accounting for nearly 200,000 new cancer cases in the United States each year.

Alternate names

Adenocarcinoma of the prostate

Causes, incidence and risk factors

Prostate cancer tends to occur most commonly in men over the age of 50, and greater than 65 percent of all cases are diagnosed in men 65 years and older. The incidence of prostate cancer increases with age; the lifetime risk for the average American man is about 1 in 6, but only 8 percent of men develop prostate cancer between the ages of 50 and 70 years. Well-established risk factors include older age, family history and race (African-Americans are at greater risk). Other potential risk factors thought to be associated prostate cancer include a Western diet high in saturated fat, and obesity.

Types

The overwhelming majority of prostate cancers are adenocarcinomas, which arises from the glandular (acinar) component of the prostate.

Other rare and atypical types of prostate cancer include:

  • Ductal carcinoma
  • Mucinous carcinoma
  • Signet-ring cell carcinoma
  • Small cell carcinoma
  • Clear cell adenocarcinoma
  • Giant cell carcinoma

These rare and atypical variants often act aggressively and may respond differently to therapy than the more common prostate adenocarcinoma. As they are rare, however, most men are unaffected by these atypical variants.

Prostate cancer has changed significantly over the past two decades. Most prostate cancers are now diagnosed in patients at an earlier stage and younger age compared with 20 years ago, largely because of the widespread evaluation of prostate specific antigen, or PSA, levels. Although prostate cancer deaths have decreased in recent years, PSA screening continues to be controversial.

Localized Prostate Cancer

Approximately 90 percent of prostate cancers are diagnosed at a localized stage (cancer confined to prostate without evidence of spread). Localized cancers are most commonly detected through an elevation in PSA level and typically do not cause symptoms. Less commonly, prostate cancer may be detected by an abnormal digital rectal exam, or DRE, or after urinary symptoms, such as hematuria (blood in the urine) or problems with urination (difficulty or discomfort with urination), are noted.

Not all local prostate cancers are the same. Some are indolent and will not cause problems, whereas others are clinically significant and require treatment. Even among more relevant cancers, there are differences that further separate cancers by risk (for example, low-, intermediate- and high-risk prostate cancer). Factors that determine the risk and clinical significance of prostate cancer include PSA, Gleason grade and disease stage.

There are several effective treatment options for men with clinically significant local prostate cancer, including surgery, external radiation therapy and interstitial brachytherapy. Treatment recommendations are usually based on a number of factors, including disease characteristics, risk category, candidacy for a particular treatment and patient preference. In some cases (low- and intermediate-risk prostate cancer, for example), a single treatment may be adequate for disease control. For others, particularly in high-risk prostate cancer, a combination of treatments may be required. For low-risk prostate cancer and among older men, active-surveillance (observation) is another management option.

Although effective in controlling cancer, most treatments carry some risk of impacting urinary, sexual and bowel health. Newer treatment methods, however, continue to be developed to minimize the risks of these side effects (for example, nerve-sparing radical prostatectomy). After treatment, approximately 15 percent to 25 percent of patients with early-stage (localized) prostate cancer experience a biochemical (PSA) recurrence, indicating possible need for additional therapy. However, the overall five-year survival for patients with localized prostate cancer is close to 100 percent.

Advanced Prostate Cancer

Approximately 10 percent of prostate cancers are diagnosed at an advanced stage, characterized by involvement of surrounding structures, spread to lymph nodes or metastasis to more distant sites. Advanced prostate cancer more commonly causes some symptoms, such as hematuria, urinary obstruction or bone pain.

Treatment options for patients with metastatic prostate cancer are more limited, although in some settings, surgery or radiation therapy may still be indicated. More commonly, androgen deprivation therapy, or ADT, also known as hormone therapy, is used to control metastatic disease and slow the growth of more advanced prostate cancers. Chemotherapy may also be used to manage patients with metastatic prostate cancer, although it is not a mainstay of management. Common sites of metastatic spread include the bone, liver and lungs. The overall five-year survival for regionally advanced and metastatic prostate cancer is approximately 32 percent.

Signs and symptoms

For most men, prostate cancer does not cause symptoms but is detected because of an elevation in prostate specific antigen, or PSA. However, symptoms of the lower urinary tract, such as hematuria (blood in the urine), frequency (need to urinate frequently) and dysuria (discomfort or pain with urination) may be signs of prostate problems, including prostate cancer.

Other uncommon symptoms of prostate cancer can include urinary retention, weight loss, abdominal pain, bone pain or fracture.

Lower Urinary Tract Symptoms (Prostatism)

  • Frequency
  • Urgency
  • Hematuria (visible or microscopic)
  • Dysuria
  • Urinary retention

Pain Symptoms

  • Back pain
  • Pelvic pain
  • Bone pain

Constitutional Symptoms

  • Weight loss

Diagnostic Tests

  • Physical examination
  • PSA blood test
  • Prostate biopsy
  • Abdominal and pelvic CT scan
  • Bone scan (if indicated)

After taking a detailed medical history and performing a physical examination, including a digital rectal examination, a PSA blood test will be performed. If the PSA level is elevated, a prostate biopsy will be recommended. The biopsy is an outpatient procedure (you go home the same day) that is performed with local anesthesia. Several samples of tissue are obtained from the prostate. These samples are what tell us if you have prostate cancer. If the biopsy is positive, other tests may be performed on the basis of your PSA level, cancer grade and findings on exam. Most commonly, a CT scan of the abdomen and pelvis will be obtained for clinical staging. In high-risk cases, a bone scan may be recommended to determine if there has been spread to the bones.

Tests

Clinical staging is performed with physical examination and abdominal and pelvic CT scan. In cases of advanced or high-risk disease, additional testing such as a bone scan may be necessary.

The prognosis of prostate cancer is directly linked to the stage of disease. Staging is a process that demonstrates how far the cancer has spread. Both treatment options and prognosis (or outlook) for prostate cancer depend significantly on the stage of disease.

Treatments

Most prostate cancers are localized and can be treated with surgery, external radiation therapy or interstitial brachytherapy. In low-risk disease, observation or active surveillance may also be an option. Focal therapy using ablative technology is less common and is currently under investigation.

Treatments for localized prostate cancer include:

  • 3D-conformal radiation therapy
  • Active surveillance (observation)
  • Focal therapy
  • Intensity-modulated radiation therapy
  • Interstitial brachytherapy
  • Radical perineal prostatectomy
  • Radical retropubic prostatectomy
  • Robotic-assisted laparoscopic prostatectomy
  • Salvage therapy

3D conformal and Intensity-Modulated Radiation Therapy

Radiation therapy is an effective treatment for prostate cancer and can be used to manage low- and high-risk cases. Currently, two types of external radiation therapy are used. 3D-conformal RT targets the prostate with the aid of imaging guidance to more accurately deliver radiation dose to the prostate with less radiation therapy exposure to surrounding tissues. Intensity-modulated RT uses more advanced technology to reduce dose to the areas of the bladder, rectum and bowel and boost dose to the prostate. For both modalities, a total radiation dose of 76 Gy should be administered, and some studies have shown that higher doses are more effective. Radiation therapy is typically given in daily fractions over the course of 10 weeks. In intermediate- and high-risk prostate cancer, RT should be administered with androgen deprivation therapy to maximize the treatment effect.

Active surveillance (observation)

Active surveillance is used in some cases of low-risk disease, as well as among older patients for whom active treatment with surgery or radiation therapy may not be possible or necessary. Active surveillance is most often used because some prostate cancers may never become life-threatening. PSA and digital rectal exams, or DRE, are typically checked periodically, and current active surveillance protocols recommend repeat biopsies to ensure that disease does not progress.

Interstitial prostate brachytherpay involves placement of small radioactive pellets, or “seeds” into the prostate. In general, this treatment can be used for small to normal sized prostates and for Gleason Grade 6 or less tumors. In settings of higher-risk disease (PSA>10 ng/mL or Gleason Grade 7) where there is concern for extraprostatic extension, external radiation therapy should be used in conjunction with interstitial bracytherapy to ensure adequate cancer control. In some cases, hormone therapy may be used before brachytherapy to help reduce the size of the prostate.

Focal therapy

Ablative therapies such as cryoablation, radiofrequency ablation and high-frequency ultrasonic ablation are currently being studied as a way to limit treatment to the focal location of the cancer instead of treating the entire prostate with the hopes that focal therapy will be associated with fewer side effects than other nonfocal treatments. Selection of appropriate, low-risk patients is essential because less therapy may not be adequate to control higher-volume or high-risk prostate cancer. Other concerns regarding focal therapy include targeting the tumor within the prostate accurately, identifying other areas of cancer within the prostate and offering more effective management compared with active surveillance.

Radical perineal prostatectomy

Radical perineal prostatectomy consists of removal of the prostate through an incision in the perineum (the area between the scrotum and anus), and was the first surgical approach used to treat prostate cancer. Today, perineal prostatectomy is relatively uncommon, but it is still used in certain cases, such as in obese patients in which access to the prostate from pelvis would be difficult. In intermediate- and high-risk cases in which lymph node dissections are indicated, a separate lymph node dissection may be indicated to complete staging. Because it is an uncommon surgery, the surgeon should be experienced in this surgical approach.

Radical retropubic prostatectomy

Radical retropubic prostatectomy consists of removal of the prostate gland and surrounding lymph nodes through an 8 cm open incision above the pubic bone. Radical retropubic prostatectomy is the most common open surgical approach to treating prostate cancer, and can be used to treat a range of prostate cancer, including low-, intermediate- and high-risk localized prostate cancer, as well as radiation refractory prostate cancer (termed salvage prostatectomy). Most patients spend one to two nights in the hospital and are sent home with a urinary (Foley) catheter, which stays in for a week following surgery to encourage healing of the urethra. Depending on the stage and risk of the disease, radical retropubic prostatectomy can be performed with nerve-sparing techniques. Nerve-sparing prostatectomy provides the best chance of the return of erections after surgery in men with good erectile function prior to treatment, and is typically used in patients who have low- and intermediate-risk disease. In the setting of high-risk disease, however, the nerve-sparing approach may not be indicated as it may limit cancer control (removal of all cancer tissue). Like other types of surgical therapy, outcomes after radical retropubic prostatectomy (cancer control, urinary continence, erectile function and complications) tend to be better, on average, when performed by high-volume and fellowship-trained surgeons.

Robotic-assisted laparoscopic prostatectomy

Robotic-assisted laparoscopic prostatectomy is one of the most common types of surgical treatments for prostate cancer, and its use in the management of localized prostate cancer has increased rapidly in recent years. The robotic approach takes advantage of the benefits of laparoscopy as well as small surgical working elements that replicate the movement of the human hand. In general, this option is associated with less blood loss, a lower chance of requiring a blood transfusion, decreased pain postoperatively and a shorter convalescence. As with radical retropubic prostatectomy, lymph nodes are removed with the prostate for pathologic staging. Patients tend to spend one to two nights in the hospital and are sent home with a urinary (Foley) catheter that stays in place for seven to 10 days. As with open surgery, this procedure should be performed by a surgeon familiar with the robot and who is trained in performing radical prostatectomy. In general, high-volume (those surgeons who perform many procedures) and fellowship surgeons tend to have better outcomes than low-volume and non-fellowship-trained surgeons.

Salvage therapy

In cases of prostate cancer recurrence following primary treatment, a secondary local therapy can lead to salvage and cure. Depending on which type of treatment was first used, salvage surgery, radiation therapy or cyroabalation may be used to control recurrent disease.

Prevention

While prostate cancer screening is not endorsed universally, the American Cancer Society and American Urologic Association recommend that most men begin screening at age 50 and at 40 years of age for those who are African-American or who have a family history of the disease.

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