AUTHOR AND EDITOR INFORMATION

Section 1 of 15  

• Authors and Editors
• Introduction
• Relevant Anatomy
• Histologic Findings and the Tumor Node Metastases (TNM) Staging System
• Treatment
• Nonsurgical Therapy
• Medication
• Surgical Therapy
• Follow-up
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Multimedia
• References

INTRODUCTION

Section 2 of 15  

• Authors and Editors
• Introduction
• Relevant Anatomy
• Histologic Findings and the Tumor Node Metastases (TNM) Staging System
• Treatment
• Nonsurgical Therapy
• Medication
• Surgical Therapy
• Follow-up
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Multimedia
• References

Prostate cancer is one of the most common cancers among males and is the second leading cause of cancer-related death in males. Because of continuing advances, the diagnosis and treatment of prostate cancer is constantly evolving. This article provides an overview of the therapeutic options available to men with localized forms of this disorder, highlighting the following:

• The biopsy grade, clinical stage, and prostate-specific antigen (PSA) level provide prognostic information that helps stratify patients to particular treatments, including watchful waiting, hormonal therapy, and potentially curative therapies (eg, radiation, surgery).
• The treatment of prostate cancer requires the patient to thoroughly analyze the risks and benefits of each option, enabling him to choose the right therapy.
• The final section is dedicated to the future diagnostic and therapeutic modalities that are currently used on an investigational basis.

RELEVANT ANATOMY

Section 3 of 15  

• Authors and Editors
• Introduction
• Relevant Anatomy
• Histologic Findings and the Tumor Node Metastases (TNM) Staging System
• Treatment
• Nonsurgical Therapy
• Medication
• Surgical Therapy
• Follow-up
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Multimedia
• References

The prostate lies below the bladder and encompasses the prostatic urethra (see Image 1). It is surrounded by a capsule and is separated from the rectum by a layer of fascia termed the Denonvilliers aponeurosis.

The inferior vesical artery, which is derived from the internal iliac artery, supplies blood to the base of the bladder and prostate. The capsular branches of the inferior vesical artery help identify the pelvic plexus arising from the S2-4 and T10-12 nerve roots. The neurovascular bundle lies on either side of the prostate on the rectum. It is derived from the pelvic plexus and is important for erectile function.

HISTOLOGIC FINDINGS AND THE TUMOR NODE METASTASES (TNM) STAGING SYSTEM

Section 4 of 15  

• Authors and Editors
• Introduction
• Relevant Anatomy
• Histologic Findings and the Tumor Node Metastases (TNM) Staging System
• Treatment
• Nonsurgical Therapy
• Medication
• Surgical Therapy
• Follow-up
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Multimedia
• References

Prostate adenocarcinoma

The most commonly used system of classifying the histologic characteristics of prostate cancer is the Gleason score. The classification is determined by the glandular architecture within the tumor. The system assigns a grade of 1-5 to the predominant pattern and the second most common pattern. The sum of these 2 grades is referred to as the Gleason score. Scoring based on the 2 most common patterns is an attempt to factor in the considerable heterogeneity within prostate cancers. In addition, this scoring method is superior to the individual grades alone in predicting disease outcomes.

Grades are based on the extent to which the epithelium assumes a normal glandular structure. Grade 1 indicates a near-normal pattern, and grade 5 indicates the absence of any glandular pattern (less malignant to more malignant). Grades 2-4 are considered low grade; grades 5-7 are considered moderate grade; and grades 8-10 are considered high grade. This scheme of grading histological features greatly depends on the skill and experience of the pathologist and is thus subject to some degree of individual variation.

Although the change in glandular architecture represented by the Gleason score is the most widely used and correlative histological parameter, it is by no means the only histological change that can be observed in prostate cancers. Indeed, notable changes in cell and nuclear morphology, DNA ploidy, neuroendocrine differentiation, and vascularity can be observed and may have prognostic significance.

High-grade prostatic intraepithelial neoplasia

A prostatic intraepithelial neoplasia (PIN) is the putative precancerous end of the morphologic continuum of cellular proliferations within prostatic ducts, ductules, and acini. Experts identify 2 grades of PIN, low grade and high grade. High-grade PIN is considered a precursor to invasive carcinoma and may also coexist with cancer in the same gland. The continuum, which culminates in high-grade PIN and early invasive cancer, is characterized by basal cell layer disruption, basement membrane disruption, progressive loss of secretory differentiation markers, increasing nuclear and nucleolar abnormalities, increasing proliferative potential, and increasing variation in DNA content (ie, aneuploidy).

Clinical studies suggest that PIN predates carcinoma by 10 years or more. The clinical importance of recognizing PIN is based on its concomitant association with carcinoma; therefore, if it is identified in prostate biopsy specimens, a thorough search for concurrent invasive carcinoma is warranted.

Staging

The 2002 tumor node metastases (TNM) staging system is used to stage prostate cancer. Compared with previous iterations of this system, the 2002 revision has 2 important differences. First, it reverts back to 3 clinical stages of localized T2 disease, as was the case for the 1992 system, and second, it recommends the use of the Gleason scoring system for grading.

• T - Primary tumor
• • TX - Primary tumor cannot be assessed
  • T0 - No evidence of primary tumor
  • T1 - Clinically inapparent tumor not palpable or visible by imaging
  • T1a - Tumor incidental histologic finding in less than or equal to 5% of tissue resected
  • T1b - Tumor incidental histologic finding in greater than 5% of tissue resected
  • T1c - Tumor identified by needle biopsy (because of elevated PSA level); tumors found in 1 or both lobes by needle biopsy but not palpable or reliably visible by imaging
  • T2 - Tumor confined within prostate
  • T2a - Tumor involving less than or equal to half a lobe
  • T2b - Tumor involving more than half a lobe but not more than one lobe
  • T2c - Tumor involving both lobes
  • T3 - Tumor extending through the prostatic capsule; no invasion into the prostatic apex or into, but not beyond, the prostatic capsule
  • T3a - Extracapsular extension (unilateral or bilateral)
  • T3b - Tumor invading seminal vesicle(s)
  • T4 - Tumor fixed to or invading adjacent structures other than seminal vesicles (eg, bladder neck, external sphincter, rectum, levator muscles, pelvic wall)
• NX - Regional lymph nodes (cannot be assessed)
• • N0 - No regional lymph node metastasis
  • N1 - Metastasis in regional lymph node or nodes

Regional lymph nodes are assessed via surgical removal or biopsy of the pelvic lymph nodes, including the obturator chain. The surgical boundaries include the bifurcation of the common iliac, the obturator nerve, and the node of Cloquet.

• Distant metastasis
• • PM1c - More than 1 site of metastasis present
  • MX - Distant metastasis cannot be assessed
  • M0 - No distant metastasis
  • M1 - Distant metastasis
  • M1a - Nonregional lymph node(s)
  • M1b - Bone(s)
  • M1c - Other site(s)

TREATMENT

Section 5 of 15  

• Authors and Editors
• Introduction
• Relevant Anatomy
• Histologic Findings and the Tumor Node Metastases (TNM) Staging System
• Treatment
• Nonsurgical Therapy
• Medication
• Surgical Therapy
• Follow-up
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Multimedia
• References

Standard treatments for localized prostate cancer include surgery, radiation therapy (external beam or brachytherapy with and without androgen ablation), or observation, which is also termed watchful waiting. Three significant factors enter into the decision for the selection of therapy.

• First, the overall life expectancy of patients as determined by age and comorbidities
• Second, the biological characteristics of the tumor, together with its predicted aggressiveness and behavior
• Third, the preferences of the patient for the various treatment options, with consideration of complications, adverse effects, relative efficacy, and quality-of-life issues

With respect to the tumor characteristics, models have been developed that combine the clinical stage (as determined by digital rectal examination [DRE] findings), Gleason score after biopsy, and serum concentration of PSA in an attempt to better predict which men have organ-confined cancer as opposed to those who may have local extension. In addition, these models can be used to predict the time to biochemical failure and the time to the development of clinical metastatic disease in patients with rising PSA levels.

In addition, these models have been adapted to personal-computer and handheld-computer platforms and can be used with ease in clinical practice. One such program can be downloaded free of charge from the Prostate Nomogram section of the Memorial Sloan-Kettering Cancer Center Web site. The Partin tables are another excellent nomogram for predicting prostate cancer spread and prognosis.

NONSURGICAL THERAPY

Section 6 of 15  

• Authors and Editors
• Introduction
• Relevant Anatomy
• Histologic Findings and the Tumor Node Metastases (TNM) Staging System
• Treatment
• Nonsurgical Therapy
• Medication
• Surgical Therapy
• Follow-up
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Multimedia
• References

Early localized disease (clinical stage T1-2N0M0)

• Watchful waiting
• • See Prostate Cancer: Biology, Diagnosis, Pathology, Staging, and Natural History.
  • Watchful waiting, a program of regular examinations, PSA monitoring, and DREs, is considered in patients of advanced age or those who have significant life-limiting comorbidities and a life expectancy of less than 15 years. In addition, watchful waiting is appropriate in patients who do not harbor well-differentiated tumors.
  • Recent evidence supports these recommendations, and further evidence suggests that patients who undergo watchful waiting for more than 15 years sustain significant disease progression.
• Androgen ablation
• • Androgen ablation has been used in some patients who are unwilling to undergo potentially curative treatment options yet want some form of treatment beyond watchful waiting.
  • Androgen ablation can be performed in multiple ways, such as via luteinizing hormone–releasing hormone agonists, luteinizing hormone–releasing hormone antagonists, or oral antiandrogens (steroidal and nonsteroidal; see Medication).
  • In 2002, See et al reported early results from studies using the antiandrogen bicalutamide (Casodex).¹
• External beam radiation therapy
• • This is used with curative intent in patients with clinically localized cancer and is often combined with androgen ablation.
  • Techniques include (1) conventional external beam (4-field box); (2) conformal external beam, which delivers higher doses of radiation to the prostate while sparing adjacent tissues better than the conventional approach; and (3) intensity-modulated radiation therapy, which is a highly conformal treatment technique for radiation treatment planning and delivery; the increased control permits higher doses with reduced acute and late toxicities.
  • External beam radiation therapy can be used concomitantly with androgen ablation.
  • • Several Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer trials have determined that androgen ablation, when combined with external radiation, yields improved disease-specific survival and increased time to recurrence in patients with locally advanced or high-grade prostate cancer. The advantage of this approach in patients with early disease remains to be determined, but it could offer significant advantages when used in younger patients with significant expected longevity (>20 y).
    • Androgen ablation has traditionally been achieved with luteinizing hormone–releasing hormone agents combined with antiandrogens, although variations on this theme have been described. Androgen ablation commonly begins several months before radiation is initiated and continues for several months or years afterward.
    • In the Radiation Therapy Oncology Group 85-31 study, 945 analyzable subjects (477 in adjuvant arm, 468 in observation arm) had a median follow-up of 4.5 years. Actuarial projections showed that, at 5 years, 84% in the adjuvant goserelin arm and 71% in the observation arm still had no evidence of local recurrence. The corresponding figures for freedom from distant metastases and disease-free survival are 83% versus 70% and 60% versus 44%, respectively. If PSA levels greater than 1.5 ng/mL are included as failures in these rates, the 5-year disease-free survival rate is 53% in the adjuvant goserelin arm and 20% in the observation arm. The 5-year survival rate (for the entire population) is 75% in the adjuvant arm and 71% in the observation arm. However, in patients with tumors with a Gleason score of 8-10, the difference in actuarial 5-year survival (66% in the adjuvant goserelin arm vs 55% in the observation arm) reaches statistical significance.
  • Complications of external radiotherapy include cystitis, proctitis, enteritis, impotence, urinary retention, and incontinence (7-10%). Patients also exhibit the symptoms of androgen deprivation (eg, decreased libido, impotence, hot flashes) if undergoing this form of therapy in conjunction with radiation therapy.
• Brachytherapy
• • See Prostate Cancer: Brachytherapy (Radioactive Seed Implantation Therapy).
  • Types of brachytherapy include low–dose rate brachytherapy and high–dose rate brachytherapy.
  • In the low–dose rate type, radioactive palladium or iodine seeds are placed into the prostate. In the high–dose rate type, temporary implants are placed in the prostate. The theoretical advantage is the capacity to optimize the dose after needles are in place. Improved outcomes compared with permanent brachytherapy have not been demonstrated to date.
  • Either type may be used alone or in combination with external beam radiotherapy, depending on the PSA level and the cancer grade. Most practitioners do not use brachytherapy in conjunction with external beam therapy in patients with early (well-differentiated) localized disease and low (<10 ng/mL) PSA levels. In more advanced cases, external beam therapy with or without neoadjuvant and adjuvant androgen ablation is used.
  • Complications of brachytherapy are generally similar to those of conformal or intensity-modulated external radiotherapy.
• Transperineal cryotherapy
• • See Prostate Cancer: Cryotherapy.
  • Low temperatures have been used for centuries in the form of ice packs. In the 1960s, liquid nitrogen enabled physicians to achieve temperatures of -190°C (-310°F). Advances in insulated probes have allowed urologists to freeze a specific zone of tissue, causing necrosis in that area.
  • The mechanism of cell death due to cryotherapy involves 3 processes—direct mechanical shock, osmotic shock, and cellular hypoxia. The freezing process entails a freeze-thaw cycle that leads to mechanical shearing, which, in turn, disrupts cell membranes and allows them to become permeable and responsive to the osmotic forces in the intracellular space. This leads to hyperosmotic shock and causes shrinkage and protein loss. As the thaw occurs, the hypotonic tumor cell surroundings cause the cells to lyse.
  • Interest in cryotherapy has been renewed owing to transrectal ultrasonographic monitoring of the prostate and improved percutaneous probes. Third-generation, gas-driven probes are smaller, allow for better conformal treatment of the gland, and offer the ability of heating, thus accelerating the thaw process and reducing operative time. In addition, by using these argon gas–driven probes, the freezing process can be turned on and off very rapidly, allowing precise extension of the ice ball.
  • Currently, cryotherapy is an outpatient procedure performed with the patient in the lithotomy position. The cryoprobes are inserted through the perineum under transrectal ultrasonographic guidance. The bladder is filled with warm saline. A urethral warmer that keeps the urethra protected from the low temperatures in the surrounding gland is placed into the bladder. In essence, the procedure is very similar to high dose rate brachytherapy.
  • Complications include tissue sloughing, perineal ecchymosis, stricture or contracture, incontinence, impotence (in >90%), and, rarely (in previously nonirradiated disease), fistula formation between the urinary and gastrointestinal tracts. In multicenter studies, 75% of patients had PSA levels of greater than 0.4 ng/mL 12 months after primary treatment (no previous prostate radiation). The complications reported included tissue sloughing in 5%, pad use in 3%, urge symptoms in 5%, and rectal discomfort in 2.6%.
  • Several studies have examined the results of cryotherapy in the treatment of locally recurrent prostate cancer following radiation. This salvage cryotherapy has shown promising results. In 1999, Pisters et al sought to identify a patient population that would benefit from the use of salvage cryosurgery.² In this study, 145 patients were involved; all had locally recurrent adenocarcinomas of the prostate and 108 had received previous radiation treatment. Patients with presalvage cryotherapy PSA levels of less than 10 ng/mL and a history of radiotherapy had an actuarial disease-free 2-year survival rate of 74%. Patients in whom initial radiotherapy failed who had a PSA level greater than 10 ng/mL and a Gleason score greater than 9 were unlikely to be salvaged. However, this study had a short follow-up and no way to distinguish patients who were cured from patients who may have experienced delayed treatment failure.
  • Based on this and other studies, the US Medicare program has begun reimbursing for both primary and salvage cryotherapy for prostate cancer, but the latter only in selected clinical situations.
  • In a 1999 study from the same institution as the Pisters et al study and using patients with similar characteristics, Perrotte et al observed the following complications: incontinence (72%), sloughing (10%), impotence (59%), perineal pain (44%), and bowel symptoms (24%).³
• High-intensity focused ultrasound
• • High-intensity focused ultrasound (HIFU) is an acoustic ablation technique that uses ultrasound waves to destroy prostate tissue. Like cryotherapy, this is a transperineal procedure that does not involve ionizing energy (radiation). 
  • A multicenter national trial is currently comparing the effectiveness of cryotherapy with HIFU.
  • HIFU has been available since 1993 in Canada, Europe, and Mexico but is not yet FDA-approved for use in the United States. Patients who undergo the procedure require a catheter for about 10 days after therapy. While US urologists perform the procedure in Mexico and the Dominican Republic, patients should be counseled that the cure rates with this technique have not been proven.

Locally advanced disease (T3-4N0M0)

• Watchful waiting: Because of the aggressive nature of these tumors, watchful waiting is an option only in highly selected patients with life expectancies of less than 5 years.
• External beam radiotherapy: Treat patients as described above in External beam radiation therapy.
• Brachytherapy: If brachytherapy is used, it is often combined with external beam and hormonal therapy.

MEDICATION

Section 7 of 15  

• Authors and Editors
• Introduction
• Relevant Anatomy
• Histologic Findings and the Tumor Node Metastases (TNM) Staging System
• Treatment
• Nonsurgical Therapy
• Medication
• Surgical Therapy
• Follow-up
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Multimedia
• References

Drug Category: Luteinizing Hormone-releasing Hormone Analog

These agents reduce synthesis of steroid hormones by inhibiting the release of gonadotropin-releasing hormones (GnRHs).

Drug Category: Androgen antagonists

These agents inhibit androgen action through competitive inhibition.

SURGICAL THERAPY

Section 8 of 15  

• Authors and Editors
• Introduction
• Relevant Anatomy
• Histologic Findings and the Tumor Node Metastases (TNM) Staging System
• Treatment
• Nonsurgical Therapy
• Medication
• Surgical Therapy
• Follow-up
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Multimedia
• References

The goal is disease-free survival if the cancer is localized. The goal is symptom-free survival if the cancer has spread outside the confines of the prostatic capsule.

Early localized disease (T1-2N0M0)

Radical prostatectomy involves removal of the prostate and seminal vesicles. Pelvic lymphadenectomy includes the medial half of the external iliac and obturator fossa from the bifurcation of the internal and external iliacs to the node of Cloquet. Currently, 3 approaches are used to remove the prostate gland.

• Radical retropubic prostatectomy: See Prostate Cancer: Radical Retropubic Prostatectomy. This can be performed using either an open or laparoscopic technique. The laparoscopic technique can be performed with robotic assistance.
• Radical perineal prostatectomy: See Prostate Cancer: Radical Perineal Prostatectomy. Advantages include less discomfort, quicker return of bowel function, and shorter hospitalization. Disadvantages include specialized instruments, lack of node sampling or node sampling performed on a separate date, and, in some studies, higher fecal incontinence rates.
• Nonrobotic laparoscopic prostatectomy: Early data from Europe show a steep learning curve. However, once this curve is overcome, early data on intraoperative and postoperative complications appear to be similar to those of open prostatectomy. Although the follow-up was short (<5 y), cancer control appeared equal to that of the open procedure. The long-term rates of continence, anastomotic stricture, and sexual function remain to be determined in larger studies with longer follow-up. Head-to-head outcome studies are currently in progress.
• Robotic-assisted laparoscopic prostatectomy has supplanted pure laparoscopic prostatectomy. At high-volume centers, outcomes appear to be similar to those of open prostatectomy. Proponents of the technique suggest that the magnification offered by the laparoscope and the multiple degrees of freedom will eventually improve potency and continence outcomes. Head-to-head outcome studies are currently ongoing.

The following criteria are general suggestions for any candidate for radical prostatectomy. However, regardless of the approach, the many exceptions and treatment choices must be individualized to each patient's specific situation.

• Patient younger than 75 years
• Few comorbidities, with life expectancy longer than 10 years
• Histologically, Gleason score of 7 or less
• PSA level less than 20 ng/mL

The nomograms mentioned above (see Prostate Nomogram) that combine clinical stage, Gleason score after biopsy, serum PSA level, and other parameters can be used to predict the probability of lymph node involvement. Generally, because the false-negative rate of frozen section analysis of lymph nodes is approximately 3%, patients with a less than 3% projected chance of harboring metastatic prostate cancer in their lymph nodes can safely avoid pelvic lymphadenectomy. At the very least, these patients can avoid having samples of their lymph nodes sent for frozen section analysis in the operating room.

Patients with tumors with higher Gleason scores and PSA levels require a lymph node dissection and frozen section analysis in the operating room only if the surgery is aborted in the context of positive findings. However, series from the Mayo Clinic have shown that continuing with the radical prostatectomy and subsequent antigen deprivation even in the face of cancer-positive nodes has resulted in good long-term survival.

Complications from radical prostatectomy vary widely. This variation depends on the surgeon and center, with high-volume centers generally having superior outcomes. Complications may include impotence, urinary incontinence, strictures, and, possibly, fecal incontinence. Potency rates in previously potent patients vary greatly (5-80%) and depend on patient age and whether a nerve-sparing surgery (unilateral or bilateral) is performed or whether a non–nerve-sparing surgery is performed. Incontinence (4-30%) also depends on the patient's age and whether the surgery is nerve sparing or non–nerve sparing. Strictures (10%) and, rarely, fecal incontinence occur; the latter may occur more commonly with perineal prostatectomy.

Locally advanced disease (T3-4N0M0)

Radical prostatectomy is only occasionally indicated for patients who have undergone a high level of selection and long-term neoadjuvant androgen ablation. The benefit of long-term (ie, >6 mo) neoadjuvant androgen ablation prior to surgery is currently being studied in clinical trials.

FOLLOW-UP

Section 9 of 15  

• Authors and Editors
• Introduction
• Relevant Anatomy
• Histologic Findings and the Tumor Node Metastases (TNM) Staging System
• Treatment
• Nonsurgical Therapy
• Medication
• Surgical Therapy
• Follow-up
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Multimedia
• References

Follow-up is not standardized; however, practitioners use general guidelines that are mainly derived from publications that report outcomes on various methods of treatment. In addition, the National Comprehensive Cancer Network, an alliance of 19 cancer centers, publishes follow-up guidelines for the various treatment modalities discussed below.

• Watchful waiting and androgen ablation
• • A DRE and PSA test are performed every 3-12 months.
  • Although not unanimous, many experts believe that treating patients for metastatic disease with androgen ablation before they become symptomatic offers the potential for increased survival. Hence, bone scans are performed yearly in many patients. An alternative approach has been to perform yearly bone scans once the serum PSA level exceeds 40 ng/mL, which is associated with a significant probability of positive bone scan results.
  • Some have recommended biopsy of the prostate at 18-24 months to determine if the grade of the cancer has changed. If such a grade change occurs, some physicians and patients may consider more definitive therapy.
• Radical prostatectomy
• • DRE has not been shown to offer any added advantage in the detection of local recurrence beyond PSA testing; hence, it is not routinely performed.
  • PSA testing is performed every 3-4 months for the first 2 years, every 6 months for the third and fourth years, and yearly thereafter.
• External beam radiotherapy
• • DRE and PSA are performed every 3-6 months for 5 years, then annually thereafter.
  • Some practitioners perform biopsy of the prostate at 18-24 months following treatment.
• Brachytherapy
• • PSA testing is performed every 3-6 months for 1 year, then annually thereafter.
  • Some practitioners perform biopsy of the prostate at 18-24 months following treatment.
• Biochemical recurrence
• • A biochemical recurrence (ie, measurable PSA) is considered to have occurred following radical prostatectomy if the PSA level is greater than 0.2 ng/mL or greater than the minimal detectable level of the assay. For example, using the ultrasensitive PSA assays, a cutoff of 0.01 ng/mL or 0.05 ng/mL can be used.
  • The definition of a biochemical recurrence following radiation is more complex, and significant debate still surrounds this topic. Three options for determining biochemical recurrence include (1) 2-3 consecutive rises in the PSA level following a nadir; (2) 3 consecutive rises in the PSA level regardless of the nadir; and (3) an absolute cutoff of 0.2, 0.5, or 1 ng/mL.
  • Biochemical recurrence should prompt closer follow-up and consideration of alternate therapies. When the PSA level begins doubling every 10-12 months or reaches a level of 20 ng/mL, imaging studies may be performed.
  • • Bone scan
    • Chest radiography
    • CT scanning of the abdomen and pelvis
    • Potentially, transrectal ultrasound–guided rebiopsy of the prostate or prostatic fossa in patients treated with radical prostatectomy
    • ProstaScint scan (Cytogen; Princeton, NJ), ie, capromab pendetide scan: The basis for this nuclear scan is prostate-specific membrane antigen, a glycoprotein restricted to the prostate whose level is elevated in men with prostate cancer. Prostate-specific membrane antigen is conjugated to the CYT-356 antibody and is used in immunoscintigraphy. This antibody is labeled with indium (In)–111 and is used to detect extraprostatic spread. Most commonly, it is used in patients who have biochemical recurrence but who are candidates for additional external beam radiotherapy. The ProstaScint scan is especially useful for identifying localized recurrence and lymphatic spread.
    • Positron emission tomography scan: This is an imaging study that uses cancer metabolism to illuminate cancer spread to other organs.
    • MRI spectroscopy: This study combines anatomic information with metabolic activity to detect residual cancer in the gland.
• Salvage therapy
• • Patients who have PSA (biochemical) failure following radical prostatectomy and have no evidence of metastatic disease have the options of watchful waiting, radiotherapy, or hormonal ablation as salvage therapy. The choice of therapy depends on the timing of the recurrence (ie, soon after surgery) and the rate of PSA level elevation.
  • Similarly, patients who have PSA failure following radiation therapy have the options of watchful waiting, brachytherapy, prostatectomy, cystoprostatectomy, cryotherapy, and hormonal ablation.
  • Newer concepts in treatment include intermittent hormone therapy and sequential blockade. Intermittent hormone therapy refers to cycles on androgen ablation and cycles off androgen ablation to keep the PSA level low and to minimize the adverse physical effects of androgen blockade.
  • The use of docetaxel (Taxotere) as a chemotherapeutic agent has been effective in metastatic hormone-refractory prostate cancer. Studies evaluating the role of Taxotere earlier in the disease course are ongoing.

For excellent patient education resources, visit eMedicine's Prostate Health Center and Cancer and Tumors Center. Also, see eMedicine's patient education article Prostate Cancer.

COMPLICATIONS

Section 10 of 15  

• Authors and Editors
• Introduction
• Relevant Anatomy
• Histologic Findings and the Tumor Node Metastases (TNM) Staging System
• Treatment
• Nonsurgical Therapy
• Medication
• Surgical Therapy
• Follow-up
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Multimedia
• References

Emergent Care

Urinary retention

This may be secondary to urethral strictures, bladder outlet obstruction, or a blood clot. Attempt placement of a 20-24F Foley catheter. The catheter should go into the hub before any fluid is placed into the balloon port. If this is at all difficult, do not force insertion of the catheter. Strictures require dilatation by a urologist.

Long-term urinary retention or malignant urinary obstruction due to untreated prostate cancer can lead to chronic renal failure, which manifests as uremic symptoms and an elevated serum creatinine level. Patients on watchful waiting protocols are at risk for this if they are not closely monitored.

Hematuria

This may manifest as a small element of prostate venous bleeding or it may lead to large clots. Hematuria is more common in patients who have undergone radiation therapy.

Vigorously irrigate blood clots with copious amounts of fluid to remove all evidence of clots. Sterile water is best because it helps to lyse the clot. However, use care because absorption of the fluid may occur in situations in which prostatic venous channels are open.

Incontinence due to bladder spasm or irritation is common immediately after various prostate treatments. While patients have urinary catheters, oxybutynin, tolterodine, belladonna and opium suppositories, and phenazopyridine (Pyridium) may be used to decrease symptoms.

Although uncommon, a urethrorectal fistula may occur after surgery or radiation. Manage the fistula with urinary and fecal diversion using appropriate protocols and services.

Rectal bleeding and tenesmus are observed in patients treated with radiation.

Bone pain due to metastatic disease requires narcotics, awareness of fractures, and, possibly, palliative radiation. These lesions tend to be blastic as well as lytic.

Treatment of complications

Prostatic bleeding may be treated with androgen ablation, ketoconazole, aminocaproic acid (Amicar), diethylstilbestrol (Stilphostrol), and bisphosphonates.

Bone pain due to metastatic disease requires narcotics, awareness of fractures, and, possibly, palliative radiation or strontium therapy.

Ureteral obstruction due to lymphadenopathy may be treated with a ureteral stent or percutaneous nephrostomy.

OUTCOME AND PROGNOSIS

Section 11 of 15  

• Authors and Editors
• Introduction
• Relevant Anatomy
• Histologic Findings and the Tumor Node Metastases (TNM) Staging System
• Treatment
• Nonsurgical Therapy
• Medication
• Surgical Therapy
• Follow-up
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Multimedia
• References

Disease-specific survival for early localized disease at 10 years

The ranges of the disease-free 10-year survival rates for early localized disease listed below are wide because the outcomes of these treatments vary as a function of tumor aggressiveness (ie, based on Gleason score and PSA level). In addition, series from various institutions show significant differences.

• Radical prostatectomy (80-95%)
• Brachytherapy and external radiation (80-95%)
• Watchful waiting (50-73%)

Disease-specific survival for advanced localized disease at 10 years

The disease-specific 10-year survival rate for advanced localized disease in patients treated with brachytherapy and external radiation is 40-62%. Holmberg et al found improved disease-specific survival in patients treated with surgery compared with watchful waiting (4.6% vs 8.9%).⁴

FUTURE AND CONTROVERSIES

Section 12 of 15  

• Authors and Editors
• Introduction
• Relevant Anatomy
• Histologic Findings and the Tumor Node Metastases (TNM) Staging System
• Treatment
• Nonsurgical Therapy
• Medication
• Surgical Therapy
• Follow-up
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Multimedia
• References

Survival benefits when comparing the different modalities used for treating localized prostate cancer remain controversial. In the future, the measurement of bound and free PSA will help discriminate between more aggressive and less aggressive cancers.

Molecular prognostic markers

Over the past few years, research has shown that several molecular markers aid in the prognostication of patients undergoing treatment for localized and metastatic prostate cancers. Researchers report on the assessment of the molecular alterations or gene products of TP53, RB, BCL2, cathepsin-D, CDH1, and PTEN, among many others. Prospective trials are needed to assess these markers more thoroughly before their implementation in current patient management is recommended.

Reverse transcriptase-polymerase chain reaction

Reverse transcriptase-polymerase chain reaction (RT-PCR) testing may be able to identify very small amounts of PSA nucleic acid in the blood stream, prostatic fossa, or bone marrow. In the future, RT-PCR may be helpful for determining which patients have residual tumor following surgery (eg, RT-PCR–positive prostate fossa) or higher rates of tumor recurrence (eg, RT-PCR–positive lymph nodes at surgery, persistently positive bone marrow samples months after treatment).

Gene therapy

Treatment options may include corrective gene therapy (ie, replacing a normal tumor suppressor gene in tumors with a mutated one) or toxic gene therapy to destroy cancer cells. Clinical trials using prostate-specific adenovirus, which expresses a gene toxic to prostate cancer cells, currently are underway in several centers worldwide. Other options include tumor vaccines or vaccination with tumor- or prostate-specific proteins such as PSA.

Other treatments

• Vitamin D analogs
• Antiangiogenesis agents
• Antimetastatic agents that slow cancer progression
• Radiation sensitizers: These may be used to increase the sensitivity of cancer cells to cell death by radiation. These may include photosensitizers or chemotherapeutic agents coupled with radiation.

FURTHER READING

Section 13 of 15  

• Authors and Editors
• Introduction
• Relevant Anatomy
• Histologic Findings and the Tumor Node Metastases (TNM) Staging System
• Treatment
• Nonsurgical Therapy
• Medication
• Surgical Therapy
• Follow-up
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Multimedia
• References

For more information, visit Medscape’s Prostate Cancer Resource Center.

MULTIMEDIA

Section 14 of 15  

• Authors and Editors
• Introduction
• Relevant Anatomy
• Histologic Findings and the Tumor Node Metastases (TNM) Staging System
• Treatment
• Nonsurgical Therapy
• Medication
• Surgical Therapy
• Follow-up
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Multimedia
• References

Media file 1:  Management of localized prostate cancer. This diagram depicts the relevant anatomy of the male pelvis and genitourinary tract.
	View Full Size Image
Media type:  Image

Media file 2:  Management of localized prostate cancer. This photo illustrates the histologic scoring system (Gleason score) derived from the two most common patterns seen on the biopsy specimen.
	View Full Size Image
Media type:  Photo

REFERENCES

Section 15 of 15

• Authors and Editors
• Introduction
• Relevant Anatomy
• Histologic Findings and the Tumor Node Metastases (TNM) Staging System
• Treatment
• Nonsurgical Therapy
• Medication
• Surgical Therapy
• Follow-up
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Multimedia
• References

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