Prostate Cancer Treatment (PDQ®) 5/7 —Health Professional Version - National Cancer Institute

Prostate Cancer Treatment (PDQ®)—Health Professional Version - National Cancer Institute

Prostate Cancer Treatment (PDQ®)–Health Professional Version

Stage II Prostate Cancer Treatment

In This Section

• Overview
  • Prostate-specific antigen (PSA) changes as markers of tumor progression
  • Bisphosphonates and risk of bone metastases
• Standard Treatment Options for Stage II Prostate Cancer
  • Watchful waiting or active surveillance/active monitoring
  • Radical prostatectomy
  • External-beam radiation therapy (EBRT) with or without hormonal therapy
  • Interstitial implantation of radioisotopes
• Treatment Options Under Clinical Evaluation for Stage II Prostate Cancer
  • Ultrasound-guided percutaneous cryosurgery
  • High-intensity focused ultrasound
  • Proton-beam radiation therapy
  • Photodynamic therapy
  • Other clinical trials
• Current Clinical Trials

Overview

Stage II prostate cancer is defined by the American Joint Committee on Cancer's TNM (tumor, node, metastasis) classification system:[1]

Stage IIA

• cT1a–c, N0, M0, prostate-specific antigen (PSA) ≥10 <20 ng/mL, Gleason ≤6.
• cT2a, N0, M0, PSA ≥10 <20 ng/mL, Gleason ≤6.
• pT2, N0, M0, PSA ≥10 <20 ng/mL, Gleason ≤6.
• cT2b–c, N0, M0, PSA <20 ng/mL, Gleason ≤6.

Stage IIB

• T1–2, N0, M0, PSA <20 ng/mL, Gleason 7.

Stage IIC

• T1–2, N0, M0, PSA <20, Gleason 7 or 8.

Radical prostatectomy, external-beam radiation therapy (EBRT), and interstitial implantation of radioisotopes are each employed in the treatment of stage II prostate cancer with apparently similar therapeutic effects. Radical prostatectomy and radiation therapy yield apparently similar survival rates with as many as 10 years of follow-up. For well-selected patients, radical prostatectomy is associated with a 15-year survival comparable with an age-matched population without prostate cancer.[2] Unfortunately, randomized comparative trials of these treatment methods with prolonged follow-up are lacking.

Patients with a small, palpable cancer (T2a, N0, and M0) fare better than patients in whom the disease involves both sides of the gland (T2c, N0, and M0). Patients proven free of node metastases by pelvic lymphadenectomy fare better than patients in whom this staging procedure is not performed; however, this is the result of selection of patients who have a more favorable prognosis.

Side effects of the various forms of therapy—including impotence, incontinence, and bowel injury—should be considered in determining the type of treatment to employ.

Prostate-specific antigen (PSA) changes as markers of tumor progression

Often, changes in PSA are thought to be markers of tumor progression. Even though a tumor marker or characteristic may be consistently associated with a high risk of prostate cancer progression or death, it may be a very poor predictor of very limited utility in making therapeutic decisions.

Baseline PSA and rate of PSA change were associated with subsequent metastasis or prostate cancer death in a cohort of 267 men with clinically localized prostate cancer who were managed by watchful waiting or active surveillance in the control arm of a randomized trial comparing radical prostatectomy with watchful waiting.[3,4] Nevertheless, the accuracy of classifying men into groups whose cancer remained indolent versus those whose cancer progressed was poor at all examined cut points of PSA or PSA rate of change.

Bisphosphonates and risk of bone metastases

Patients with locally advanced nonmetastatic disease (T2–T4, N0–N1, and M0) are at risk for developing bone metastases. Bisphosphonates are being studied as a strategy to decrease this risk.

Evidence (bisphosphonates and risk of bone metastases):

1. A placebo-controlled randomized trial (MRC-PR04) of a 5-year regimen of the first-generation bisphosphonate clodronate in high oral doses (2,080 mg qd) had no favorable impact on either time to symptomatic bone metastasis or survival.[5][Level of evidence: 1iA]

Standard Treatment Options for Stage II Prostate Cancer

Standard treatment options for patients with stage II prostate cancer include the following:

1. Watchful waiting or active surveillance/active monitoring.
2. Radical prostatectomy.
3. External-beam radiation therapy (EBRT) with or without hormonal therapy.
   • 3-dimensional (3D) conformal radiation therapy.
4. Interstitial implantation of radioisotopes.

Watchful waiting or active surveillance/active monitoring

Asymptomatic patients of advanced age or with concomitant illness may warrant consideration of careful observation without immediate active treatment.[6-8] Watch and wait, observation, expectant management, and active surveillance/active monitoring are terms indicating a strategy that does not employ immediate therapy with curative intent. (Refer to the Treatment Option Overview for Prostate Cancer section of this summary for more information).

Evidence (observation with delayed hormonal therapy):

1. In a retrospective pooled analysis, 828 men with clinically localized prostate cancer were managed by initial conservative therapy with subsequent hormonal therapy given at the time of symptomatic disease progression.[6]
   • This study showed that the patients with well-differentiated tumors or moderately well-differentiated tumors experienced a disease-specific survival of 87% at 10 years and that their overall survival (OS) closely approximated the expected survival among men of similar ages in the general population.
   • The decision to treat should be made in the context of the patient’s age, associated medical illnesses, and personal desires.

Radical prostatectomy

Radical prostatectomy, usually with pelvic lymphadenectomy (with or without the nerve-sparing technique designed to preserve potency) is the most commonly applied therapy with curative intent.[2,9,10] Radical prostatectomy may be difficult after a transurethral resection of the prostate (TURP).

Because about 40% to 50% of men with clinically organ-confined disease are found to have pathologic extension beyond the prostate capsule or surgical margins, the role of postprostatectomy adjuvant radiation therapy has been studied.

Consideration may also be given to postoperative radiation therapy (PORT) for patients who are found to have seminal vesicle invasion by tumor at the time of prostatectomy or who have a detectable level of PSA more than 3 weeks after surgery.[11-13] Because the duration of follow-up in available studies is relatively short, the value of PORT is yet to be determined; however, PORT does reduce local recurrence.[11] Careful treatment planning is necessary to avoid morbidity.

Evidence (radical prostatectomy followed by radiation therapy):

1. In a randomized trial of 425 men with pathologic T3, N0, M0 disease, postsurgical EBRT (60–64 Gy to the prostatic fossa over 30–32 fractions) was compared with observation.[12][Level of evidence: 1iiA]
   • The primary endpoint, metastasis-free survival, could be affected by serial PSA monitoring and resulting metastatic work-up for PSA increase. This could have biased the primary endpoint in favor of radiation therapy, which was associated with a lower rate of PSA rise. Nevertheless, metastasis-free survival was not statistically different between the two study arms (P = .06). After a median follow-up of about 10.6 years, overall median survival was 14.7 years in the radiation therapy group versus 13.8 years in the observation group (P = .16).
   • Although the OS rates were not statistically different, complication rates were substantially higher in the radiation therapy group compared with the observation group: overall complications were 23.8% versus 11.9%, rectal complications were 3.3% versus 0%, and urethral stricture was 17.8% versus 9.5%, respectively.
   • After a median follow-up of about 12.5 years, however, OS was better in the radiation therapy arm; hazard ratio (HR)death, 0.72 (95% confidence interval [CI], 0.55–0.96; P = .023). The 10-year estimated survival rates were 74% in the radiation therapy arm and 66% in the control arm. The 10-year estimated metastasis-free survivals were 73% and 65% (P = .016).[13][Level of evidence: 1iiA]

Evidence (radical prostatectomy compared directly with watchful waiting/active surveillance/active monitoring and/or external-beam radiation therapy):

1. In a randomized clinical trial performed in Sweden in the pre-PSA screening era, 695 men with prostate cancer were randomly assigned to radical prostatectomy versus watchful waiting. Only about 5% of the men in the trial had been diagnosed by PSA screening. Therefore, the men had more extensive local disease than is typically the case in men diagnosed with prostate cancer in the United States.[14-16]
   • The cumulative overall mortality at 18 years was 56.1% in the radical prostatectomy arm and 68.9% in the watchful waiting study arm (absolute difference, 12.7%; 95% CI, 5.1–20.3 percentage points; relative risk [RR]death,0.71; 95% CI, 0.59–0.86.[16][Level of evidence: 1iiA]
   • The cumulative incidence of prostate cancer deaths at 18 years was 17.7% versus 28.7% (absolute difference, 11.0%; 95% CI, 4.5–17.5 percentage points; RRdeath from prostate cancer, 0.56; 95% CI, 0.41–0.77).[16]
   • In a post-hoc–subset analysis, the improvement in overall and prostate cancer-specific mortality associated with radical prostatectomy was restricted to men younger than 65 years.
2. The Prostate Intervention Versus Observation Trial (PIVOT-1 or VA-CSP-407) is a randomized trial conducted in the PSA screening era that directly compared radical prostatectomy with watchful waiting. From November 1994 through January 2002, 731 men aged 75 years or younger with localized prostate cancer (stage T1–2, NX, M0, with a blood PSA <50 ng/mL) and a life expectancy of at least 10 years were randomly assigned to radical prostatectomy versus watchful waiting.[17-19][Levels of evidence: 1iiA, 1iiB]
   • About 50% of the men had palpable tumors.
   • After a median follow-up of 12.7 years (range up to about 19.5 years), the all-cause mortality was 61.3% versus 66.8% in the radical-prostatectomy and watchful-waiting study arms, respectively, an absolute difference of 5.5 percentage points (95% CI -1.5 to 12.4) that was not statistically significant (HR, 0.84; 95% CI, 0.70–1.01). Prostate cancer–specific mortality was 7.4% versus 11.4%, and it also was not statistically significant (HR, 0.63; 95% CI, 0.3–1.02).
   • Although treatment for disease progression was given more frequently in the observation arm of the study, most such treatment was for asymptomatic, local, or biochemical (PSA) progression.
   • As expected, urinary incontinence and erectile/sexual dysfunction was more common in the prostatectomy group for at least 10 years of follow-up. Absolute differences in patient-reported use of absorbent urinary pads was greater in the surgery group by more than 30 percentage points at all time points for at least 10 years. Disease- or treatment-related limitations in activities of daily living were worse with surgery than with observation through 2 years, but then were similar in both study arms.
3. In the ProtecT trial (NCT02044172 and ISRCTN20141297), 82,429 men were screened with PSA testing, and 2,664 were diagnosed with clinically localized prostate cancer, of whom 1,643 (median age 62 years, range 50-69 years) consented to a randomly assigned comparison of active monitoring, radical prostatectomy (nerve-sparing when possible), or external-beam 3D conformal radiation (74 Gy in 37 fractions). The primary endpoint was prostate cancer-specific mortality.[20]
   1. With a median follow-up of 10 years, there were a total of 17 deaths from prostate cancer, with no statistically significant differences among the three study arms (P = .48). The 10-year prostate cancer–specific survival rates were 98.8% in the active monitoring arm, 99.0% in the radical prostatectomy arm, and 99.6% radiation therapy arms.[20][Level of evidence: 1iiA]
   2. Likewise, all-cause mortality was nearly identical in all three study arms: 10.9 deaths in the active monitoring arm, 10.1 in the radical prostatectomy arm, and 10.3 in the radiation therapy arm per 1,000 person-years (P = .87).[20][Level of evidence: 1iiA]
   3. There were statistically significant differences in progression to metastatic disease among the treatment arms (active monitoring, 33/545; radical prostatectomy, 13/553; radiation therapy, 16/545) that began to emerge after 4 years, but these differences had not translated into any difference in mortality by the 10-year follow-up. Over the course of 10 years, 52% of the patients required active intervention.
   4. As expected, there were substantial differences in patient-reported outcomes among the three management approaches.[21][Level of evidence: 1iiC] A substudy of patient-reported outcomes up to 6 years after randomization included the following:
      • Men in the radical prostatectomy study arm had substantial rates of urinary incontinence (e.g., using one or more absorbent pads qd was reported by 46% at 6 months and by 17% at year 6) with very little incontinence in the other two study arms.
      • Sexual function was also worse in the radical prostatectomy group (e.g., at 6 months, 12% of men reported erections firm enough for intercourse vs. 22% in the radiation therapy arm and 52% in the active-monitoring arm).
      • Bowel function, however, was worse in the radiation therapy arm (e.g., about 5% reported bloody stools at least half the time at 2 years and beyond versus none in the radical prostatectomy and active-monitoring study arms).

External-beam radiation therapy (EBRT) with or without hormonal therapy

EBRT is another treatment option often used with curative intent.[22-26] Definitive radiation therapy should be delayed 4 to 6 weeks after TURP to reduce the incidence of stricture.[27] Adjuvant hormonal therapy should be considered for patients with bulky T2b to T2c tumors.[28]

The role of adjuvant hormonal therapy in patients with locally advanced disease has been analyzed by the Agency for Health Care Policy and Research (now the Agency for Healthcare Research and Quality). Most patients had more advanced disease, but patients with bulky T2b to T2c tumors were included in the studies that were re-evaluating the role of adjuvant hormonal therapy in patients with locally advanced disease.

Evidence (EBRT with or without adjuvant hormonal therapy):

1. The Radiation Therapy Oncology Group's (RTOG) trial 7706 (RTOG-7706).[29][Level of evidence: 1iiA]
   • Prophylactic radiation therapy to clinically or pathologically uninvolved pelvic lymph nodes does not appear to improve OS or prostate cancer-specific survival.
2. RTOG-9413 (RTOG-9413 [NCT00769548]) trial.[30,31][Level of evidence: 1iiDiii]
   • Although RTOG-9413 showed increased progression-free survival at 4 years for patients who had a 15% estimated risk of lymph node involvement and received whole-pelvic radiation therapy compared with prostate-only radiation therapy, OS and PSA failure rates were not significantly different.
3. In a randomized trial, 875 men with locally advanced nonmetastatic prostate cancer (T1b–T2 moderately or poorly differentiated tumors; T3 tumors of any grade) were randomly assigned to receive 3 months of a luteinizing hormone-releasing hormone (LH-RH) agonist plus long-term flutamide (250 mg PO tid) with or without EBRT.[32][Level of evidence 1iiA]
   • Nineteen percent of the men had tumor stage T2, and 78% of the men had tumor stage T3. At 10 years, both overall mortality (29.6% vs. 39.4%; 95% CI for the difference, 0.8%–18.8%) and prostate cancer-specific mortality (11.9% vs. 23.9%; 95% CI for the difference, 4.9%–19.1%) favored combined hormonal and radiation therapy.
   • Although flutamide might not be considered a standard hormonal monotherapy in the setting of T2 or T3 tumors, radiation therapy provided a disease-free survival or tumor-specific survival advantage even though this monotherapy was applied. This analysis rests on the assumption that flutamide does not shorten life expectancy and cancer-specific survival. Radiation therapy was not delivered by current standards of dose and technique.
4. Another trial compared androgen deprivation therapy (ADT: an LH-RH agonist or orchiectomy) with ADT plus radiation therapy (65–69 Gy to the prostate by 4-field box technique, including 45 Gy to the whole pelvis, seminal vesicles, and external/internal iliac nodes unless the lymph nodes were known to be histologically negative). This trial, NCIC CTG PR.3/MRC UKPRO7 [NCT00002633], from the National Cancer Institute of Canada randomly assigned 1,205 patients with high-risk (PSA >40 ng/mL or PSA >20 ng/mL and Gleason score ≥8), T2 (12%–13% of the patients), T3 (83% of the patients), and T4 (4%–5% of the patients) with clinical or pathologically staged N0, M0 disease.[33,34][Level of evidence; 1iiA]
   • At a median follow-up of 8 years (maximum = 13 years), OS was superior in the ADT-plus-radiation therapy group (HRdeath, 0.77; 95% CI, 0.57–0.85, P = .001). OS at 10 years was 55% for the ADT-plus-radiation therapy group versus 49% for the ADT-alone group.
   • Although radiation therapy had the expected bowel and urinary side effects, quality of life was the same in each study group by 24 months and beyond.[35]
5. A meta-analysis of randomized clinical trial evidence comparing radiation therapy with radiation therapy plus prolonged androgen suppression has been published. The meta-analysis found a difference in 5-year OS in favor of radiation therapy plus continued androgen suppression (LH-RH agonist or orchiectomy) as compared with radiation therapy alone (HR, 0.631; 95% CI, 0.479–0.831).[28][Level of evidence: 1iiA]
6. A meta-analysis of seven randomized controlled trials comparing early hormonal treatment (adjuvant or neoadjuvant) to deferred hormonal treatment (LH-RH agonists and/or antiandrogens) in patients with locally advanced prostate cancer, whether treated with prostatectomy, radiation therapy, or watchful waiting or active surveillance/active monitoring, showed improved overall mortality for patients receiving early treatment (RR, 0.86; 95% CI, 0.82–0.91).[36][Level of evidence: 1iiA]
7. Short-term neoadjuvant-androgen therapy administered before and during radiation therapy has shown benefit in at least some patients with clinically localized prostate cancer. In an open-label, randomized trial (RTOG-9408 [NCT00002597]), 1,979 men with nonmetastatic stage T1b–c, T2a, or T2b tumors and a PSA level of 20 ng/mL or less were randomly assigned to receive radiation therapy (66.6 Gy prostate dose in 1.8 Gy daily fractions ) with or without 4 months of ADT (flutamide 250 mg PO tid plus either monthly goserelin 3.6 mg subcutaneously (SQ) or leuprolide 7.5 mg intramuscularly), beginning 2 months before radiation therapy. Median follow-up was about 9 years.[37][Level of evidence: 1iiA]
   • The 10-year OS rate was 57% in the radiation-only group versus 62% in the combined-therapy group (HRdeath, 1.17; 95% CI, 1.01–1.35; P = .03).
   • In a post-hoc analysis, there was no statistically significant interaction between the treatment effect and baseline-risk category of the patients. However, there appeared to be little, if any, benefit associated with combined therapy in the lowest-risk category of patients (Gleason score ≤6; PSA ≤10 ng/mL; and clinical stage ≤T2a).
   • The OS benefit was most apparent in men with intermediate-risk tumors (Gleason score 7; or Gleason score ≤6 and PSA >10 ng/mL; or clinical stage T2b).
8. The duration of neoadjuvant hormonal therapy has been tested in a randomized trial (TROG 96.01 [ACTRN12607000237482]) involving 818 men with locally advanced (T2b, T2c, T3, and T4) nonmetastatic cancer treated with radiation therapy (i.e., 66 Gy in 2 Gy daily fractions to the prostate and seminal vesicles but not including regional lymph nodes).[38] In an open-label design, patients were randomly assigned to radiation therapy alone, 3 months of neoadjuvant androgen deprivation therapy (NADT) (goserelin 3.6 mg SQ each month plus flutamide 250 mg PO tid) for 2 months before and during radiation, or 6 months of NADT for 5 months before and during radiation.[38][Level of evidence: 1iiA]
   • After a median follow-up of 10.6 years, there were no statistically significant differences between the radiation-alone group and the radiation-plus-3-months-of NADT group.
   • However, the 6-month NADT arm showed better prostate–cancer-specific mortality and overall mortality than the radiation-alone group; 10-year all-cause mortality 29.2% versus 42.5% (HR, 0.63; 95% CI, 0.48–0.83, P = .0008).
9. The duration of neoadjuvant hormonal therapy was tested in another trial (RTOG-9910 [NCT00005044]) of 1,489 eligible men with intermediate-risk prostate cancer (T1b–4, Gleason score 2–6, and PSA >10 but ≤100 ng/mL; T1b–4, Gleason score 7, and PSA <20; or T1b–1c, Gleason score 8–10, and PSA <20) and no evidence of metastases. The men were randomly assigned to receive short-course neoadjuvant–androgen suppression (an LHRH agonist plus bicalutamide or flutamide for 8 weeks before and 8 weeks during radiation therapy) or long-course neoadjuvant–androgen suppression (28 weeks before and 8 weeks during radiation therapy). Both groups received 70.2 Gy radiation in 39 daily fractions to the prostate and 46.8 Gy to the iliac lymph nodes.[39][Levels of evidence: 1iiA and 1iiB]
   • After a median of 9.4 years, 10-year prostate-specific mortality, the primary endpoint, was low in both study arms: 5% versus 4% (HR, 0.81; 95% CI, 0.48–1.39).[39][Level of evidence: 1iiB]
   • No statistically significant differences in overall mortality or in locoregional disease progression were found.[39][Level of evidence: 1iiA]
   • There was also no apparent differential effect of androgen suppression duration among any of the risk-group subsets.
10. Addition of androgen suppression therapy to EBRT may benefit men who are at an elevated risk of disease recurrence and death from prostate cancer (RTOG-9202[NCT00767286]).

3-dimensional (3D) conformal radiation therapy

EBRT designed to decrease exposure of normal tissues using methods such as CT-based 3D conformal treatment planning is under clinical evaluation.[40]

Interstitial implantation of radioisotopes

Interstitial implantation of radioisotopes (i.e., iodine I 125 [125I], palladium, and iridium), using a transperineal technique with either ultrasound or computed-tomography (CT) guidance, is being done in patients with T1 or T2a tumors. Short-term results in these patients are similar to those for radical prostatectomy or EBRT.[41,42]; [43][Level of evidence: 3iiiDiv]

Factors for consideration in the use of interstitial implants include the following:

• The implant is performed as outpatient surgery.
• The rate of maintenance of sexual potency with interstitial implants has been reported to be 86% to 92%.[41,43] In contrast, rates of maintenance of sexual potency with radical prostatectomy were 10% to 40% and 40% to 60% with EBRT.
• Typical side effects from interstitial implants that are seen in most patients but subside with time include urinary tract frequency, urgency, and less commonly, urinary retention.
• Rectal ulceration may also be seen.[41] In one series, a 10% 2-year actuarial genitourinary grade 2 complication rate and a 12% risk of rectal ulceration were seen. This risk decreased with increased operator experience and modification of the implant technique.[44]

Long-term follow-up of these patients is necessary to assess treatment efficacy and side effects.

Retropubic freehand implantation with 125I has been associated with an increased local failure and complication rate [44,45] and is now rarely done.

Treatment Options Under Clinical Evaluation for Stage II Prostate Cancer

Treatment options under clinical evaluation for patients with stage II prostate cancerinclude the following:

1. Ultrasound-guided percutaneous cryosurgery.
2. High-intensity focused ultrasound.
3. Proton-beam radiation therapy.
4. Photodynamic therapy.
5. Other clinical trials.

Ultrasound-guided percutaneous cryosurgery

Cryosurgery is a surgical technique that involves destruction of prostate cancer cells by intermittent freezing of the prostate with cryoprobes followed by thawing.[46][Level of evidence: 3iiiC]; [47,48][Level of evidence: 3iiiDiv] Cryosurgery is less well established than standard prostatectomy, and long-term outcomes are not as well established as with prostatectomy or radiation therapy. Serious toxic effects include:

• Bladder outlet injury.
• Urinary incontinence.
• Sexual impotence.
• Rectal injury.

The frequency of other side effects and the probability of cancer control at 5 years' follow-up have varied among reporting centers, and series are small compared with surgery and radiation therapy.[47,48]

High-intensity focused ultrasound

High-intensity focused ultrasound has been reported in case series to produce good local disease control. However, it has not been directly compared with more standard therapies, and experience with it is more limited.[49-51]

Proton-beam radiation therapy

There is growing interest in the use of proton-beam radiation therapy for the treatment of prostate cancer. Although the dose distribution of this form of charged-particle radiation has the potential to improve the therapeutic ratio of prostate radiation, allowing for an increase in dose to the tumor without a substantial increase in side effects, no randomized controlled trials have been that compare its efficacy and toxicity with those of other forms of radiation therapy.

Photodynamic therapy

Vascular-targeted photodynamic therapy using a photosensitizing agent has been tested in men with low-risk prostate cancer. In the CLIN1001 PCM301 (NCT01310894) randomized trial, 413 men with low-risk cancer (tumor stage T1–T2c, PSA ≤10 ng/mL, generally Gleason score 3 + 3) were randomly assigned in an open-label trial to receive either the photosensitizing agent, padeliporfin (4 mg/kg IV over 10 minutes, and optical fibers inserted into the target area of the prostate, then activated by 753 nm laser light at 150 mW/cm for 22 minutes 15 seconds), or active surveillance.[52] Median time to local disease progression was 28.3 months for patients receiving padeliporfin and 14.1 months for patients who were under active surveillance (HR, 0.34; 95% CI, 0.24–0.46; P < .0001).[52][Level of evidence: 1iiDiii] However, the appropriate population for photodynamic therapy may be quite narrow, as it may overtreat men with very low-risk disease and undertreat men with higher-risk disease.[53]

Other clinical trials

Other clinical trials, including trials of neoadjuvant hormonal therapy followed by radical prostatectomy, are ongoing.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

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