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Stage III Prostate Cancer Treatment

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    Watchful waiting or active surveillance

    Careful observation without further immediate treatment may be used in the treatment of stage III prostate cancer.[43,44]

    Asymptomatic patients of advanced age or with concomitant illness may warrant consideration of careful observation without immediate active treatment.[45,46,47] Watch and wait, observation, expectant management, and active surveillance 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.)

    Treatment of Symptoms

    Since many stage III patients have urinary symptoms, control of symptoms is an important consideration in treatment. The following modalities may be used to improve local control of disease and subsequent symptoms:

    • Radiation therapy.
    • Hormonal manipulation.
    • Palliative surgery (transurethral resection of the prostate [TURP]).
    • Interstitial implantation combined with EBRT.
    • Alternative forms of radiation therapy (under clinical evaluation).
    • Ultrasound-guided percutaneous cryosurgery (under clinical evaluation).
    1. Radiation therapy.[3,4,5,6] EBRT designed to decrease exposure of normal tissues using methods such as CT-based 3D-CRT treatment planning is under clinical evaluation.
    2. Hormonal manipulations effectively used as initial therapy for prostate cancer include the following:
      • Orchiectomy.
      • Leuprolide or other LH-RH agonists (e.g., goserelin) in daily or depot preparations. These agents may be associated with tumor flare.
      • Estrogens (diethylstilbestrol [DES] is no longer available in the United States).
      • Nonsteroidal antiandrogens (e.g., flutamide, nilutamide, and bicalutamide) or steroidal antiandrogen (e.g., cyproterone acetate).

      A meta-analysis of randomized trials comparing various hormonal monotherapies in men with stage III or stage IV prostate cancer (predominantly stage IV) came to the following conclusions:[48][Level of evidence: 1iiA]

      • OS at 2 years using any of the LH-RH agonists is similar to treatment with orchiectomy or 3 mg per day of DES (HR, 1.26; 95% CI, 0.92–1.39).
      • Survival rates at 2 years are similar or worse with nonsteroidal antiandrogens compared with orchiectomy (HR, 1.22; 95% CI, 0.99–1.50).
      • Treatment withdrawals, used as a surrogate for adverse effects, occurred less with LH-RH agonists (0%–4%) than with nonsteroidal antiandrogens (4%–10%).
    3. Palliative surgery (TURP).
    4. Interstitial implantation combined with EBRT is being used in selected T3 patients, but little information is available.[49]
    5. Alternative forms of radiation therapy are being employed in clinical trials. A randomized trial from the RTOG reported improved local control and survival with mixed-beam (neutron/photon) radiation therapy compared with standard photon radiation therapy.[50] A subsequent, randomized study from the same group compared fast-neutron radiation therapy with standard photon radiation therapy. Local-regional control was improved with neutron treatment, but no difference in OS was seen, although follow-up was shorter in this trial. Fewer complications were seen with the use of a multileaf collimator.[51] Proton-beam radiation therapy is also under investigation.[52]
    6. Ultrasound-guided percutaneous cryosurgery is under clinical evaluation. Cryosurgery is a surgical technique under development that involves destruction of prostate cancer cells by intermittent freezing of the prostate with cryoprobes, followed by thawing.[53][Level of evidence: 3iiiC]; [54]; [55][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, and rectal injury. The technique of cryosurgery is under development. Impotence is common. 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.[54,55]
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