Prostate Cancer Treatment Protocols 

Updated: Feb 23, 2018
  • Author: Winston W Tan, MD, FACP; Chief Editor: E Jason Abel, MD  more...
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Treatment Protocols

Treatment protocols for prostate cancer are provided below, including general treatment recommendations and those for localized prostate cancer, for recurrent disease, and for advanced or metastatic disease.

See Prostate Cancer: Diagnosis and Staging, a Critical Images slideshow, to help determine the best diagnostic approach for this potentially deadly disease.

Also, see the Advanced Prostate Cancer: Signs of Metastatic Disease slideshow for help identifying the signs of metastatic disease.

General treatment recommendations for prostate cancer

Selecting initial treatment requires assessing the risk of the disease spreading or progressing, which is based on evaluating the patient's life expectancy, comorbidities, biopsy grade (Gleason score), clinical stage, and prostate-specific antigen (PSA) level.

Treatment recommendations for clinically localized prostate cancer

Very low risk of recurrence:

  • Patients with clinical stage T1c, Gleason score ≤6, PSA </li>

  • Active surveillance includes periodic PSA testing, digital rectal examination (DRE), and prostate biopsy. The optimal protocol for surveillance is still unknown, [1, 2, 3] but may include PSA as often as every 3 mo or at least every 6 mo, DRE as often as every 6 mo but at least every 12 mo, and repeat biopsy within 18 mo but as often as every 12 mo or if PSA and DRE change [4, 5, 6]

  • For treatment recommendations for patients with a life expectancy ≥20 y, see initial therapy for Low Risk of Recurrence, below

  • </ul>

    Low risk of recurrence:

    • Treatment for patients with clinical stage T1-T2a, Gleason score 2-6, PSA 7</ref>

    • Treatment for patients with a life expectancy ≥10y includes active surveillance or

    • Radical prostatectomy (RP) with or without pelvic lymph node dissection (PLND); RP is the standard therapy for localized prostate cancer, involving the removal of the prostate and seminal vesicles with or without pelvic lymph nodes; this may be done using either open or laparoscopic (robotic-assisted) technique [3, 8, 9] or

    • External beam radiation therapy is a standard therapy for patients with localized disease; 3-dimensional (3D) techniques such as 3D conformal radiation treatment (3D-CRT) offer reduced toxicity and the use of higher doses; second-generation techniques, including intensity-modulated radiation therapy (IMRT), are also required, especially if doses ≥78 Gy are administered [10]

    • Radiation therapy doses of 75.6-79 Gy in conventional 36-41 Gy fractions to the prostate [10] with 3D-CRT/IMRT with daily image-guided radiotherapy (IGRT) or brachytherapy (recommended dose rate: 145 Gy for iodine-125 and 125 Gy for palladium-103): A study by Haverkort et al found that position verification using gold markers and reduced planning target volume margins yielded adequate treatment of the prostate and a lower rectal wall dose in patients treated with curative external beam radiotherapy [11]
    • Patients with low-risk cancer are not candidates for pelvic lymph node irradiation or ADT [12]

    Intermediate risk of recurrence:

    • Treatment options for patients with clinical stage T2b-T2c, Gleason score 7 or PSA 10-20 ng/mL, who have a life expectancy or</b>

    • Radiation therapy (doses of 78-80+ Gy) with 3D-CRT/IMRT with daily IGRT with or without short-term neoadjuvant/concomitant/adjuvant ADT for 4-6 mo with or without brachytherapy (recommended dose rate: 145 Gy for iodine-125 and 125 Gy for palladium-103) [13, 14]

    • Treatment recommendations for patients with a life expectancy ≥10 y include RP with PLND or

    • Radiation therapy (doses of 78-80+ Gy) with 3D-CRT/IMRT with daily IGRT with or without short-term neoadjuvant/concomitant/adjuvant ADT for 4-6 mo with or without brachytherapy (recommended dose rate: 145 Gy for iodine-125 and 125 Gy for palladium-103)

    • Intermediate-risk cancers consider combining brachytherapy (recommended dose rate: 145 Gy for iodine-125 and 125 Gy for palladium-103) with external beam radiation therapy (EBRT)(40-50 Gy) with or without 4-6 mo neoadjuvant/concomitant/adjuvant ADT

    • Administering ADT before, during, and after radiation prolongs survival [15]

    High risk of recurrence:

    • Clinical stage T3a, Gleason score 8-10, PSA >20 ng/mL

    • Treatment options include RP plus PLND for selected patients or

    • Radiation therapy (doses of 78-80+ Gy) with 3D-CRT/IMRT plus long-term neoadjuvant/concomitant/adjuvant ADT for 2-3 y or

    • Radiation therapy (doses of 78-80+ Gy) with 3D-CRT/IMRT with daily IGRT plus brachytherapy (recommended dose rate: 145 Gy for iodine-125 and 125 Gy for palladium-103) with or without short-term neoadjuvant/concomitant/adjuvant ADT for 4-6 mo or

    • High-risk cancers may be treated with combination EBRT (40-50 Gy) and brachytherapy with or without 4-6 mo neoadjuvant/concomitant/adjuvant ADT

    Alternative treatment recommendations for localized prostate cancer

    Other treatments that have been used in the initial management of localized prostate cancer include the following:

    • Cryotherapy
    • High-intensity focused ultrasound
    • Particle beam therapy

    Cryotherapy:

    • Cryotherapy (also known as cryosurgery or cryoablation) involves using transrectal ultrasonographic guidance; percutaneous cryoprobes are placed and used to freeze prostate tissue

    • This treatment is not preferred as a standard curative treatment option but may be used in select patients with localized prostate cancer or as focal therapy in low-risk patients (experimental) [16]

    • Can also be considered as salvage therapy after failed radiation therapy [17]

    • Complications include tissue sloughing, perineal ecchymosis, stricture or contracture, incontinence, impotence, and fistula formation between the urinary and gastrointestinal tracts

    High-intensity focused ultrasound [18] :

    • Acoustic ablative technique that uses ultrasound to induces immediate and irreversible coagulative necrosis with sharply delineated boundaries; performed under spinal anesthesia on an outpatient basis
    • Widely used outside the United States; approved for ablation of prostate tissue by the US Food and Drug Administration in 2015 [19]
    • Used for both whole-gland treatment and focal therapy (“male lumpectomy”) [20]

    Particle beam therapy [21] :

    • Radiation therapy that uses protons for energy; outside the United States, carbon ions are also used
    • Performed at specialized facilities
    • Combined use of proton beam therapy with standard radiotherapy resulted in a relatively higher occurrence of severe gastrointestinal and genitourinary toxicities
    • Proton beam therapy alone has produced favorable outcomes with respect to disease control and toxicity
    Biochemical failure

    See the list below:

    • Approximately 20-30% of patients treated with intent for cure will have biochemical recurrence, which most commonly manifests as a rising PSA level [22, 23]

    • Biopsy of the prostatic bed is usually not recommended unless the patient is a candidate for salvage therapy

    • Monitor PSA, alkaline phosphatase, and calcium every 6 months to determine whether the doubling time is less than 1 year

    Post–radical prostatectomy recurrence

    See the list below:

    • Defined as a detectable PSA that increases on two subsequent measurements or a PSA that fails to fall to undetectable levels

    • Best PSA threshold unknown but probably between 0.2 and 0.4 ng/mL [24]
    • PSA that fails to fall to undetectable levels after prostatectomy may indicate residual prostate cancer or prostate cancer

    • Treatment options include salvage radiation therapy, androgen deprivation, and surveillance

    • Adjuvant radiation therapy may be more beneficial than salvage radiation therapy in men with poor pathologic features [2, 3]

    Post–radiation therapy recurrence

    See the list below:

    • Defined as a rise in PSA of 2 ng/ml or more above the nadir [25, 26, 27]

    • PSA can bounce up and down after radiation

    • Treatment options include salvage prostatectomy, ADT, surveillance, high-intensity focused ultrasound (clinical trials), cryotherapy, repeat irradiation

    Treatment recommendations for locally advanced prostate cancer

    Very high risk:

    • Clinical stage T3b-T4 treatment options include radiation therapy (doses of 78-80+ Gy) with 3D-CRT/IMRT plus  long-term neoadjuvant/concomitant/adjuvant androgen deprivation therapy (ADT) for 2-3 y or

    • Radiation therapy (doses of 78-80+ Gy) with 3D-CRT/IMRT with daily IGRT plus brachytherapy with or without short-term neoadjuvant/concomitant/ADT for 4-6 mo or

    • RP plus PLND for selected patients (those with clinically localized prostate cancer that can be completely excised surgically, life expectancy of at least 10 years, and no serious comorbid conditions that would contraindicate elective surgery) [7]   or

    • ADT alone, in patients with T3 disease and/or node-positive disease and PSA doubling time less than 10 months

    • Nonmetastatic castration-resistant prostate cancer can be treated with apalutamide 240 mg (ie, four 60-mg tablets) PO daily; administer with GnRH analog concurrently, unless the patient has had bilateral orchiectomy [28]

    Metastatic disease:

    • Any T, N1: Treatment includes ADT or radiation therapy (doses of 78-80+ Gy) with 3D-CRT/IMRT with IGRT plus long-term neoadjuvant/concomitant/adjuvant ADT for 2-3y

    • Any T, any N, M1: Treatment includes only ADT for patients with M1

    Androgen deprivation therapy (ADT) recommendations for advanced or metastatic disease

    See the list below:

    • ADT is a preferred initial treatment for symptomatic metastatic prostate cancer because androgenic effects promote the growth and malignant transformation of prostatic tissue [29]

    • ADTs include luteinizing hormone (LH) receptor agonists (eg, histrelin, leuprolide), gonadotropin-releasing hormone (GnRH) receptor agonists (eg, goserelin, histrelin, leuprolide, triptorelin) and antagonists (eg, degarelix), and complete androgen blockade (CAB)

    • CAB includes medical castration with an oral antiandrogen (eg, bicalutamide, flutamide, nilutamide) or surgical castration [30]

    • Patients who do not show an adequate suppression of serum testosterone (</li>

    • Monotherapy with nonsteroidal antiandrogens is less effective but these agents are associated with fewer hot flashes and fatigue and do not impair libido

    • If hormone therapy fails, that therapy should be continued into and through the next hormone manipulation

    • </ul>

      Gonadotropin-releasing hormone agonists:

      • Therapy with GnRH analogs may induce medical castration by suppressing luteinizing hormone (LH) production

      • These agonists can potentially cause a transient surge of LH when therapy is initiated before the LH levels fall (flare phenomenon)

      • GnRH agonists are offered in 1 mo, 3 mo, and once-yearly depots; premedication with antiandrogen is necessary to prevent flare phenomenon

      • Leuprolide: 7.5 mg intramuscularly (IM) monthly or  22.5 mg IM every 3 mo or  30 mg IM every 4 mo or  45 mg intravenously (IV) every 6 mo or

      • Histrelin: one 50-mg subcutaneous (SC) implant every 12 mo [31] ; continue therapy until disease progression or

      • Goserelin: 3.6-mg implant SC monthly or  a 10.8-mg implant [31] SC every 3 mo or

      • Triptorelin: 3.75 mg IM monthly or  11.25 mg IM every 3 mo or 22.5 mg IM every 6 mo

      Gonadotropin-releasing hormone antagonists:

      • Pure GnRH antagonists suppress testosterone and avoid the flare phenomenon associated with GnRH agonists
      • Important for patients with no prior hormone treatment who are diagnosed with significant metastasis.
      • Degarelix: 120 mg SC x two doses (ie, two separate injections totaling 240 mg), then, after 28 days, monthly maintenance doses of 80 mg SC

      Nonsteroidal antiandrogens for non–castrate-resistant disease:

      • Antiandrogens bind to androgen receptors and competitively inhibit their interaction with testosterone and dihydrotestosterone

      • These agents do not decrease LH levels and androgen production

      • Antiandrogens are usually used in combination with a GnRH agonist, to prevent a disease flare caused by the transient increase in testosterone levels

      • Flutamide 250 mg orally (PO) TID or

      • Bicalutamide 50 mg PO daily; patients refractory to other antiandrogen agents may start with 150 mg PO daily or

      • Nilutamide 300 mg PO daily for 30 days, and then  150 mg PO daily or

      • Enzalutamide (160 mg PO daily), which was previously indicated only for metastatic castration-resistant prostate cancer in patients who had received docetaxel; it is now approved also for patients who have not received chemotherapy [32]

      Chemohormonal therapy for hormone-sensitive metastatic disease

      • Docetaxel 75 mg/m 2 IV, with dexamethasone premedication 8 mg PO at 12 hours, 3 hours, and 1 hour before docetaxel infusion; repeat cycle every 21 days for up to a total of six cycles [33]
      • Abiraterone Acetate 250mg/tablet , 4 tablet po daily, prednisone 5 mg po bid daily
      • Enzalutamide  40 mg/tablet, 4 tablet po daily

      Castrate-resistant metastatic disease

      • Docetaxel 75 mg/m 2 IV, with dexamethasone premedication 8 mg PO at 12 hours, 3 hours, and 1 hour before docetaxel infusion; repeat cycle every 21 days for up to a total of 10 cycles

      • Abiraterone acetate 250 mg/tablet, 4 tablets PO daily plus prednisone 5 mg PO BID
      • Enzalutamide  40 mg/tablet, 4 tablets PO daily
      • Radium-223 50 kBq (1.36 microcurie) per kg IV infused over 1 minute; repeat q 4 wk for six cycles total; dosage calculation must be based on decay correction factor of radium-223
      • Sipuleucel-T requires three complete doses IV given at approximately 2 wk intervals (median dosing interval, 2 wk; range, 1-15 wk); infuse IV over 60 min; premedicate with oral acetaminophen and an antihistamine approximately 30 min prior to administration [34, 35, 36, 37]  Men with less advanced disease, good performance status, life expectancy >6 mo, no visceral disease, and no or minimal symptoms and who are resistant to standard hormone treatment may be candidates for autologous immunotherapy with sipuleucel-T [34]
      Treatment recommendations for castration-resistant prostate cancer

      See the list below:

      • All patients with metastatic disease become resistant to ADT

      • Radiation may be used for palliation in patients with painful bone metastases or impending spinal cord compression

      • Surgical intervention may be necessary for weight-bearing bones involved in pathologic fracture

      • Therapeutic options are limited, and the focus is on improving quality of life using single or multimodal therapies

      • Docetaxel every 3 wk plus prednisone is the treatment of choice for men with symptomatic castration-recurrent prostate cancer; [38, 39, 40] recommended dose is docetaxel 75 mg/m2 IV on day 1 plus prednisone 5 mg PO BID; repeat cycle every 21 days for up to a total of 10 cycles (premedicate with oral corticosteroids starting 1 day before docetaxel administration to reduce incidence of hypersensitivity reactions and fluid retention)

      • Abiraterone has been approved for the treatment of patients with metastatic castration-resistant prostate cancer who are either chemotherapy-naive or who have had prior docetaxel therapy; recommended dose is 1000 mg PO once daily plus  prednisone 5 mg PO BID [36, 37, 41, 42] ; in addition, de Bono et al reported that abiraterone prolonged overall survival in patients with metastatic castration-resistant prostate cancer who had received prior chemotherapy. [43]

      • Cabazitaxel with prednisone can be used for patients who have hormone-refractory metastatic prostate cancer that was previously treated with a docetaxel-containing treatment regimen; cabazitaxel 25 mg/m2 IV every 3 wk; infuse IV over 1 h; use inline filter (0.22 µm) during administration plus  prednisone 10 mg PO daily; reduce cabazitaxel dose to 20 mg/m2 with prolonged or febrile neutropenia or with persistent or severe diarrhea

      • Enzalutamide 40 mg/tablet, 4 tablets PO daily
      • Symptomatic men who are not candidates for docetaxel-based regimens may be candidates for mitoxantrone 12 mg/m 2 IV on day 1 plus  prednisone 5 mg PO BID daily; repeat cycle every 21 days [38, 39, 40]

      Treatment recommendations for patients with castration-recurrent prostate cancer and bone metastases

      Bisphosphonates are recommended for all men with hormone-refractory prostate cancer and bone metastases [44, 7] Bisphosphonates have been shown to reduce skeleton-related events such as pathologic fracture. Optionss are as follows:

      The radiopharmaceutical radium-223 dichloride (Xofigo) is approved for men with castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastatic disease:

      • 50 kBq (1.36 microcurie) per kg IV infused over 1 minute; repeat q 4 wk for six cycles total; dosage calculation must be based on decay correction factor of radium-223 (listed in prescribing information) [45]