Treatment Options

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An overview of treatment options

Treatment options can broadly be divided into those for patients with localized disease and those for patients with proven or presumed metastatic disease. Most men with localised disease will have the option of more than one treatment modality, and can select the treatment they feel is most suitable for them. For some men, the options will be more restricted because of the parameters of their disease or due to medical co-morbidities or physical characteristics. All patients should have an in depth discussion about the benefits and risks of each treatment so they can make an informed decision with their specialist about the best treatment option for them.

No one treatment fits all - each individual will have a treatment plan based on their own individual risk.

Localised Prostate Cancer

Active surveillance
Surgery
  • Open
  • Laparascopic (key-hole)
  • Robotic-assisted laparascopic
Radiotherapy (with or without hormone therapy)
  • Low Dose Rate Brachytherapy (seeds)
  • External Beam Radiotherapy (EBRT)
  • High Dose Rate Brachytherapy + EBRT
  • Combined Brachytherapy and EBRT
Other therapies
  • Whole gland High Intensity Focussed Ultrasound (HIFU)
  • Whole gland cryotherapy
Focal therapy (still experimental)
  • High Intensity Focussed Ultrasound (HIFU)
  • Cryotherapy

Advanced or metastatic prostate cancer

Hormone therapy
Chemotherapy
External beam radiotherapy (for the treatment of symptomatic bony metastases
Novel therapies
Radionuclides (e.g. Strontium)

 

The type of treatment available to each individual depends on the clinical stage and grade of the prostate cancer. The table below summarises the treatment options available across different clinical stages.

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Active Surveillance

The aim of active surveillance (AS) is to avoid treatment in men who do not require it.

Active surveillance involves close monitoring of the PSA, regular DRE examinations and interval prostate biopsies. Men with low risk, small volume disease are offered this modality, as evidence has shown that these cancers have a low risk of developing aggressive features and causing symptoms, or spreading outside the prostate. Active surveillance does not involve any active treatment of the prostate cancer. During follow-up, however, some men will proceed to treatment, either because of a change in the disease parameters, or through choice.

Active Surveillance is for men with low grade prostate cancer according to the following parameters:

  • PSA <10ng/ml

  • Gleason score 3+3=6

  • Normal DRE or small palpable abnormality

  • Small volume cancer on biopsy

These criteria are not strict and some surgeons will include men with disease parameters outside of those described above.

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Radical Prostatectomy

Radical prostatectomy involves the complete removal of the prostate and seminal vesicles. It is a suitable option for patients with localised and locally advanced prostate cancer and a life expectancy of at least 10 years. Some surgeons will also include removal of pelvic lymph nodes, particularly in patients with intermediate and high risk disease.

There are three main approaches to radical prostatectomy:

an open approach, which usually involves a lower abdominal incision 8-10cm in length, but is occasionally performed through an incision in the perineum (behind the scrotum). 

laparoscopic (keyhole surgery), whereby camera and working ports are placed through small incisions in the abdominal wall; or robotic, with a similar approach to laparoscopic, but with the addition of a device specifically developed to assist the surgeon with manipulation of the instruments.

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Radiotherapy

There are a number of different ways radiotherapy can be delivered. All radiotherapy is minimally invasive and involves the use of radiation to treat the cancer cells. The different types of radiotherapy available for prostate cancer are explained over the next few pages. 

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External Beam Radiotherapy

External beam radiotherapy is delivered to the prostate with an external source.  This technique is non- invasive, but radiotherapy is delivered with daily treatments over a 6-8 week period. The development of intensity modulated radiotherapy (IMRT) has allowed the delivery of higher doses to the prostate whilst sparing the surrounding tissues, in order to increase the treatment effect and minimise side effects. It is a suitable treatment option for patients with localised low and intermediate risk disease and a life expectancy of at least 10 years. It has also been used in high risk disease, although it is becoming more common for these patients to be offered multi-modal therapy, commencing with surgery and proceeding to radiotherapy if required. It is usually used in combination with hormone therapy in patients with intermediate or high risk disease. 

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Brachytherapy

Brachytherapy is the implantation of a radioactive isotope/s directly into the prostate, which delivers a high dose of radiation to the prostate whilst minimising the dose of radiotherapy delivered to surrounding tissues such as the bladder, rectum and urethra. The implantation of the isotope may be temporary or permanent.

Low Dose Rate Seed Brachytherapy is a permanent implant.  Multiple seeds are preloaded into needles and are implanted through the perineum into the prostate using ultrasound guidance. To determine the optimal placement of the seeds, the prostate is mapped to ensure the appropriate radiation dose is delivered to the target tissue whilst structures such as the urethra, bladder and rectum are relatively spared. Brachytherapy is suitable for low risk and some intermediate risk patients with organ confined disease (stage cT1b- T2b; Gleason score ≤ 7 on biopsy; initial PSA level of <15 ng/mL; smaller volume cancers) with a life expectancy of greater than 10 years. It is not suitable for patients with very large prostates as placement of the seeds can be difficult [1-3].

High Dose Rate Brachytherapy is a temporary implant. Typically about 18 plastic catheters (very thin tubes) are inserted through the perineum into the prostate using ultrasound guidance. The catheters remain in place and the patient then undergoes a planning procedure.  A single highly radioactive source that is welded on a wire is then positioned along the course of the catheters in multiple positions for various periods of time. Typically the time for treatment is 20 minutes and the source is then retracted. High dose rate brachytherapy typically is used in combination with a shorter course of external beam radiotherapy.

1.               Eylert, M.F. and R. Persad, Management of prostate cancer. Br J Hosp Med (Lond), 2012. 73(2): p. 95-9.

2.               Simmons, M.N., R.K. Berglund, and J.S. Jones, A practical guide to prostate cancer diagnosis and management. Cleve Clin J Med, 2011. 78(5): p. 321-31.

3.            Heidenreich, A., et al., Guidelines on Prostate Cancer. 2012, European Association of Urology.

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Other Therapies

Cryotherapy

Cryotherapy is a minimally invasive technique that uses freezing to kill prostate cancer cells (usually requiring around three days in hospital). Under the guidance of transrectal ultrasound, cryoprobes are placed into the prostate though the perineum. Pressurised argon and helium are delivered to the prostate through the probes. Argon freezes the prostate to temperatures around -40oC, while helium warms the cells; two repeat freeze-thaw cycles result in tissue damage and cell death [1].

High intensity focussed ultrasound (HIFU)

High intensity focussed ultrasound uses ultrasound waves at different intensities to destroy prostate cancer cells through the rectum. This minimally invasive technique uses two mechanisms of action to damage and kill cancer cells: high heat (>40oC >300oC) and the interaction of ultrasound and water micro-bubbles in the cell [1]. HIFU should be considered experimental, but may be offered to older patients with low to intermediate risk PCa (T1-T2b; Gleason score ≤7, PSA ≤20ng/ml) [2, 3, 4].

Focal Therapy

Focal therapies are still regarded as experimental treatments and more research is required before such treatments would be considered usual practice. The goal of focal therapy is to treat only the cancer within the prostate, whilst sparing the rest of the gland and in doing so, minimising the risk of side effects. Both Cryotherapy and HIFU can be used for focal therapy. Patients should not be offered focal therapy outside of clinical trials [5].

  1. Bozzini, G., et al., Focal therapy of prostate cancer: energies and procedures. Urol Oncol, 2012.
  2. Nomura, T. and H. Mimata, Focal therapy in the management of prostate cancer: an emerging approach for localized prostate cancer. Adv Urol, 2012. 2012: p. 391437.
  3. Cordeiro, E.R., et al., High-intensity focused ultrasound (HIFU) for definitive treatment of prostate cancer. BJU Int, 2012. 110(9): p. 1228-42.
  4. Palermo, G., et al., High-intensity focused ultrasound in prostate cancer: Today's outcomes and tomorrow's perspectives. Scand J Urol Nephrol, 2012.
  5. Eggener, S.E., et al., Focal therapy for localized prostate cancer: a critical appraisal of rationale and modalities. J Urol, 2007. 178(6): p. 2260-7.
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Hormone Therapy or Androgen Deprivation Therapy (ADT).

Prostate cancer is dependent on male androgens (such as testosterone) for growth. “Hormone therapy” refers to the restriction of these androgens in order to prevent the growth or cause shrinkage of prostate cancer; however it has not been shown to cure prostate cancer. Restricting androgens can be achieved by reducing the levels of circulating androgens, or blocking the androgens where they have their effect. Hormone therapy is most commonly delivered as a subcutaneous injection, but tablets can also be effective. In addition, a combination of injections and tablets can be effective when prostate cancer becomes resistant to a single mode of therapy.

A less common, but very effective method of androgen suppression, is the surgical removal of the testes (orchidectomy).

ADT may be used in combination with radiotherapy in organ confined (localised) disease for up to three years. It is thought that hormone therapy makes prostate cancer cells more sensitive to the radiotherapy dose [1,2]. 

  1. Pilepich MV, Winter K, Lawton CA et al., Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma--long-term results of phase III RTOG 85-31. Int J Radiat Oncol Biol Phys. 2005 Apr 1;61(5):1285-90.
  2. Bolla M, de Reijke TM, Van Tienhoven G, et al; EORTC Radiation Oncology Group and Genito-Urinary Tract Cancer Group. Duration of androgen suppression in the treatment of prostate cancer. N Engl J Med 2009 Jun;360(24):2516-27.
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Chemotherapy

Chemotherapy refers to treatment with chemical agents, which selectively kill cancer cells. Chemotherapy is only used in patients who have metastatic prostate cancer (where prostate cancer cells have spread beyond the prostate to distant sites such as bone or lymph nodes). Chemotherapy is reserved for patients who have already undergone treatment with androgen deprivation and in whom prostate cancer has become resistant to hormone therapy. Docetaxel is the most commonly used and most effective chemotherapy for advanced prostate cancer. 

  1. Heidenreich, A., et al., Guidelines on Prostate Cancer. 2012, European Association of Urology.
  2. Qi, W.X., Z. Shen, and Y. Yao, Docetaxel-based therapy with or without estramustine as first-line chemotherapy for castration-resistant prostate cancer: a meta-analysis of four randomized controlled trials. J Cancer Res Clin Oncol, 2011. 137(12): p. 1785-90.
  3. de Wit, R., Chemotherapy in hormone-refractory prostate cancer. BJU Int, 2008. 101 Suppl 2: p. 11-5.
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