Non-Surgical Treatment

 

What non-surgical treatment options exist for prostate cancer?

In addition to surgery, the following options exist for treating prostate cancer. Each treatment has its own profile of complications including cancer recurrence, erectile dysfunction, incontinence and medical complications surrounding the procedure.

  • External beam radiation therapy (EBRT)
  • Brachytherapy
  • High intensity focused ultrasound (HIFU)
  • Watchful waiting
  • Active surveillance
  • Hormone therapy
 

What are active surveillance and watchful waiting?

Patients undergoing watchful waiting are those who also choose not to pursue initial treatment but intend to wait until their cancer is advanced before pursuing palliative therapy. This is generally only a recommended option for those patients who are likely to pass away in the next few years from some disease other than prostate cancer.

Patients under active surveillance [5] are those with known low risk prostate cancer who choose to watch their cancer and follow-up frequently with the intention of seeking curative therapy should it progress. Initially, patients have a biopsy performed as well as a PSA test and digital rectal examination to determine the aggressiveness of their cancer. Patients whose cancer does not appear to be aggressive based on these investigations meet the inclusion criteria for an active surveillance program. In theory, older patients with a localized low grade cancer and low PSA would benefit most from enrolling in an active surveillance program. The rationale behind this is that treatment for a cancer that is unlikely to incur morbidity or mortality will  cause a greater quality of life impact than the cancer itself.

Once enrolled in an active surveillance program, they are followed according to a surveillance protocol. This involves being followed at regular intervals with:

  • PSA levels (about every 3 months)
  • Biopsy (at 1 year and then every few years)
  • Digital rectal examinations (at each visit)

Additionally, patients may or may not be prescribed dutasteride while on active surveillance. A recent study (REDEEM study) suggested that this decreased cancer progression–however significant criticism of this trial exists, including the fact that the trial was not blinded and that receiving treatment for cancer was considered as cancer progression. It is unclear whether or not this drug offers a benefit. 

 
Active surveillance bears the real risk that the cancer that is not being treated may metastasize and cause morbidity and mortality. Preventing these detrimental effects relies on the accuracy of initial investigations of the cancer’s aggressiveness and how good our surveillance protocols are. Details on the best surveillance protocol and inclusion criteria are still being ironed out.

Patients undergoing active surveillance may have difficulty with the program for psychological reasons. Repeated biopsy of the prostate may result in complications of the biopsy including pain, bleeding into the stool, urine and ejaculate, severe infection and urinary issues. There is also likely a slightly increased risk of erectile dysfunction with regularly repeated biopsy [5].

 

What is external beam radiation therapy?

External beam radiation therapy (EBRT) involves the use of externally applied beams of energy to precisely target the prostate and irradiate it. Think of this like a leaf burning when a magnifying glass focuses sunlight on it. Modern radiation therapy is a bit more elaborate than this metaphor because:

  • Using many “magnifying glasses” directed at the same target allows the energy delivered by each beam to be smaller, decreasing the radiation to tissues as the beam passes through them.
  • Imaging of the prostate allows us to know where exactly the prostate is, thereby allowing us to target the leaf and not a branch or another leaf on the same tree.
  • Modern computers will aid in interpreting the imaging to direct delivery of the radiation beam at an appropriate strength to all affected prostate tissue.
  • A precise template of tissue to be radiated is calculated and applied in modern technologies like intensity modulated radiation therapy (IMRT). This means a greater total energy can be delivered to the prostate when targeting is precise, thereby improving outcomes.
  • Additional therapy to decrease testosterone can be given in intermediate or high risk cancers which will improve survival. This is akin to not providing water to the plant supporting our poor leaf before and after burning it.
 

What are the side effects of EBRT?

Radiation injures the small blood vessels of the irradiated area. This may cause a number of adverse effects including [1]:

  • One third of patients may have symptoms of proctitis or cystitis during treatment and in 5-10% these may be permanent. Proctitis refers to inflammation of the rectum. This usually causes diarrhea, an inability to have bowel movements despite the urge (tenesmus), rectal bleeding, painful defecation and narrowing or obstruction of the rectum. Cystitis refers to inflammation of the bladder. This causes symptoms of painful urination, urgent needs to urinate with associated incontinence and bloody urine.
  • About half of patients develop erectile dysfunction secondary to EBRT. This begins a year or more after EBRT unlike the ED associated with surgery which occurs immediately.

Depending on how risky the prostate cancer is, androgen deprivation therapy may also be employed. This has fairly severe side effects of its own including erectile dysfunction and loss of libido, osteoporosis and bone fractures, hot flashes, loss of muscle and gain of fat, diabetes, cardiovascular disease, fatigue, low red blood cell count, male breast tissue, decreased penile and testicular size, thinning of body hair as well as emotional and cognitive changes [2].

 

How effective is EBRT?

EBRT is considered an effective form of cancer control and has similar efficacy to surgery. Technicalities in how cancer recurrence is measured do not allow a direct comparison for cancer control to be made. Nonetheless, most experts generally consider EBRT a viable alternative to surgery[1].

 

What is brachytherapy?

Brachytherapy involves the implantation of many bits of radioactive material into the prostate. These are called seeds and are usually comprised of radioactive palladium or iodine and placed through the rectum. While brachytherapy also relies on radiation, it differs from EBRT in that seeds are actually implanted into the prostate to deliver this radiation. These seeds are permanently implanted and are not removed, but lose their radioactivity after a period of time. Similar to modern EBRT, modern brachytherapy uses various technologies to improve localization of the prostate for appropriate seed placement [1].

 

What brachytherapy options are available for more advanced disease?

Traditional brachytherapy involving only the implantation of palladium or iodine radioactive seeds is recommended only for low-risk prostate cancer. For more advanced cases, needles are placed into the prostate through the skin. Radioactive iridium sources are then transiently inserted into these needles for short periods of time and then removed. This delivers a higher dose of radiation more consistently throughout the prostate and is thus called high dose rate (HDR) brachytherapy. This may also be combined with EBRT. The use of these techniques in non-low risk disease is promising but not extremely well established in terms of cancer control or side effects [3].

 

What are the side effects of brachytherapy?

Side effects of brachytherapy are similar to radiotherapy and generally include [3]:

  • Urinary symptoms. Most patients with brachytherapy initially experience some irritative urinary symptoms including frequent needs to urinate, urgent needs to urinate and painful urination. A small minority of patients will not be able to urinate after brachytherapy and require temporary catheterization or a small procedure. Urinary symptoms gradually resolve over a year but may flare up in the future. Less than 15% of patients will report increased urinary symptoms after a year. Urethral stricture (narrowing of the urethra) may also affect 15% of patients in the long run.
  • Proctitis may occur but less severely than EBRT.
  • Erectile dysfunction will affect at least half of treated patients and occurs years after brachytherapy is undertaken and depends on several factors including pretreatment erectile function.

Because seeds are physically being placed into the prostate, there is also the potential for bleeding, infection, and improper seed placement.

 

When should brachytherapy not be employed?

Brachytherapy should be used with caution in patients with underlying urinary symptoms, unfit for anesthesia, and large prostates. In cases of more severe disease, brachytherapy should be used in conjunction with other treatments such as EBRT or forgone entirely for EBRT or surgery [3].

 

What is HIFU?

HIFU stands for high-intensity focused ultrasound. High energy ultrasound waves are transmitted from an external probe to heat the prostate. This destroys cancerous and non-cancerous prostate tissue. HIFU is a newer therapy and less data supports its use in prostate cancer than traditional therapies such as surgery, EBRT or brachytherapy. HIFU is best avoided in intermediate or high risk prostate cancer, where it has not been well studied.

HIFU is a day procedure performed under spinal or general anesthesia and can only be performed on relatively small prostates. To prevent post-procedure urinary retention, patients are usually discharged home with a catheter that is eventually removed.

In the long term, erectile dysfunction affects about half of patients. Other side effects which occur in 20% or less of patients include urethral stricture, urinary incontinence and bladder neck contracture. The most severe complication includes rectourethral fistula occuring in about 1% of patients after their first treatment. The rate of rectourethral fistula increases with increasing treatments.

Source: 1 & 4

 

 

References

1. Campbell’s Urology 9th Edition.

2. UpToDate. Smith MR & Crawford ED. Managing the side effects of androgen deprivation therapy.

3. UpToDate. Roach M & DiBiase SJ. Brachytherapy for localized prostate cancer.

4. UpToDate. Klein EA. Overview of treatment for clinically localized prostate cancer.

5. UpToDate. Klotz L. Active surveillance for men with early prostate cancer.