PROSTATE CANCER AND SBRT

STORY / JAMES GRAHAM, PH.D.

Prostate cancer is the most common malignancy in men
and is a major cause of cancer deaths (one to two per
cent annually) in Australia and New Zealand.

More than 3000 men die in Australia every year from prostate cancer, making this cancer a greater risk of death than breast cancer in women.
The prostate is a small gland found just below the bladder and it surrounds the urethra, the tube that allows urine and semen to be passed. The
prostate gland function is to produce the seminal fluid that protects and nourishes sperm in semen.
As a man ages, the prostate is known to increase in size and this can cause problems such as difficulty in urinating. This prostate enlargement is often
benign and is not always a sign of prostate cancer.
The early stages of prostate cancer are often undetectable but as the disease progresses, discomfort when urinating, blood in the urine, and a painful lower back can be a sign of a developing prostate cancer.
Prostate cancer is more prevalent in developed countries and this is likely due to well-established risk factors such as age, race and family history as well as lifestyle and environmental risk factors.

When to get checked?

Men over the age of 50, or 40 if there is a family history of prostate cancer, should consider prostate cancer screening as part of their normal health check-up. Based on the doctor’s analysis of the patient’s prostate-specific antigen (PSA) levels, a decision on therapy can be made.
The PSA level in men over 50 years old is a validated and powerful predictor of a patient developing prostate cancer. However, balancing harm of treatment versus benefits is a delicate process that takes into account over-diagnosis rates, expected lifetime, and the present and future quality of life.

Treatment options

There is a wide array of treatment options available but a decision on which one to take is based on several risk assessments, including: a person’s age, stage of tumor, PSA count, Gleason score, and many other factors.
The Gleason score is derived from how a prostate biopsy analysis looks under the microscope and is a critical factor in how a doctor will assess risk. For example, if a prostate biopsy has a low Gleason score, then active surveillance would be the preferred choice rather than beginning potentially harmful treatment.
This risk assessment is based on several large studies that have suggested that for men who have a low-risk prostate cancer, there is just a one per cent risk of death, ten years after the initial prostate cancer diagnosis.
One of the most common forms of treatment is conventional external body radiotherapy (EBRT). EBRT involves a beam of radiation that is directed at the tumor and this is carried out during multiple sessions over an extended period of time.

Stereotaxic Body Radiotherapy

In recent years, stereotaxic body radiotherapy (SBRT) has emerged as an alternative option for the treatment of prostate cancer. SBRT was originally designed to treat brain tumors, because the radiation beam is so focused that it can precisely target the tumor.
A potential advantage of SBRT is that a larger dose can be provided and therefore will require a much shorter treatment time.
Treatment times for EBRT and other types of radiation are typically very long and can last several weeks, with daily trips to an oncology unit to receive radiation treatment.
At present, clinical trials on SBRT have just been confined to low-risk prostate cancer patients. However, this technology has shown a lot of promise with no relapses or complications for 94 per cent of patients after four years.
Further to this, a new phase I/II clinical trial was published in early 2016, which investigated the effect of SBRT on low and intermediate risk prostate cancers. The researchers carried out measurements after three and five years to determine treatment side effects, survival rates, as well as effect on quality of life.

Who and what was studied?

Phase I/II Clinical Trial
Phase I evaluated the tolerability of increasing doses of SBRT to treat low and intermediate-risk prostate cancer. Forty-five men enrolled in this study and they received either a low, intermediate or high dose of radiation across five treatment sessions. Researchers then followed these patients for up to 30 months to determine the benefits and side effects of the different doses of radiation.
In phase II, patients again received either a low, intermediate or high dose of radiation across five sessions but follow-up appointments were up to five years to measure the long term side effects as well as changes in quality of life and survival rates.

SBRT treatment results

Phase I Clinical Trial
The phase I clinical trial showed that for men with low and intermediate risk prostate cancers, there were minor side effects that were relatively manageable with no serious symptoms recorded.
More promisingly, the patient survival rates were 79 per cent, 85 per cent and 92 per cent for the low, intermediate and higher doses of SBRT, respectively. This is also evidenced by the fact that 44 out of the 45 men who took part, all had declining or stable PSA score measurements.

Phase II Clinical Trial

In the phase II clinical trial, side effects were again manageable but just for the low and intermediate dosage groups. However, in the high dose group there were some ongoing treatment complications.
After five years, cancer survival rates were 100 per cent for all three-treatment groups and encouragingly every patient was relapse free and had no signs of the cancer spreading.

What should we know from this clinical trial?
Overall, SBRT treatment results in excellent control of the cancer, even after five years. However, some men in the high dose group did have some serious side effects with treatment. Therefore, future clinical trials will need to carefully analyse and clarify how to balance dosage and long-term side effects.

Big picture

The phase I and phase II clinical trials showed that SBRT is an effective and safe treatment for low and intermediate-risk prostate cancer, when spread over five sessions.
These data are supported by previous trials that have shown that even very low radiation doses with SBRT can provide a 90 per cent success rate after three years post-treatment. In a second larger study, a similar low-dose SBRT treatment schedule resulted in 94 per cent of the men remaining relapse free after four years.
In this phase I/II study, the higher radiation dosage did cause some serious side effects and therefore this should be reserved for men who have a particularly aggressive form of prostate cancer, where the balance of benefits outweighs the chance of significant surgical interventions due to ongoing radiotherapy complications.
In comparison to other radiotherapy treatments such as more conventional therapies, relapse-free rates after five years can be as low as 69 per cent and 76 per cent. In addition, for surgical removal of the prostate, the chance of remaining relapse-free is still only between 65 per cent and 84 per cent for intermediate-risk prostate cancer.
Therefore, this study investigating SBRT shows that there is a significant improvement over the current options for long-term survival rates with relatively low risk of ongoing side effects.

Conclusion

For low to intermediate-risk prostate cancer, low and intermediate radiation doses across five sessions provides high PSA control with an acceptable level of side effects.