Management of high-risk prostate cancer – a summary of findings

This review evaluated recent evidence on the management of high-risk prostate cancer. Primary treatment options for high-risk prostate cancer were generally associated with good effectiveness, but authors advised that risk assessment is in need of refinement and standardization.

About 15% of men with prostate cancer are diagnosed with high-risk disease. Men with high-risk prostate cancer (HRPC) are at increased risk of disease recurrence after treatment. Most definitions of HRPC include an advanced tumor stage (2c or higher), aggressive cancer cells (Gleason score of 8 or higher), or PSA (prostate specific antigen; a protein elevated in the blood in prostate cancer) levels higher than 20 ng/ml. Advances in treatments and early detection have significantly improved survival. However, prognoses and treatment outcomes for HRPC patients vary greatly. This review examined the current literature on the management of high-risk disease.

Multiple trials have reported improved overall survival (proportion who have not died from any cause since treatment) and disease recurrence rates for high-risk patients when radiation therapy was added to androgen deprivation therapy (ADT; standard hormone therapy). One noted that 7-year overall survival rates were 66% for ADT alone compared to 74% for ADT plus radiation. 7-year cancer-specific survival rates (proportion who have not died from prostate cancer since treatment) were 79% for ADT alone and 90% for ADT plus radiation.

Long-term ADT can increase the risk of side effects. One trials involving 22,961 men noted increased hot flushes, insomnia and decreased sexual interest with long-term ADT. But short-term ADT has been associated with decreased survival rates. The 10-year outcome of one trial involving 1,554 men showed higher cancer-specific survival when ADT was 28 months (88.7%) compared to 4 months of ADT (83.9%). Disease recurrence rates were also lower for long-term ADT (12.3%) compared to short-term (22.2%).

Gradually increasing (escalating) the doses of radiation was associated with better cancer control in five separate randomized trials. Men receiving the higher doses of external beam radiation (EBRT) had improved recurrence-free survival at 9 years (79%) compared to lower doses (57%). At 10-year follow-up, death from prostate cancer was 4% for the higher dose radiation group and 16% for the lower dose radiation group. Higher doses of radiation were also associated with a reduced rate of distant metastases. The addition of brachytherapy (form of radiation where radiation source is placed in the prostate) to EBRT and ADT can also improve outcomes. One study demonstrated 10-year recurrence-free survival rates of 92.6% when all 3 therapies were combined.

Prostate surgery (involving the removal of the whole prostate gland and local lymph nodes) is another primary treatment option for HRPC. Eight separate trials reported 5-year recurrence-free survival rates between 55 and 71%. Cancer-specific survival rates ranged from 65% to 92% depending on the risk level of the cancer.  Another trial showed that prostate surgery reduced cancer-specific mortality at 15 years (14.6%) compared to watchful waiting (20.7%; no treatment received). The incidence of bone metastases was also lower for surgery (21.7%) than watchful waiting (33.4%). Extended pelvic lymph node removal is recommended for HRPC patients undergoing surgery.

Radiation therapy following surgery improved overall survival by 28% and metastasis-free survival by 29% at 10 years in one study. Another trial observed significantly longer time to disease recurrence with additional radiation (average 10.3 years) compared to surgery alone (average 3.1 years). Increased short-term side effects were reported with radiation therapy. These included rectal complications, total urinary incontinence, and a temporary narrowing of urine tract. However, another study saw no differences in side effects related to urinary or bowel function after 2 years. Quality of life at 5 years was also improved with additional radiation therapy. Some treatment centers opt for radiation therapy after surgery only if disease progression is noted (salvage radiation therapy).

Authors reported good effectiveness for primary treatment options for HRPC. However, authors advised that risk assessment is in need of refinement and standardization.

Discuss with your doctor the treatment options available to you.