Do I have Radiation Failure?
Radiation Therapy is the most common treatment for prostate cancer in men across the world. While most primary cancers are treated successfully, recurrence occurs in 22 to 69% of patients after treatment (1,2,3). Recurrent disease is typically detected by rising PSA levels.
"Among patients who develop recurrence, approximately one third have metastatic disease." according to Brian F Capin, M.D., Assistant Professor, Department of Urology, The University of Texas Cancer Center.
About 20 to 30 % of patients with recurrence after radiation have localized disease (2,4) and therefore are eligible for local therapy. However at present less than 2% are getting any local therapy (2,5). Locally recurrent prostate cancer after radiation therapy can have an aggressive natural history with poor outcomes if not treated. Local recurrence if untreated leads to progression locally with bleeding and pelvic pain. It also leads to systemic recurrence, metastases and reduced cancer specific survival (6)
Unfortunately, most patients with local recurrence are not being treated in a timely manner. This is because until recently the treatments available for patients with local recurrence were associated with severe morbidity such as rectal injury, incontinence and impotence.
Over 98% of patients with local recurrence are getting no therapy or systemic hormonal therapy. Hormone therapy or Anti androgen therapy (medical castration) is associated with side effects including memory loss, dementia, hot flashes, gynecomastia, loss of libido, bone fractures, weight gain, sarcopenia, as well as vascular and cardiac complications. Increased rates of heart disease and diabetes also occur among men on hormone therapy for prostate cancer due to impaired metabolic health and insulin resistance.
The availability of HIFU in the US is causing a complete reevaluation in this field.
HIFU has the same benefits as salvage surgery, can be performed in most men including a majority who are not medically fit for surgery and has more than 10 fold lower incidence of rectal injury and less then 50% of the incontinence of surgery.
For many men with prostate cancer recurrence after radiation failure, HIFU may be the only option for cure.Because of older age, other illnesses and side effects these men may not be able to receive salvage surgery, salvage radiation or hormone therapy.
Currently there is still controversy in defining cure after radiation.It is clear however that men who have rising PSA after it has reached its lowest level (nadir PSA) need to discuss getting a biopsy. It has been found that post radiation biopsies that are positive 2 years after radiation are associated with progression of disease and should be treated. Men with nadir PSA over 0.5ng/ml do poorly after salvage HIFU. Data from Sloan Kettering Cancer Center shows patients with local recurrence have mean PSA of 1.1.
Dr Marc Garnick Oncologist at Harvard Medical School states
'Many oncologists use a working definition that biochemical recurrence has occurred if PSA levels are greater than 1–2 ng/ml 12 to 18 months following initial treatment. Ideally, post-treatment PSA levels should be less than 0.5 ng/ml, but this is rare; levels of 0.6–1.4 ng/ml may occur.'
PSA over 1.5 indicates likely metastatic disease. It is important to diagnose local recurrence early to not lose opportunity for window of cure.
Newer tests such as multi parametric MRI and F18 PET scans may be useful to determine whether cancer is localized or if there is systemic disease.
Multiparametric MRI has been evolving as a useful imaging test to diagnose prostate cancer. Until recently diagnosis of prostate cancer was made by blind biopsies that sampled the entire gland in a systematic manner. Multi parametric MRI uses several parameters such as T2 weighted imaging (T2W), cell density (ADC map, DWI) and increased blood flow (DCE) to localize cancerous areas in the prostate. This allows better mapping of extent of recurrence and location to target biopsy and treatment. Newer PET scans are able to localize small areas of metastatic cancer anywhere in the body and further helps to accurately stratify risk/benefits of local and systemic treatments.
With availability of HIFU more men have a better chance of long term survival with good quality of life. HIFU can be performed in men who are not able to have surgery because of age, poor health and other illnesses.
Men who have recurrence after radiation have significant scar tissue and fibrosis due to radiation.The anatomy is distorted and urethra is rigid secondary to fibrosis and decreased blood flow. Repeat salvage radiation will reduce blood supply further.This will increase risk for rectal fistula, incontinence and radiation induced hemorrhagic cystitis. Radical surgery has a limited role in these men since it requires tremendous expertise and is still associated with high incidence of rectal injury, incontinence and erectile dysfunction. At present less than 2% of men with local recurrence are getting salvage surgery due to side effects and risk.
HIFU can be performed as an outpatient therapy with low morbidity and men are more able to tolerate the procedure in spite of older age, and other medical illness.The procedure does not involve needles, scalpel or radiation.
Limited studies have reported that treatment of the prostate with radiation or radical surgery is beneficial in prolonging survival even in men who present with metastatic prostate cancer. It is hard to justify surgery and its morbidity in men with metastatic prostate cancer.
The concept of treating the prostate in men with limited metastases, can be tested more extensively with HIFU since the procedure does not cause major morbidity and can be performed as an out patient procedure.
2) Agarwal P et al Cancer. 2008 Jan 15;112(2):307-14
3) Kuban D et al Int J Radiat Oncol Biol Phys. 2003 Nov 15;57(4):915-28.
4)Bolla M Lancet Oncol. 2010;11:1066–1073.
5)Grossfeld G Urol.2002;168,530
6) Hematology/Oncology Clinics of North America, Volume 27, Issue 6, Pages 1205-1219