EAU PCa 2018: What Urologists Need to Know About Radiotherapy
The PROTECT study, randomizing patients with localized prostate cancer to surgery, radiotherapy or active monitoring demonstrated no difference in the oncological outcomes between the surgery and radiotherapy arms.1 When comparing patient-reported outcomes from the PROTECT study between patients treated with surgery and those treated with radiotherapy, the urinary function was seen to be slightly worse in the surgery group although this difference disappeared later. However, bowel function was seen to be worse in the radiotherapy group.
Dose escalation in radiotherapy produces better outcomes regarding biochemical control and disease recurrence, but no difference in overall survival was witnessed. Hypofractionation, which is the use of fewer fractions with a larger dose per fraction, is as effective and safe as conventional fractionation, and moderate hypofractionation (<3.4 Gy per fraction). Generally, hormonal therapy is not given with external beam radiotherapy (EBRT) for low-risk disease and only given for a short duration for intermediate risk disease, without any significant side effects, according to the speakers.
The European Association of Urology (EAU) guidelines state that in low-risk disease low dose brachytherapy or intensity modulated radiation therapy (IMRT) should be offered to patients without hormonal therapy. For intermediate risk disease, either low dose brachytherapy or EBRT in combination with short-term hormonal therapy (4-6 months) can be offered to patients.
Next, the topic of secondary malignancies resulting from radiotherapy was discussed. In a meta-analysis published in European Urology2 comparing radiotherapy to surgery, a clear advantage for surgery was demonstrated in all aspects. Furthermore, a much higher risk for developing bladder, colon and rectal cancer was seen in the radiotherapy-treated patients. However, when looking closely at the data, this translates only an extra 1-2 cases per hundred patients. Furthermore, this analysis is limited due to the inability to exclude confounding factors such as obesity and smoking, which are known cancer risk factors. Lastly, the control group, composed of patients who underwent radical prostatectomy, are a highly selected group of patients, which have a much lower risk for developing secondary cancers, when compared to the general population, and therefore is not the appropriate control group.
The posttreatment PSA nadir is highly predictive of distant failure and cancer-specific death. This has been shown to be more predictive than the pre-treatment PSA.3 When PSA nadir is less than one ng/ml, the cancer-specific survival (CSS) is 98%, when it is 1.1-2 ng/ml the CSS is 96%, and when it is above two ng/ml, the CSS drops significantly to 76%. It is also important to remember that reaching the PSA nadir can take a long period ranging from 2-114 months (with a median of 32 months).3
In the past, the definition of biochemical recurrence after radiotherapy was made according to the ASTRO criteria (1997), which is three consecutive increases in postradiotherapy PSA levels after the nadir. The date of failure is backdated to the time midway between the PSA nadir and the first of the three increases. However, in 2006 the Phoenix criteria were established, stating that a rise by two ng/ml or more above the nadir PSA (defined as the lowest PSA achieved) should be considered as the current standard definition for biochemical failure after radiotherapy. This stays consistent with or without short-term hormonal therapy.
Lastly, Dr. Mason and Dr. Bossi discussed the evaluation of patients for salvage radiotherapy. There are three questions that need to be answered before embarking on salvage radiotherapy for any patient. First, is cancer potentially curable? (T1-T3a N0M0 disease, PSA <10 ng/ml, without any evidence of metastases, and a positive re-biopsy). Second, is the patient appropriate for this therapy? The patient should be in good health, with a life expectancy of more than ten years. The patient needs to be highly motivated, and willing to accept the risks associated with salvage therapy. Third, the treatment must be safe for its entire duration.
Presented by: Malcolm D. Mason, Cardiff, Great Britain, and Alberto Bossi, Villejuif, France
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Twitter:@GoldbergHanan at the 2nd EAU Update on Prostate Cancer (PCa18)– September 14-15, 2018 – Milan, Italy
References:
1. Hamdy et al. NEJM 2016
2. Wallis et al. Eur Urol 2016
3. Hanlon AL et al. IJROBP 2002