Is radiotherapy the work of the devil?

In this issue, Ma et al. 1 have published a provocative article assessing the burden of radiotherapy (RT) complications on a busy tertiary urology service. Over a 6-month period, 21 patients contributed to 33 admissions attributed as RT complications, accounting for 1.4% (13/924) of elective admissions and 7.2% (20/277) of emergency admissions. The majority were for control of bleeding but there were four sobering cases of major morbidity necessitating either a urinary diversion or cystoprostatectomy. Genitourinary cancers account for ~20% of new cancer diagnoses in Australia [https://prostate-cancer.canceraustralia.gov.au/statistics] and whilst optimal RT usage is estimated to be in the order of 50–60% 2, actual use is significantly lower, often due to an emphasis on complications reflected by articles such as this. It is well recognised that patients who are older and have greater baseline comorbidities often receive RT rather than surgery 3, which is reflected in this series. Here, the median age was 79 years with no patients aged <71 years, more than half were on anti-coagulation, a third were diabetic or had prior long-term steroid use, and 80% had an American Society of Anesthesiologists (ASA) score of ≥3 indicating severe systemic disease. Any patients with such co-morbidity would be at risk of major complications following any treatment modality. However, trying to deny such patients potentially curative treatment exposes them to even greater morbidity from the debilitating symptoms of uncontrolled local disease progression. Therefore, offering high-dose RT, in the knowledge that some may experience complications such as those seen in this report, is often better than the alternatives. As the purpose of this study 1 was to report on admissions due to RT toxicity, there has been no focus on admissions that were due to side-effects of definitive surgery. Even if there were, as 26% of RT admissions were in patients that had undergone a prior radical prostatectomy (RP), so are complications such as strictures or lymphocoeles due to the surgery or radiation? This raises the issue of ascertainment bias, as there is no information on how the 'cause' of toxicity admissions was determined by authors. A critical missing piece of information is the lack of data on patient numbers having received RT for pelvic cancers in the previous 9 years at centres related to this tertiary service. This means we cannot determine what percentage of RT patients in this unit experience side-effects necessitating admission. Are the severe events mentioned a one in a 1 000 phenomenon or one in 100? We do not know from these data. The big question that is touched upon but not addressed by this study 1 is that, if faced by a patient where all treatment options are appropriate, are there differences in complications and quality of life following RT or surgery? The only valid comparison we have with 10-year follow-up is the Prostate Testing for Cancer and Treatment (ProtecT) trial. This prospective study randomised 1 643 men with localised prostate cancer to active monitoring, RP or external beam RT (EBRT). There was no difference in prostate cancer-specific mortality or disease progression between RP and EBRT at 10 years 4. Patient-reported outcomes at 6-years follow up 5 indicated that global quality-of-life was virtually identical between surgery and RT. Surgery had the greatest negative effect on urinary continence and sexual function over 6 years. However, bowel function, urinary voiding and nocturia were worse in the RT group, although considerable recovery for symptoms was seen after 6 months. There have been numerous improvements in RT technique over the past 10 years. This article 1 is a timely reminder to radiation oncologists about the importance of optimal RT technique to reduce the risk of complications. Almost two-thirds of patients in this study received standard EBRT with <20% receiving intensity-modulated RT (IMRT) techniques, which have been shown to reduce dose to critical adjacent structures 6, reduce rates toxicity, and is the standard of genitourinary care in many radiation oncology departments. The use of image guidance to ensure accuracy of treatment is critical. At the Memorial Sloan-Kettering Cancer Center 7 image guidance in addition to IMRT more than halved the risk of late grade 2+ GU toxicity. Inserting hydrogel, a rectal spacer, to move the rectum out of harm's way during prostate RT has also been shown to reduce late rectal complications 8. More accurate imaging with MRI and prostate-specific membrane antigen positron emission tomography (PSMA PET) allow better tailoring of doses to the gross disease and reduce dose to sensitive areas such as the bladder neck, a region where many complications occur. This study highlights 1 the importance of the various disciplines involved in the management of genitourinary cancers working closely together to ensure the best possible outcomes for patients. As demonstrated in this paper 1, there are many circumstances where radiation oncologists rely on the support of their urological colleagues to manage these hopefully rare side-effects of RT. Similarly, RT plays an important role in the 25–30% of surgical patients who will experience a biochemical relapse following surgery. Working closely together we can provide balanced information to patients, give guidance when one treatment modality may be preferred over the other, and to support each other when things do not go as planned. None.