Muscle invasive bladder cancer, after diagnosis using TURBT, is usually treated with radical cystectomy with the option of neoadjuvant chemotherapy before surgery. However, another option is treatment with Radiotherapy with or without chemotherapy (radiosensitizer). These patients are then followed with cystoscopy, which can then lead to either salvage radical cystectomy for residual/recurrent invasive disease, or another TURBT with local treatment for the superficial disease recurrence.
Radiotherapy is an attractive option due to several reasons:
- It enables the preservation of bladder function
- It enables the preservation of sexual function
- It allows patients to maintain quality of life and their body image
- It avoids major surgery – which is especially important for elderly patients and/or patients with many comorbidities
Since the introduction of the therapeutic option of bladder preservation, Dr. Huddart has accumulated eight important lessons which he described next.
- Concomitant chemotherapy improves outcome. Several studies have demonstrated that chemotherapy confers improved overall survival to bladder cancer patients. There has been some work done to try to see if we can improve radiosensitization. Some potential targets include immunomodulation, EGFR, FGFR, DNA repair genes, HSP90, HDACi.
- Disease outcomes depend on the type of treatment and stage of cancer. The presence of residual mass, the extent of resection and tumor size are all related. The presence of residual mass was highly correlated with the extent of resection. Patients who are poor candidates for radiotherapy include those with:
- Large primary tumor with residual mass post TURBT especially in association with bilateral hydronephrosis
- Pure squamous or adenocarcinoma tumor
- Severe lower urinary tract symptoms
- Widespread CIS
- Contraindication to radiotherapy (inflammatory bowel disease, radiation sensitivity syndrome, previous pelvic radiotherapy)
- Patient unwilling to have a follow-up cystoscopy
- Radiotherapy can achieve survival like radical cystectomy. It is very difficult to compare between radiotherapy and radical cystectomy, as there are stage migration and selection biases.
- Toxicity of radiotherapy is generally modest, and average quality of life is maintained. Several studies have shown that the overall toxicity in radiotherapy is much lower than when compared to radical cystectomy. Comparison of quality of life parameters also demonstrates that at the beginning, immediately following treatment, there is a clear advantage favoring radiotherapy, but at long term follow-up, the quality of life is quite similar between both treatment modalities.
- Chemotherapy response selects a good prognosis group of patients but is probably not predictive.
- Hypofractionated radiotherapy is a good treatment for the elderly/frail patient. The phase 2 HYBRID trial1 randomized pT2-4a N0M0 bladder cancer patients unsuitable for standard daily radiotherapy to receive various weekly hypofractionated radiotherapy treatments. The median age of the patients in this trial is 85. The results demonstrated that the tumor was controlled in 77% of patients at three months. Median overall survival was 18 months. This trial proved that hypofractionated radiotherapy is a real option for those not fit enough for standard radical treatment.
- Standard radiotherapy is inaccurate and is improved by image guidance and adaptive techniques. Using adaptive radiotherapy strategies enables a more accurate radiotherapy treatment. These include increased target coverage, reduced margins, and reduced high-dose boost volume.
- Most recurrences are non-muscle invasive. Several studies have shown that most recurrences after radiotherapy are superficial and do not invade the muscle layer of the bladder (ranging from 40%-100%). Most patients are controlled after three months, with at least 50% of patients with postradiotherapy recurrences being superficial. It is not clear if it is possible to significantly reduce this number with systemic immunomodulation.
Figure 1 – Dr. Huddart's Vision for 2025:
Presented by: Robert A. Huddart, Reader and Honorary Consultant MA (Oxon), MB BS MRCP FRCR Ph.D., The Royal Marsden NHS Foundation Trust
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Twitter: @GoldbergHanan at the CUOS – Canadian Uro-Oncology Summit 2019, #CUOS19 January 10-12, 2019 Westin Harbour Castle, Toronto, Ontario, Canada
References:
1. Hafeez S. et al. Int J Radiat Oncol Biol Phys 2017