Developing robust indicators to measure treatment-related side-effects following prostate cancer treatment.

Arunan Sujenthiran, NPCA Clinical fellow and Urology Specialist Registrar

During the NPCA’s Quality Improvement workshop we described the journey we have taken over the last few years to investigate some common side-effects that can occur following prostate cancer treatment. This is a key priority for the NPCA as we know many men live with the consequences of their prostate cancer treatment for many years, even once their cancer is cured.

The NPCA evaluates common side-effects (urinary and bowel) following surgery (radical prostatectomy) and radiotherapy. During the Quality Improvement workshop we explained how we developed “treatment-related indicators” to capture these side-effects; and then how these “indicators” have been used to compare providers and to evaluate newer treatments.

Indicator Development & Validation

Within the NPCA we have linked large data sets related to patient, disease and treatment characteristics in a partnership with our data sharing partners. One of these data sets, Hospital Episodes Statistics (HES), is an administrative dataset that includes both procedural codes (OPCS-4) and diagnostics codes (ICD-10). We developed and validated treatment-related toxicity indicators, primarily based on these codes, to capture severe urinary and bowel side-effects following radical treatment. During the presentation we highlighted steps taken by the NPCA team to ensure these indicators were transparent and robust in their methodology (1).

Patient-reported outcome measures (PROMs)

The NPCA has also carried out a Patient Survey to determine men’s views of their outcomes following treatment, including questions about their quality of life and sexual/urinary/bowel functioning. Questionnaires were sent to all men who received or were candidates for radical treatment. The workshop audience was encouraged by the excellent patient engagement achieved with almost three quarters of men (73%) responding. Answers from the questionnaire were used to generate validated scores (from the EPIC-26 scale) representing urinary incontinence and sexual function after radical prostatectomy, and bowel and sexual function after radiotherapy.

Evaluation of treatment modalities

These indicators have been used to assess variation across NHS centres and to evaluate newer surgical and radiotherapy treatments. The first study evaluated the three techniques used to perform radical prostatectomy. The robotic approach has been rapidly adopted in the UK without robust evidence on functional outcomes compared to the previous standard of open or laparoscopic surgery. Using our treatment-related toxicity indicators, on the basis of routine data, we showed that robotic-assisted radical prostatectomy resulted in significantly less urinary toxicity than either laparoscopic or open radical prostatectomy. We found specifically that “stricture-related” toxicity was lower after robotic-assisted radical prostatectomy (2).

We also compared functional outcomes reported by men undergoing the different surgical modalities. We found that robotic-assisted radical prostatectomy was associated with slightly higher sexual function scores (an increase of 3.5 points on a scale of 0-100) compared with the open approach but this did not meet the threshold for a clinically meaningful change, suggesting that most patients would not identify this difference as important. There were no differences in urinary or bowel function scores between the surgical modalities (3).

We also investigated treatment-related toxicity comparing 3D-conformal radiotherapy (3D-CRT) with intensity-modulated radiotherapy (IMRT) in both the primary and post-prostatectomy settings. In the primary setting, IMRT resulted in significantly less urinary toxicity and similar bowel toxicity (4). In the post-prostatectomy setting however, we found no difference between IMRT and 3D-CRT in terms of urinary and bowel toxicity (5). Given IMRT is now widely used in the UK, these studies supported current practice though raised questions about the benefit of IMRT in the post-prostatectomy setting.

Further work has compared treatment-related toxicity using ‘prostate-only’ versus ‘prostate and pelvic lymph node’ IMRT. In this study we found that there was no significant difference in urinary and bowel toxicity between the two groups (6). We therefore recommended that pelvic lymph node irradiation should be considered in the high-risk population.

The final study we presented was a comparison of hypofractionated and conventionally fractionated radiotherapy. There has been a transition to hypofractionation in the UK but toxicity remains uncertain in older men and locally advanced disease. Using our real-world data sets we were able to evaluate this and found no difference in severe urinary and bowel toxicity with hypofractionation (7). We found similar results when PROMs were used to compare the groups, which further supports the use of hypofractionation as the standard for radiotherapy in men with non-metastatic prostate cancer (8).

The session was concluded by discussing some of the future research work the NPCA will be working on including the effect of high dose-rate (HDR) brachytherapy boost on toxicity and outcomes of other prostate cancer treatment modalities such as focal therapy. This was followed by questions from the audience who were interested in the indicators used as well as the breadth of research questions we have answered using real-world data.

There was lively discussion regarding the importance of nationally collected PROMs as part of the NPCA to inform treatment decision making and quality improvement.

1) Sujenthiran A, Charman SC, Parry M, et al. Quantifying severe urinary complications after radical prostatectomy: the development and validation of a surgical performance indicator using hospital administrative data. BJU Int. 2017;120(2):219‐225.

2) Sujenthiran A, Nossiter J, Parry M, et al. National cohort study comparing severe medium-term urinary complications after robot-assisted vs laparoscopic vs retropubic open radical prostatectomy. BJU Int. 2018;121(3):445‐452.

3) Nossiter J, Sujenthiran A, Charman SC, et al. Robot-assisted radical prostatectomy vs laparoscopic and open retropubic radical prostatectomy: functional outcomes 18 months after diagnosis from a national cohort study in England. Br J Cancer. 2018;118(4):489‐494.

4) Sujenthiran A, Nossiter J, Charman SC, et al. National Population-Based Study Comparing Treatment-Related Toxicity in Men Who Received Intensity Modulated Versus 3-Dimensional Conformal Radical Radiation Therapy for Prostate Cancer. Int J Radiat Oncol Biol Phys. 2017;99(5):1253‐1260.

5) Sujenthiran A, Nossiter J, Parry M, et al. Treatment-related toxicity in men who received Intensity-modulated versus 3D-conformal radiotherapy after radical prostatectomy: A national population-based study. Radiother Oncol. 2018;128(2):357‐363.

6) Parry MG, Sujenthiran A, Cowling TE, et al. Treatment-Related Toxicity Using Prostate-Only Versus Prostate and Pelvic Lymph Node Intensity-Modulated Radiation Therapy: A National Population-Based Study. J Clin Oncol. 2019;37(21):1828‐1835.

7) Sujenthiran A, Parry M, Nossiter J, et al. Comparison of Treatment-Related Toxicity With Hypofractionated or Conventionally Fractionated Radiation Therapy for Prostate Cancer: A National Population-Based Study [published online ahead of print, 2020 Mar 3]. Clin Oncol (R Coll Radiol). 2020;S0936-6555(20)30044-3.

8) Nossiter J, Sujenthiran A, Cowling TE, et al. Patient-Reported Functional Outcomes After Hypofractionated or Conventionally Fractionated Radiation for Prostate Cancer: A National Cohort Study in England. J Clin Oncol. 2020;38(7):744‐752.

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Last updated: 9 November 2020, 10:38pm