PROSPECT Echoes – the Power of Words and the Importance of the Chosen Perspective

“Nothing in life is to be feared, it is only to be understood.
Now is the time to understand more, so that we may fear less.”
Marie Sklodovska-Curie

 

Limited awareness and negative perceptions

Radiation Oncology is not new as a medical field, but it is not well known, either. Its unique combination of clinical and technical aspects makes it look like a “foreign realm” for many other specialties. When it comes to the general public, the fog might be even thicker. A survey on public awareness in the UK showed that approximately 40% of respondents had negative perceptions about radiotherapy [1]. Information related to nuclear weapons, power plant accidents or second hand experiences enhance the negative connotations linked to the term “radiation”, increasing patients’ anxiety, which may lead to treatment delay or refusal. An Australian survey on more than 1100 oncology patients concluded that concerns on side effects and their management influenced the decision to reject radiotherapy [2]. The impact on fertility and misperceptions about becoming radioactive represent other frequent issues perceived by patients [3].

Especially in the context of expanded availability of information through online channels and increasingly  recognized patients’ role in shared treatment decisions, accurate and balanced information regarding treatment options becomes crucial.

The other side of the coin

The recent results of the PROSPECT trial received a lot of attention, and not only from scientists or clinicians [4]. Major publications targeting the general public presented interpretation and comments on the data presented at ASCO 2023 [5]. The trial compared the standard treatment for locally advanced rectal cancer (pre-operative radiation therapy combined with low-dose single agent chemotherapy) with 6 cycles of multiagent chemotherapy (FOLFOX). It was hypothesized that chemotherapy alone is not inferior to radiochemotherapy, so this option can be an alternative to chemoradiation in selected patients. What mass media presented might have been interpreted as a story in which multi-agent chemotherapy is the hero, while radiotherapy being the villain.

The unbalanced perspective could not pass unnoticed by the radiation oncology community and official statements were published by professional societies [6] [7]. Despite the subsequent rephrasing on publications’ websites and giving up on catchy terms like “brutal radiotherapy”, the main message remains and will probably impact some of the patients’ opinion. As a result, healthcare professionals need to be up to date and able to discuss with the patients the pros and cons of all existent options.

Some relevant aspects that were underlined in the ASTRO and ESTRO statements related to the PROSPECT trial are briefly mentioned below.

  • Oncological outcomes – similar in both arms;
  • Toxicity – the rate of significant side effects was actually higher on the chemotherapy group compared to the radiochemotherapy group (41% vs 23%) The increased toxicities in the chemotherapy arm included anxiety, appetite loss, constipation, depression, difficulty swallowing, shortness of breath, edema, fatigue, mouth sores, nausea, vomiting and neuropathy;
  • Quality of life – overall health related quality of life was similar at any time point, only in a few domains significantly worse for radiochemotherapy at 18 months;
  • Long term toxicity and quality of life data – not reported, despite the median follow-up of 58 months;
  •       Other observations

o Radiotherapy was needed in 10% of the patients from the chemotherapy arm;

o Some of the patients with small tumors might have been overtreated in both arms. According to the European guidelines the cT3a-T3b N0 tumors of the middle and upper rectal third might be treated with surgery alone;

o The cT3 subgroups were not reported and 15% of the patients did not have baseline staging MRI;

o Some of the toxicity in the radiochemotherapy arm depend on the combination of surgery and radiotherapy.

While appreciating the effort of all participants in the trial and the importance of its results, a well balanced interpretation is needed for taking adapted decisions. This new option in the therapeutic approach of rectal cancer comes with both advantages and disadvantages, so the choice can be made according to patients’ personal priorities regarding the specific toxicity profile.

Fighting on several fronts

Identifying new solutions for avoiding toxicity, while keeping the efficacy, is one of the main current objectives in cancer care and the PROSPECT trial is part of this endeavor. The multimodality management of rectal cancer shifts towards solutions for avoiding rectal excision, which can be achieved for up to 80% for early stages and up to 50% in advanced stages, radiotherapy being an essential component in this approach.

It is worth mentioning that radiotherapy toxicity significantly decreased due to technological improvements. A pooled analysis of 859 patients concluded that IMRT reduced grade ≥2 and grade ≥3 acute gastrointestinal and grade ≥2 genitourinary toxicities in rectal cancer patients treated with preoperative chemoradiation, compared to 3D CRT. For example, overall acute gastrointestinal toxicity  decreased from 54.5% to 29.1% for grade ≥2  and from 8.9% to 2.6% for grade ≥3 [8]. However, increased precision in delivery needs increased precision and consistency in contouring. It was already shown that for many anatomical sites, including rectal cancer, interobserver variations impact the planning and dosimetry, so they ultimately impact the patients. Following contouring guidelines decrease this variation, the impact being even higher for high conformal techniques [9].

To address this need, new technologies are continuously developed, including AI based auto-contouring. When taking these tools in clinical use, it is imperative to make sure that the AI based contours are precisely following the contouring guidelines, so as not to create systematic errors and to guide the clinicians towards the correct consensus.

In summary, in order to provide the best care for our patients we need to be aware of the new research results, interpret them wisely, assess patients’ perception, inform them correctly, share the treatment decision and deliver the adapted therapy with adequate solutions.

 

References

[1] James S: A guide to modern radiotherapy. London, United Kingdom, Society and College of Radiographers, 2013.

 

[2] Sundaresan P, King M, Stockler M, Costa D, Milross C. Barriers to radiotherapy utilization: Consumer perceptions of issues influencing radiotherapy-related decisions. Asia Pac J Clin Oncol. 2017;13(5):e489-e496. doi:10.1111/ajco.12579

 

[3] Gillan C, Abrams D, Harnett N, Wiljer D, Catton P. Fears and misperceptions of radiation therapy: sources and impact on decision-making and anxiety. J Cancer Educ. 2014;29(2):289-295. doi:10.1007/s13187-013-0598-2

 

[4] Schrag D, Shi Q, Weiser MR, et al. Preoperative Treatment of Locally Advanced Rectal Cancer [published online ahead of print, 2023 Jun 4]. N Engl J Med. 2023;10.1056/NEJMoa2303269. doi:10.1056/NEJMoa2303269

 

[5] https://www.nytimes.com/2023/06/04/health/rectal-cancer-radiation-treatment.html

 

[6] https://www.estro.org/About/Newsroom/News/PROSPECT-trial-adds-another-treatment-possibility

 

[7] https://www.astro.org/News-and-Publications/News-and-Media-Center/News-Releases/2023/ASTRO-GI-panel-responds-to-PROSPECT-clinical-trial

 

[8] Wee CW, Kang HC, Wu HG, et al. Intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy in rectal cancer treated with neoadjuvant concurrent chemoradiation: a meta-analysis and pooled-analysis of acute toxicity. Jpn J Clin Oncol. 2018;48(5):458-466. doi:10.1093/jjco/hyy029

 

[9] Lobefalo F, Bignardi M, Reggiori G, et al. Dosimetric impact of inter-observer variability for 3D conformal radiotherapy and volumetric modulated arc therapy: the rectal tumor target definition case. Radiat Oncol. 2013;8:176. Published 2013 Jul 9. doi:10.1186/1748-717X-8-176

 

 

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