Letter to the Editor: Patient-reported outcomes of intensity-modulated radiotherapy vs three-dimensional conformal radiotherapy in prostate cancer

Abstract

In this study, published in the World Journal of Clinical Oncology by Mera et al, three-dimensional conformal radiotherapy and intensity-modulated radiotherapy were assessed with respect to patient-reported outcome measures in patients with localized prostate cancer. Furthermore, they used a prospective observational design and analyzed urinary, gastrointestinal, sexual, and quality-of-life end points using real-world outcomes, as opposed to dose-volume histograms or clinician-based toxicity scales. They use the patient-reported outcome measures to show how patients perceive radiotherapy technique, fractionation, dose escalation, and technology.

Key Words: Prostate cancer; Radiotherapy; Intensity-modulated radiotherapy; Three-dimensional conformal radiotherapy; Patient-reported outcome measures

Core Tip: The study by Mera et al demonstrates that patient-reported outcome measures provide crucial information regarding the impact of radiotherapy planning techniques on patients with localized prostate cancer. Comparing three-dimensional conformal radiotherapy and intensity-modulated radiotherapy, the study suggests an association between radiotherapy technique and patient-reported functional outcomes rather than a direct causal relationship. Therefore, patient-reported outcome measures are highly important tools for evaluating treatment and technological advancements from a patient-centered perspective.

TO THE EDITOR

I am pleased to read the high-quality article by Mera et al[1], published in the World Journal of Clinical Oncology. The authors present a comprehensive observational analysis with long-term follow-up, comparing three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) in patients with localized prostate cancer, with outcomes assessed using patient-reported outcome measures (PROMs). Using five-year real-world PROM follow-up data, the study provides an important framework for evaluating how technological advancements in radiotherapy translate into patient-reported functional outcomes. Importantly, this study highlights the clinical significance of interventional factors such as imaging guidance, fractionation strategy, and dose escalation in influencing changes in urinary, bowel, and sexual quality of life.

PATIENT-REPORTED OUTCOMES of IMRT VERSUS 3D-CRT in PROSTATE CANCER

In radiation oncology, evaluating technological innovations based solely on dosimetric measures or clinician-reported toxicity is insufficient. A more comprehensive approach that incorporates patient assessment and interpretation is necessary. PROMs, which directly reflect the impact of treatment on side effects, functional status, and quality-of-life from the patient’s perspective, play an increasingly important role in assessing the impact of technology on treatment outcomes[2,3]. In their article, Mera et al[1] address this critical issue by conducting a long-term observational study comparing 3D-CRT and IMRT in patients with localized prostate cancer using validated PROM instruments.

Prostate cancer is the second most common cancer in men[4]. The 5-year and 15-year survival rates are 98% and 97%, respectively, primarily due to increased screening and earlier diagnosis before symptom development. Notably, 83% of men are diagnosed with localized or regional-stage disease[4].

In prostate cancer, where screening is accessible and diagnosis often occurs at an early stage – resulting in long survival – both oncological outcomes and treatment-related toxicities are becoming increasingly important. Achieving cancer control at the cost of lifelong toxicity that compromises quality of life is not an appropriate approach. Therefore, PROMs are gaining increasing importance.

In the study conducted by Mera et al[1], 92 patients treated with 3D-CRT and 106 patients treated with IMRT were included and followed for five years to evaluate both acute and chronic treatment-related side effects. The aim of the study was to investigate how technological changes in radiotherapy planning affect patients. However, because the comparison was based on a prospective observational design, potential confounding factors – such as patient selection, baseline characteristics, use of androgen deprivation therapy, imaging guidance, planning margins, and differences in dose or fractionation schedules – should be considered when interpreting the PROM outcomes.

Among patients treated with IMRT, 56.6% received hypofractionated schedules, with a mean equivalent dose to the clinical target volume of 77.7 Gy (range: 72.5-88.3). After a five-year follow-up, PROMs were available for 87.2% of patients, and analyses were based on these data.

Although urinary tract-related side effects were more frequent in the IMRT group during the first 12 months, they were less common after 48 months. The increase in early irritative/obstructive symptoms observed in the IMRT group may be related to the higher biological doses administered in the IMRT group and the use of hypofractionated regimens. However, this early deterioration appears to be followed by significant improvement over time, resulting in a lower long-term symptom burden. This two-phase pattern suggests that early urinary symptoms largely reflect transient inflammatory effects, whereas improved dose distribution and better protection of critical urinary structures with IMRT contribute to long-term functional improvement. IMRT, particularly when combined with image-guided radiotherapy applications and smaller planning margins, may therefore offer advantages in preserving long-term urinary function[5]. Nevertheless, differences in treatment era, dose-escalation strategies, fractionation regimens, and concurrent or subsequent therapies may also influence patient-reported outcomes and should be considered when interpreting associations between treatment techniques and functional outcomes.

The HYPRO randomized trial demonstrated that hypofractionated radiotherapy with 3.4 Gy/fraction increased acute genitourinary toxicity compared with conventional fractionation. Patient-reported outcomes from the study conducted by Mera et al. similarly showed a higher incidence of urinary symptoms during treatment and in the early post-treatment period. Consistent with the literature, doses ≥ 3 Gy/fraction and equivalent dose > 78 Gy were associated with worsening of irritative/obstructive urinary symptoms after 12 months, suggesting that early urinary toxicity is driven more by dose and fractionation than by the IMRT technique itself[6,7].

The study observed an increasing proportion of patients reporting declines in sexual function scores and erectile function over time in both the 3D-CRT and IMRT cohorts. This finding aligns with previous reports indicating that radiotherapy may adversely affect periprostatic structures and erectile function, with long-term erectile dysfunction frequently reported among prostate cancer survivors[8]. However, its occurrence in both groups suggests a technique-independent, time-related and age-related effect.

The recovery pattern observed following early deterioration in bowel function is consistent with the literature[9]. This early deterioration can be explained by the healing of acute mucosal damage and inflammation caused by radiation, supported by the high regenerative capacity of the intestinal epithelium. Mucosal regeneration and tissue adaptation contribute to symptom reduction, particularly when late structural damage is limited.

In the IMRT group, the frequency of rectal bleeding was lower after 24 months. IMRT reduces the radiation dose delivered to the rectum, leading to decreased long-term gastrointestinal toxicity[10]. The low incidence of loss of bowel control in both groups further reflects the protective effects of modern radiotherapy techniques on anorectal function.

In cancers such as prostate cancer, which are diagnosed early and associated with long survival, evaluating treatment success solely on tumor control or clinician-reported toxicity is insufficient. A key determinant in this patient group is how treatment affects their daily lives, functional capacity, and long-term quality of life. PROMs capture these effects directly from the patient perspective, revealing dimensions that conventional assessment tools may overlook. This enables a shift from a purely technical assessment toward a more patient-centered approach focused on quality of life.

While technological advancements and their effects in radiotherapy are often defined by dose distribution and planning parameters, their true value can only be understood through patient experience. Even when clinician-reported toxicity appears similar, patients may experience substantial differences in symptom burden, functional impairment, and psychological adaptation. PROMs uncover these subtle but clinically significant differences and help determine whether a technically successful treatment is also successful from the patient’s perspective.

In prostate cancer radiotherapy in particular, it is crucial to clearly distinguish between early, transient toxicities and late effects that may be permanent and progressive. PROM-based assessments allow for longitudinal evaluation of symptom trajectories, helping to determine whether treatment-related effects are reversible or persistent. In this sense, PROMs are not only outcome measures but also dynamic tools that guide the optimization of treatment strategies.

CONCLUSION

In conclusion, a clear understanding of PROMs is an important step toward more personalized treatment. PROM-based evaluations can support individualized therapeutic approaches and improve understanding of how radiotherapy techniques influence long-term quality-of-life outcomes.