Cost-Effectiveness Analysis of Radiotherapy Versus Prostatectomy in Prostate Imaging Reporting and Data System (PI-RADS) 5 Prostate Cancer Using Reconstructed Survival Data and Economic Modelling

Simple Summary

This study compares the cost-effectiveness of radical prostatectomy versus radiotherapy combined with androgen deprivation therapy in patients with PI-RADS 5 prostate cancer. Using survival data reconstructed from two retrospective cohorts, the authors generated Kaplan–Meier curves, conducted a comparative metasurvival analysis, and built a cost model to evaluate clinical outcomes and economic impact. Radiotherapy showed markedly better biochemical recurrence-free survival at five years (83% vs. 28%), a higher survival curve AUC (80.7 vs. 41.9), and a substantially lower cost per recurrence-free patient (€21,211 vs. €113,730). Overall, radiotherapy plus ADT appears to be a more cost-efficient option than radical prostatectomy in this high-risk population, though prospective validation is needed.

Abstract

Introduction. This study aims to conduct a cost-effectiveness analysis comparing two primary treatment approaches: radical prostatectomy versus radiotherapy plus androgen deprivation therapy (ADT) in patients with Prostate Imaging Reporting and Data System (PI-RADS) 5 lesions. Patients and Methods. Data were extracted from two published retrospective cohort studies. Using survival data from two retrospective studies, we reconstructed Kaplan–Meier curves, overlaid them for comparative metasurvival analysis, and developed a cost-function model to assess economic implications alongside clinical outcomes. The primary outcomes included biochemical recurrence-free survival (FFBF) at 2 and 5 years; the area under the survival curve; total cost per treatment strategy; and cost per recurrence-free patient at 5 years. Results. At 5 years, the estimated FFBF was 83% for radiotherapy vs. 28% for prostatectomy. Radiotherapy yielded an AUC of 80.7, while prostatectomy showed 41.9. Radiotherapy yielded a cost of 21,211 € per FFBF patient compared to 113,730 € for prostatectomy. Conclusion. Our study demonstrates that radiotherapy combined with ADT, when selected based on mpMRI stratification, may represent a cost-efficient alternative, pending prospective validation. To radical prostatectomy in patients with PI-RADS 5 prostate cancer, with a favourable cost–benefit profile.

1. Introduction

Prostate cancer represents one of the most prevalent malignancies in men, with localised disease often amenable to curative-intent therapies such as radical prostatectomy or radiotherapy. The emergence of multiparametric magnetic resonance imaging (mpMRI) and the Prostate Imaging Reporting and Data System (PI-RADS) scoring system has significantly improved risk stratification [1,2,3,4,5,6,7,8,9,10,11]. PI-RADS 4 (p = 0.045) and PI-RADS 5 (p < 0.001) lesions were also significantly associated with a higher risk of clinically significant prostate cancer (Gleason score ≥ 3 + 4) [12].

In a retrospective analysis, Mistretta et al. [13] reported data on 606 patients with prostatic cancer enrolled in their active surveillance programme. PSAd ≥ 0.15 (HR: 1.43; p = 0.04), PI-RADS 4–5 (HR: 2.56; p < 0.001) and number of biopsy-positive cores ≥ 2 (HR: 1.75; p < 0.001) were independent predictors of active surveillance exit at multivariable Cox regression models. Authors concluded that conditional survival models showed a direct relationship between event-free survival duration and subsequent active surveillance persistence in overall prostate cancer patients, as well as after stratification by risk category.

Fazebas et al. [14] conducted a systematic review and meta-analysis to assess the effectiveness of integrating multiparametric magnetic resonance imaging (mpMRI) into prostate cancer screening pathways. Their findings demonstrated that adopting a PI-RADS threshold of ≥4 for biopsy selection was associated with a significant reduction in the likelihood of detecting clinically insignificant prostate cancer (OR = 0.23; 95% CI: 0.05–0.97; p = 0.048), as well as a decrease in the overall number of biopsies performed (OR = 0.19; 95% CI: 0.09–0.38; p = 0.01). Importantly, these improvements did not come at the cost of reduced detection of clinically significant prostate cancer (OR = 0.85; 95% CI: 0.49–1.45; p = 0.22). In summary, the authors concluded that the integration of magnetic resonance imaging into prostate cancer screening protocols reduces the number of unnecessary biopsies and the overdiagnosis of clinically insignificant disease, while maintaining comparable detection rates for clinically significant prostate cancer when compared with PSA-only screening strategies.

An additional key consideration concerns the prostatic zonal anatomy, as the peripheral zone is histologically distinct from the transitional zone, a factor that significantly influences lesion distribution and malignancy detection.

In this context, Rodríguez-Cabello et al. [15] presented the results of a cross-sectional study including 597 men evaluated for suspected prostate cancer, of whom 473 were ultimately included, accounting for a total of 573 biopsied lesions (127 PI-RADS 3, 346 PI-RADS 4, and 100 PI-RADS 5). The authors reported a significant increase in both lesion proportion and malignancy in peripheral-zone samples compared with transitional-zone samples. Specifically, malignancy rates were 37.3% vs. 23.7% for PI-RADS 4 lesions and 69.2% vs. 27.3% for PI-RADS 5 lesions, respectively. These findings underscore the importance of considering prostatic zonal differences when interpreting PI-RADS scores and planning targeted biopsy strategies.

Patients with a PI-RADS score of 5 represent a particularly high-risk cohort due to their elevated likelihood of harbouring clinically significant, aggressive disease [16]. In addition to a PI-RADS score of 4–5, both the maximum diameter of the index lesion and the presence of extracapsular extension and/or seminal vesicle invasion have been identified as strong predictors of biochemical recurrence in patients undergoing radical prostatectomy. Consequently, mpMRI-based predictive models have demonstrated accuracy comparable to validated postoperative models that rely on final pathological findings in predicting biochemical recurrence. Furthermore, incorporating mpMRI-derived parameters to predict disease recurrence following radiotherapy or focal therapy appears to enhance post-treatment patient risk stratification, facilitating the exclusion of recurrence and improving individualised clinical management [17]. For this reason, we intentionally focused only on PI-RADS 5 lesions to analyse a biologically and clinically homogeneous population at high risk of requiring definitive treatment. Including PI-RADS 3–4 would have introduced significant heterogeneity in risk, treatment indication and prognosis.

Recently, a meta-analysis (18,745 prostate cancer cases) has demonstrated that the PI-RADS score is an independent factor predicting Gleason score upgrading following radical prostatectomy [18].

Collectively, these studies underscore the clinical utility of mpMRI not only in improving the diagnostic pathway for prostate cancer but also in informing prognostic assessment and post-treatment risk stratification. Parameters such as PI-RADS score, lesion size, zonal location, and evidence of extracapsular extension consistently emerge as key factors influencing both the likelihood of recurrence and the planning of individualised treatment strategies.

Despite this, comparative data on treatment effectiveness and cost-efficiency for this subgroup remain sparse. This study aims to address this gap by conducting a cost-effectiveness analysis comparing two primary treatment approaches: radical prostatectomy versus radiotherapy plus androgen deprivation therapy (ADT) in patients with PI-RADS 5 lesions.

2. Patients and Methods

Data were extracted from two published retrospective cohort studies: Fiard et al. [19] for the prostatectomy arm and Turchan et al. [20] for the radiotherapy arm (Table 1).

Table 1. Comparison of prostatectomy vs. radiotherapy across the two studies considered.

Authors	Regimens	N° Patients PI-RADS 5	Median FU (Months)	MFS (%)
Fiard et al. [19]	surgery	539	25	92 *
Turchan et al. [20]	radiotherapy	54	67	82 **

Legend: N° = number; PI-RADS = Prostate Imaging Reporting and Data System; FU = follow-up; MFS = metastases-free survival; * = estimated at 2 years; ** = estimated at 7 years.

Because data were available only in aggregated form, no clinical covariates (e.g., PSA, stage, ISUP grade, comorbidities) could be adjusted for, and individual-level matching was not feasible. Therefore, residual confounding between cohorts cannot be excluded.

To standardise the economic comparison, an incremental cost-effectiveness ratio (ICER) was calculated as the difference in expected costs divided by the difference in recurrence-free survival, expressed as area under the curve (AUC):

$$ICER={\displaystyle \frac{Cost\left(RT+ADT\right)-CostRP}{2aAUC\left(RT+ADT\right)-AUCRP}}$$

AUC was used as a proxy for mean recurrence-free survival when QALY or utility weights were unavailable [21].

Kaplan–Meier curves from the included studies did not provide patient-level data. For this reason, survival points were digitised using GetData Graph Digitiser (GetData Pty Ltd., Montgomery, Australia, version 2.26.0.20), with the axes calibrated and survival probability values extracted at regular 0.1-month intervals. The extracted coordinates were then processed to reconstruct the survival function of each cohort. Reconstruction quality was assessed through visual overlap between the published and reconstructed curves, as well as by verifying that the difference in median survival between the original and reconstructed curves remained below 5%.

After reconstruction, the survival trajectories of the two cohorts were overlaid to allow direct comparison over a standard time axis, and the area under the curve (AUC) was calculated to estimate the cumulative recurrence-free time. To compare survival without restricting the analysis to a fixed time point (e.g., 24 or 60 months), a pooled survival curve was estimated from the reconstructed data. For this purpose, we applied the nonparametric framework described by Combescure et al. [22], which extends the Kaplan–Meier estimator to aggregated datasets. Each study contributes conditional survival probabilities across its follow-up period. At the same time, a random-effects model is used to account for differences in follow-up duration, censoring patterns, and sample size. Between-study heterogeneity was estimated using the multivariate DerSimonian–Laird method, the reference approach for random-effects meta-analysis. This method presents several advantages:

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it does not impose a predefined parametric shape on the survival curve,

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all studies contribute information, even those with shorter follow-up,

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The resulting pooled curve is guaranteed to be monotonically decreasing, consistent with biological expectations.

All statistical analyses and graphical output were performed using the R Statistical Computing Environment (R Foundation for Statistical Computing, Vienna, Austria).

To quantify the cumulative benefit, we calculated the AUC from the survival trajectories. The costs of radical prostatectomy (€5000) and radiotherapy (€4000) were derived from the Italian National Health System reimbursement tariffs. The monthly cost of androgen deprivation therapy (ADT) (€239/month) was obtained from the AIFA national reimbursed price list. The economic model adopted a 5-year time horizon, consistent with the follow-up duration of the included studies. Both costs and recurrence-free survival were discounted at an annual rate of 3.5%, in accordance with European pharmacoeconomic guidelines (EUnetHTA/EMA). Cost inputs included 5000 euros (€) for prostatectomy, 4000 € for radiotherapy and 239 € per month for ADT.

ADT was administered for 24 months in the radiotherapy group and lifelong upon recurrence in both groups. Recurrence rates were extracted from the respective studies (17% for radiotherapy and 72% for prostatectomy).

Two expert reviewers independently assessed selected studies in the systematic search (JG and FF). The primary outcomes included: biochemical recurrence-free survival (BRFS) at 2 and 5 years, the area under the survival curve (AUC), total cost per treatment strategy, and cost per recurrence-free patient at 5 years.

Because patient-level utilities and transition probabilities were unavailable in the included studies and no quality-of-life data were provided, traditional Markov modelling was not feasible. Therefore, the survival benefit was quantified using the area under the survival curve (AUC), which reflects the cohort’s mean survival time. This approach has been described as an acceptable proxy when utilities are unavailable and survival is the primary outcome of interest [23,24,25].

3. Results

A total of 96 patients with PI-RADS 5 lesions were included (radiotherapy + ADT: n = 54; radical prostatectomy: n = 42). Baseline characteristics of the two cohorts are summarised in Table S1.

At 2 years, the estimated FFBF was 95% for radiotherapy and 54% for prostatectomy. At 5 years, this advantage persisted with FFBF rates of 83% versus 28%, respectively (Figure 1).

Figure 1. Superimposed Kaplan–Meier Curves: PI-RADS 5.

Using the area under the survival curve (AUC) as a measure of cumulative recurrence-free survival time, radiotherapy plus ADT yielded 80.7 recurrence-free patient-months, whereas prostatectomy yielded 41.9, resulting in 38.8 more recurrence-free months in favour of radiotherapy.

From a cost perspective, the initial treatment cost for radiotherapy, including 24 months of ADT, was estimated at 9736 €. Considering a 17% recurrence rate and an additional 28,680 € cost for 10 years of ADT upon recurrence, the total expected cost rises to 11,198 €. Conversely, prostatectomy starts with a lower base cost of 5000 €. However, the significantly higher recurrence rate of 72% results in a substantial burden of salvage ADT, bringing the total estimated cost to 11,195 €.

When applying a lifetime cost model that accounts for the full cost of ADT per recurrent case, the financial burden escalates to 17,604 € for radiotherapy and 31,844 € for prostatectomy (Figure 2). This model reflects the chronic and compounding nature of disease relapse, particularly in the surgical cohort.

Figure 2. Economic comparison of prostate cancer treatment strategies.

The most striking difference lies in the cost per recurrence-free patient at 5 years. Radiotherapy yost o1211 € per FFBF patient, compared to 113,730 € for prostatectomy.

Sensitivity Analysis

A one-way sensitivity analysis was conducted to assess the robustness of the economic model by independently varying key parameters, including recurrence rates (±20%), ADT duration in the radiotherapy arm (12–36 months), and unit treatment costs (±30%). As illustrated in Figure 3, the model proved particularly sensitive to changes in ADT duration and the recurrence rate following radical prostatectomy, both of which produced the largest fluctuations in the ICER estimates.

Figure 3. Tornado plot of one-way sensitivity analysis for ICER.

Despite these variations, radiotherapy combined with ADT consistently maintained a favourable cost-effectiveness profile. Notably, in several plausible scenarios, radiotherapy became the dominant strategy, offering both lower overall cost and greater recurrence-free survival compared with prostatectomy. The full range of ICER values for each parameter examined in the sensitivity analysis is provided in Table S1.

4. Discussion

The rising costs of cancer care, particularly the cost of treatments that produce only marginal benefits, are increasingly under scrutiny. While healthcare professionals shy away from assigning a value to life, our limited resources require society to address questions about what constitutes a benefit, how much cost should be considered in decision-making, and who should be involved in these decisions. Professional societies, government agencies, and insurance companies should be involved. However, no segment of society is better qualified than the oncology community to address these issues. Therefore, oncology professionals should offer clear guidance for conducting research, interpreting results, and choosing/prescribing treatments.

The findings from this analysis suggest a potential advantage of radiotherapy with ADT as a cost-effective strategy for the management of PI-RADS 5 prostate cancer.

Patients receiving radiotherapy + ADT had more unfavourable disease characteristics at baseline (higher PSA, higher proportion of ≥T3 and Gleason ≥ 8 disease), suggesting that the worse oncologic outcomes observed after surgery cannot be explained by a more aggressive selection in the radiotherapy cohort (Table S1).

We acknowledge that using AUC as a surrogate for QALYs is unconventional. This choice was dictated by the absence of utility measures and transition states in the source datasets, which prevented the construction of a state-transition (Markov) model. As such, results should be interpreted as hypothesis-generating rather than definitive cost-effectiveness estimates.

Given the retrospective nature of the source studies and the use of aggregated data, this analysis should be considered exploratory. It cannot be generalised to the entire prostate cancer population. The conclusions apply only to patients with PI-RADS 5 lesions and should be considered hypothesis-generating.

The conclusions apply only to patients with PI-RADS 5 lesions and should be considered hypothesis-generating. Because survival data were reconstructed from published Kaplan–Meier curves, patient-level variables (comorbidities, age, surgical technique, radiotherapy dose, duration and type of systemic therapy) could not be controlled for, and residual confounding is possible. Propensity score matching, which requires individual-level patient data, was not feasible because both datasets reported only aggregated variables.

By integrating clinical outcome data with economic modelling and aligning the survival curves from two independent retrospective studies, we were able to compare treatment strategies not only in terms of efficacy but also in terms of economic sustainability.

Radiotherapy was associated with higher recurrence-free survival in the available data across all examined time points, with an absolute advantage of 38.8 patient months of recurrence-free survival (RFS) over prostatectomy. These differences were especially evident within the first 2 to 3 years, indicating earlier and more frequent recurrence in the surgical cohort. This finding has important clinical implications: early biochemical failure often necessitates a shift to salvage therapies such as radiotherapy and chronic ADT, exposing patients to additional treatments, potential toxicities, and emotional burdens.

While the long-term overall survival rates between the two strategies may eventually converge, the therapeutic trajectories are different. Patients undergoing surgery are more likely to require early salvage interventions, necessitating an escalation pathway. This finding could contribute not only to cumulative healthcare costs but also to patient morbidity and decreased quality of life. In contrast, the radiotherapy pathway, particularly when guided by mpMRI risk stratification, could enable more durable disease control and avoid unnecessary escalation in the majority of patients, a clinically meaningful metric suggesting a longer duration of disease control without the need for salvage interventions.

From an economic standpoint, although the initial costs of radiotherapy are higher due to upfront ADT, the overall long-term cost is significantly lower when accounting for recurrence and subsequent lifelong hormone therapy. The cost per patient who remained recurrence-free at 5 years was approximately 5 times lower with radiotherapy than with surgery. This fivefold difference in efficiency emphasises how improved disease control with radiotherapy could directly translate into better resource utilisation. This metric, simple, reproducible, and clinically meaningful, offers a powerful tool for evaluating treatment value.

Moreover, mpMRI plays a central role in patient selection. The ability to non-invasively identify patients at the highest risk of progression enables the optimised allocation of intensive treatment strategies, such as combination radiotherapy and ADT. This precision-based approach enhances not only clinical outcomes but also the overall efficiency of care delivery. In the era of personalised medicine, stratifying patients based on radiologic markers, such as PI-RADS 5, supports tailored interventions that minimise overtreatment while maximising benefit for those who need it most.

It is also noteworthy that the observed advantage of radiotherapy persists despite the smaller sample size of the radiotherapy cohort. The robustness of these findings, even when drawn from different institutions with potential differences in practice and baseline characteristics, reinforces their relevance. Notably, the reconstruction of survival curves and the meta-survival overlay analysis enable a direct, time-aligned comparison of outcomes, enhancing the methodological strength of this evaluation.

Nevertheless, our analysis is not without limitations. The primary constraint is the data’s retrospective nature. While both Fiard et al. [19] and Turchan et al. [20] provided robust survival curves, differences in institutional practice, staging accuracy, and follow-up intensity could influence outcomes. Additionally, the numerical imbalance between cohorts (539 patients in the prostatectomy group vs. 54 patients in the radiotherapy group) raises questions about the generalisability of the results. Smaller sample sizes may over- or underestimate variability in clinical outcomes.

Because survival data were reconstructed from published Kaplan–Meier curves, patient-level variables (comorbidities, age, surgical technique, radiotherapy dose, duration and type of systemic therapy) could not be controlled for, and residual confounding is possible.

Furthermore, mpMRI is not yet universally standardised or uniformly implemented across centres. Although our model assumes high diagnostic fidelity, real-world variability in interpretation may impact its predictive accuracy. Future studies should validate our findings prospectively, incorporating standardised mpMRI reporting and harmonised treatment algorithms.

Probably the greatest limit is that the role of radiotherapy in this matter is conflicting. Recently, Miszczyk et al. [26] conducted a retrospective analysis investigating the association between the PI-RADS v2.1 classification and the risk of metastasis in a cohort of 152 patients treated with ultra-hypofractionated stereotactic CyberKnife radiotherapy for localised low- or intermediate-risk prostate cancer. Using a risk stratification model combining the largest lesion dimension, the product of PI-RADS target lesion axial measurements, and patient age, the authors hypothesised that a PI-RADS score of 5 and a larger target lesion size are significant prognostic factors in patients with early-stage prostate cancer. These features, therefore, should be regarded as adverse prognostic indicators in individuals undergoing early therapeutic interventions such as radiation or focal therapy.

However, the study’s retrospective design, limited number of metastatic events, small sample size, and moderate follow-up duration constrain the statistical robustness of the analysis and reduce the overall strength of the conclusions.

A meta-analysis [27] showed that, based on data from 5 studies including 834 patients, active surveillance candidates with PI-RADS 4 or 5 may be unsuitable for active surveillance, even though they fulfil current active surveillance criteria. In contrast, those with PI-RADS 3 or less are considered relatively safe for AS enrolment.

More recently, other authors [28] have presented data of 247 patients with localised prostate cancer treated with prostate stereotactic body radiation therapy (SBRT), with a median of 40 Gy in 5 fractions, evaluated at their institution over 10 years. Patients underwent post-treatment biopsies, with a median time to biopsy of 2.2 years, to evaluate local control. Factors independently associated with post-treatment biopsy outcomes were the presence of a PI-RADS 4 or 5 dominant intra-prostatic lesion (DIL) (OR 6.95, p = 0.001), radiographic T3 disease (OR 5.23, p < 0.001), SBRT dose ≥ 40 Gy (OR 0.26, p = 0.003) and use of androgen deprivation therapy (ADT) (OR 0.28, p = 0.027). Among patients with a DIL (N = 149), the only factors associated with post-treatment biopsy outcomes among patients with a DIL (149 patients) were ≥50% positive cores (OR 2.4, p = 0.037), radiographic T3 disease (OR 4.04, p = 0.001), SBRT dose ≥ 40 Gy (OR 0.22, p < 0.001) and the use of ADT (OR 0.21, p = 0.014). They concluded that men with PI-RADS 4 or 5 DILs have a higher risk of local recurrence after prostate SBRT and that most recurrences are located within the DIL.

Margolese et al. [29] conducted a retrospective analysis of patients treated with radiotherapy at their institution over 10 years, aiming to compare the prognostic significance of the PI-RADS score, index lesion diameter, and the Cancer of the Prostate Risk Assessment (CAPRA) score for predicting biochemical recurrence. A total of 499 patients (33.7% of 1480 total) underwent pre-treatment diagnostic MRI, with 49.5% receiving low-dose brachytherapy, 29.8% treated with external beam radiation therapy (EBRT) combined with a high-dose-rate brachytherapy boost, and 20.7% treated with EBRT alone. Among the MRI cohort, 404 patients (81%) had PI-RADS 4–5 lesions, including 35% with lesions ≥ 15 mm and 20% with lesions ≥ 20 mm. The authors concluded that a lesion diameter ≥ 20 mm on MRI represented an independent prognostic factor for biochemical recurrence, particularly in patients with high-risk prostate cancer.

Comparative effectiveness studies of radical prostatectomy (RP) versus radiotherapy (RT) in prostate cancer overall (not exclusively PI-RADS 5 stratified) provide additional insight. For example, a large population-based Manitoba cohort (2540 RP vs. 1895 RT) found that, after inverse probability weighting, RT was associated with higher all-cause mortality (HR 1.93) and prostate cancer-specific mortality (HR 3.98) compared with RP [30].

Such findings, albeit not PI-RADS-specific, suggest that for men with high-risk disease, surgery may yield superior survival outcomes. Extrapolating to PI-RADS 5 lesions—given their high-risk nature—one might infer that RP could offer a comparative advantage over RT in this subgroup.

In summary, PI-RADS 5 is strongly associated with higher tumour volume, extracapsular extension, and nodal involvement, even at diagnosis. The markedly low 5-year BCR-FS (28%) after RP in one series strongly supports this interpretation. While direct comparative RP vs. RT outcomes in PI-RADS 5 are lacking, the stronger survival signals in RP for overall high-risk disease favour RP as the initial therapeutic choice when patient comorbidity and functional status permit. Critical imaging parameters such as lesion size, zonal location, extracapsular extension, and PSA density should be factored into decision-making. For example, larger lesions and PI-RADS 5 status both correlate with worse outcomes; therefore, imaging-derived risk modelling may guide tailored treatment escalation.

Notwithstanding the insights available, several gaps remain. First, there are no randomised controlled trials specifically comparing RP versus RT in populations defined by PI-RADS 5 status; many RT studies do not report or stratify outcomes by PI-RADS score, limiting the precision of comparisons; heterogeneity in RT techniques (dose, fractionation, ADT use) and surgical approaches complicates generalisability; and longer follow-up durations are required to assess meaningful endpoints such as MFS and OS in PI-RADS 5 cohorts.

A major limitation of this analysis is the heterogeneity between the two parent cohorts [19,20] which differ substantially in terms of sample size, baseline stage distribution, PSA levels, and follow-up duration. Because only aggregated Kaplan–Meier curves were available, no patient-level variables could be accessed, preventing the use of propensity score matching, multivariable adjustment, or standardised risk balancing. As a result, the reconstructed survival curves may partially reflect underlying differences in baseline disease severity rather than the treatment effect alone. Although both studies reported outcomes stratified by PI-RADS 5, unmeasured differences in comorbidities, age, and Gleason score may still introduce bias. These limitations highlight that the present results should be interpreted as exploratory and hypothesis-generating rather than definitive evidence of comparative effectiveness.

Despite these limitations, the consistency and magnitude of the observed differences are striking. Radiotherapy, when paired with ADT and guided by accurate mpMRI risk stratification, not only improves disease control in high-risk patients but also achieves it more efficiently and cost-effectively. These insights are becoming increasingly relevant in healthcare systems that strive to align outcomes with costs in line with the principles of value-based care.

5. Conclusions

Our analysis suggests that radiotherapy combined with ADT, when guided by mpMRI-based risk stratification, may represent a cost-efficient treatment option for patients with PI-RADS 5 prostate cancer. These findings should be interpreted as exploratory, as they derive from retrospective, aggregated data and warrant prospective validation before application in clinical practice. Nevertheless, the consistent advantage observed in recurrence-free outcomes and economic performance provides a strong rationale for further investigation of mpMRI-guided treatment selection. As precision imaging and modelling tools continue to advance, integrating radiologic, clinical, and economic evidence will become increasingly important for supporting value-based and personalised decision-making in prostate cancer care. Future prospective studies are required to confirm these observations and to refine the role of mpMRI in optimising treatment pathways for patients with aggressive intraprostatic lesions.