BRACHYTHERAPY - Original Article – Volume 25, Issue 1, pp. 31–39 (January–February 2026)

Patricia Willisch, Elena Villafranca, Susana Roldan Ortega, Silvia Rodriguez Villalba, Alai Goñi, Juan Adrian Camus, Luis Sopeña Sanz, Ana Alonso García, Teresa Muñoz Miguelañez, Saul Lopez-Soliño, Beatriz Vázquez-Barreiro, David Büchser

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Interview with Patricia Willisch and David Büchser, co-authors

What was your motivation for initiating this study?
Management of locally recurrent prostate cancer after primary radiotherapy is a significant clinical challenge. While salvage brachytherapy has increasingly been used as a potentially curative option, the supporting evidence has largely come from small, single-institution series with heterogeneous patient selection, dose prescriptions, and fractionation schedules. As a result, several key questions remain open — including what is the optimal biologically effective dose (BED) and the role of androgen deprivation therapy (ADT), and how best should next-generation imaging (NGI) be incorporated into patient selection and follow-up?

With this in mind, we initiated a large, multicentre, retrospective, national study to better understand oncologic outcomes, prognostic factors, and toxicity in patients who were undergoing salvage whole-gland brachytherapy for locally recurrent disease. We were particularly interested to find out whether earlier diagnosis — facilitated by advanced imaging — would translate into improved outcomes, and whether dose and fractionation meaningfully influenced disease control and safety.

What were the main challenges during the work?

The main challenges were those typically associated with retrospective, multicentre research. Clinical practice was not standardised across institutions: how patients were selected, the imaging approaches that were chosen, the doses prescribed, fractionation schedules used and whether or not ADT was used and in what dosage varied considerably. While this heterogeneity reflected real-world practice and strengthened external validity, it also introduced variability that limited our ability to draw firm causal conclusions.

Another important challenge was the rapid evolution of imaging over the study period. The increasing use of prostate-specific membrane antigen (PSMA) or choline PET, for example, has significantly changed how and when recurrences are detected. This technological shift probably influenced both patient selection and outcomes. In addition, the incomplete availability of some clinical and dosimetric variables in certain centres reduced the statistical power of multivariable analyses.

 

 

What are the most important findings of your study?

This study represents, to our knowledge, one of the largest cohorts reported to date of patients who had been treated with salvage prostate brachytherapy. The oncologic outcomes were encouraging. Five- and ten-year biochemical relapse-free survival rates of 64.9% and 61.7% were found, while clinical relapse-free survival rates reached 72.3% and 68.1%. Overall survival rates at five and ten years were 97.9% and 93.6%, and these data highlight the curative potential of this approach in appropriately selected patients.

Classical prognostic factors remained relevant. A Gleason score >7 and higher baseline prostate-specific antigen (PSA) levels were associated with worse biochemical outcomes. Beyond these traditional factors, post-treatment PSA kinetics emerged as particularly informative. A longer period to PSA nadir (>24 months) and lower nadir values were independently associated with improved biochemical and clinical control. These findings reinforced the prognostic importance of PSA dynamics after salvage therapy.

One of the most clinically relevant observations was the apparent impact of early diagnosis. Patients who were treated at lower PSA levels—particularly below 5ng/ml—demonstrated lower recurrence rates, which finding suggested that earlier intervention may improve disease control. The incorporation of NGI, including PSMA PET, facilitated earlier and more accurate detection of recurrence, potentially challenging the traditional reliance on Phoenix criteria alone.

We did not observe significant differences in oncologic outcomes or severe toxicity levels between high- and low-dose-rate (HDR and LDR) brachytherapy. However, within the HDR subgroup, a BED of >216Gy was associated with improved disease control. This potential benefit must be interpreted carefully, as certain fractionation schedules (such as 3 × 10Gy and 4 × 8Gy) were linked to increased urinary toxicity.

Importantly, overall treatment-related toxicity was low. There were no grade 4 events, and grade ≥3 genitourinary and gastrointestinal toxicities were uncommon. These findings indicated the safety of salvage whole-gland brachytherapy when performed in experienced centres.

What are the implications of this research?

These findings reinforce decisions to use salvage brachytherapy as an effective and safe treatment option for selected patients with locally recurrent prostate cancer after radiotherapy. The study underscores the continued relevance of the use of classic clinicopathologic factors, while also highlighting the additional prognostic value of post-treatment PSA kinetics.

The results also suggest that earlier salvage intervention may improve outcomes. The wider integration of NGI into clinical practice may allow us to identify recurrence at a lower disease burden and reconsider traditional thresholds for intervention.

From a therapeutic perspective, BED optimisation appears critical to balance oncologic control and toxicity. Although higher BED values may enhance disease control, careful consideration of fractionation schedules is required to minimise urinary morbidity.

Prospective randomised studies are needed in order to confirm these findings, standardise dose and fractionation strategies, and to better define the role of ADT. Until such data are available, large real-world multicentre analyses such as this provide valuable evidence that can be used to guide clinical decision-making in this increasingly common and complex scenario.

 

 

Patricia Willisch                                                                     

Head of Radiation Oncology Department

Hospital Meixoeiro

Vigo, Spain

 

 

David Büchser

Department of Radiation Oncology

Hospital Universitario Cruces

Instituto de Investigación Sanitaria Biobizkaia

Barakaldo, Spain