The 2024 World Congress of Brachytherapy (BT), which was held in July in Maryland, USA, gathered global leaders and researchers to discuss the latest advances in BT techniques and their impact on patient outcomes. This premier event provided a platform for clinicians, physicists and researchers to share new findings, innovative technologies, and future directions in the field, with a particular focus on improving the quality of patients’ lives and minimising treatment-related side effects.

One of the congress's main theme was prostate cancer, and a variety of sessions were dedicated to the exploration of the evolving landscape of prostate cancer treatment.

During the Proffered Papers I session, an article presented by M. Christianen highlighted significant findings regarding late toxicity in patients with intermediate- to high-risk prostate cancer.

Participants in a study were randomised into two treatment arms: external beam radiotherapy (EBRT) alone in 35 fractions of 2.2Gy; or EBRT combined with BT boost in 20 fractions of 2.2Gy, followed by either high-dose-rate (HDR) BT (one fraction of 13Gy) or pulsed-dose-rate (24 fractions of 1.27Gy with a 2.2-hour interval).

The addition of the BT boost compared with EBRT alone resulted in lower rates of grade ≥ 2 late gastrointestinal (GI) toxicity. In comparison, higher rates of grade ≥ 2 late genitourinary (GU) toxicity were observed. However, these differences did not reach statistical significance.

This study provides valuable insights into the long-term effects of combined treatment modalities for prostate cancer. It therefore contributes to the ongoing discussion regarding the balance between efficacy and toxicity in radiotherapy approaches.

During the Prostate Proffered Papers II session, multiple groups highlighted the impact of prostate cancer treatments on erectile function and quality of life.

- Dr. Youssef from the Memorial Sloan Kettering Cancer Center in New York, USA, presented a retrospective comparison of the treatment of patients with localised prostate cancer who had scores on the international index of erectile function-5 (IIEF-5) of greater than 5, and who were treated with either stereotactic body radiation therapy (SBRT) or low-dose-rate (LDR) BT. Erectile function was assessed at baseline and throughout follow-up. The study concluded that patients treated with LDR BT had higher mean IIEF scores during follow-up than did those treated with SBRT, suggesting that the use of BT led to better erectile function outcomes.

- Dr. Lucas Mendez from the London Health Sciences Centre, in Ontario, Canada, highlighted results from the Priapus trial, which investigated a novel LDR BT technique that was designed to spare structures related to erectile dysfunction. This approach was focused on the achievement of contralateral neurovascular bundle D50% of ≤ 50Gy and penile bulb D10% of ≤ 50Gy. However, after treatment of 15 patients, the study authors found that these dosimetric goals were highly stringent and in many cases unachievable.

- Dr. Noelia Sanmamed shared a multi-institutional Canadian experience that involved assessment of the long-term sexual-health-related quality of life (sHRQoL) of prostate cancer patients who were treated with MRI-guided whole-gland HDR-BT boost. The study, which involved 61 patients who were treated with HDR-BT boost plus EBRT and 12 months of androgen deprivation therapy (ADT), found that 50% of patients reported a minimally important difference in sHRQoL five years after treatment. No significant correlation was identified between baseline or dosimetric parameters and the deterioration in sHRQoL.

- In another Canadian prospective trial, presented by Dr Chopade, a dual strategy that was designed to minimise toxicity while preserving the therapeutic benefits of a BT boost was evaluated. This trial combined the use of a rectal spacer with a focal MRI-guided HDR-BT boost for patients with localised prostate cancer. A total of 73 intermediate-risk patients were treated with a 15 Gy gross tumour volume MRI-HDR-BT boost, followed by SBRT (33-30Gy in five fractions) and ADT. After a median follow-up of 43 months, results showed acute grade 1 GU toxicity in 90.4% of patients and GI toxicity in 30.1%. Late GU toxicity was grade 1 in 39.7% of cases, and late grade 1 GI toxicity occurred in 5.5% of patients, with only one patient experiencing grade 2 late GU toxicity. There were no cases of grade 3 or 4 toxicity, and the five-year BCR -free survival rate was 83.7%; events occurred in seven patients (9.6%).

In the monotherapy session, Dr. Martin King presented findings on the potential role of BT monotherapy for patients with unfavourable intermediate-risk (UIR) prostate cancer.

Dr. King stated that BT monotherapy may be sufficient for a subset of patients with UIR prostate cancer. This approach may be suitable for patients who exhibit a single UIR factor and have organ-confined disease (i.e., no suspicion of radiographic extracapsular extension) based on MRI results. Patients at risk of seminal vesicle invasion or lymph node involvement were excluded from this consideration. As EBRT was omitted, patients could potentially be spared the late urinary and rectal toxicities that are associated with combination therapies, and this would have improved the quality of their lives.

In another talk, Dr. Joelle Helou, Canada, discussed various BT options and their efficacy in achieving optimal outcomes for localised prostate cancer.

Dr. Helou highlighted that both HDR and LDR BT achieved lower nadir prostate-specific antigen (PSA) levels compared with SBRT. Among these, LDR BT was associated with the lowest nadir PSA level and offered the convenience of requiring only one outpatient visit for treatment. While patient-reported outcomes were found to be similar across the three techniques, it was noted that acute GU toxicity was higher for the LDR treatment compared with the other two.

Dr. Helou emphasised that a single fraction of HDR-BT should not be offered, but that two-fraction HDR-BT was a viable alternative. The ongoing PR19 study, a randomised Phase II trial in which are evaluated disease outcomes and both acute and long-term toxicities of HDR and LDR BT as monotherapy for localised prostate cancer, is designed to provide further insights into the optimal BT regimen.

During the Snap Oral Prostate Session, two notable studies highlighted the role of salvage BT for focal recurrences in prostate cancer patients after primary radiotherapy. The first study, presented by Colin Belliveau from the Centre Hospitalier de l'Université de Montréal, Canada, explored a combined approach of tumour-targeted HDR-BT and stereotactic radiotherapy (SRT), especially in patients at greater risk of distant prostate or regional failure. Focal recurrence in prostate cancer after initial radiotherapy is a significant challenge. The approach was intended to deliver a median dose of 130 Gy (equivalent dose in 2 Gy fractions (EQD2) α/β 1.4) to the recurrent prostate tumour, followed by SRT that targeted the whole prostate and involved pelvic lymph nodes. Patients also received ADT for six to 18 months.

In terms of toxicity, five grade 2 GU events were reported, all of which resolved without progression to higher-grade toxicities. With a median follow-up of eight months, the study demonstrated favourable early outcomes, and further expansion of the cohort is planned to evaluate long-term efficacy and safety.

The second study, presented by Richard Hsi from the Fred Hutch Cancer Center in Poulsbo, USA, was a Phase II trial in which LDR focal salvage BT that used iodine-125 seeds was examined for patients with biopsy-confirmed local recurrence after EBRT. The study involved 15 patients who each received a prescription dose of 145 Gy to the recurrent tumour. The median follow-up was 27 months, during which 13 patients remained free of biochemical failure.

The results showed minimal GU and GI toxicity, with no adverse events of grade 3 or higher reported. The focal salvage approach provided excellent biochemical control with a favourable toxicity profile, although longer follow-up is necessary to confirm the durability of these outcomes.

The Top Five Abstracts session highlighted critical advances in prostate cancer treatments, with a particular focus on the use of BT. Two of the most notable presentations were delivered by Dr Juanita Crook from BC Cancer – Kelowna, British Columbia, Canada, and Dr Gregory Merrick from the Schiffler Cancer Center, Wheeling Hospital, West Virginia, USA. Both researchers are leaders in BT, and their studies provide valuable insights into the optimisation of treatment approaches for high-risk prostate cancer patients.

Dr Crook’s study compared the impact of the combination of EBRT with either LDR or HDR-BT on health-related quality of life in men with UIR or unfavourable high-risk prostate cancer. The trial included 195 patients, 108 of whom received HDR and 87 LDR BT as a boost to EBRT.

In terms of urinary function, the study found that patients who received HDR experienced an early decline in quality of life after one month but had recovered to baseline levels by six months. In contrast, LDR patients reached their worst urinary function three months after treatment, with a slower recovery that continued until 18 months had passed. After this period, the quality of both HDR and LDR patients’ lives was similar in terms of urinary symptoms. Regarding bowel function, both groups saw declines, but HDR patients recovered more quickly and returned closer to baseline levels and maintained higher quality of life scores than did LDR patients over the five-year follow-up. LDR patients experienced prolonged bowel symptoms, with scores remaining below the threshold for minimum clinically important difference throughout the study.

The study concluded that although both LDR and HDR-BT were effective when combined with EBRT, HDR was associated with a quicker and more favourable recovery in both urinary and bowel quality of life measures. This suggests that HDR may be the preferred modality when the long-term patient experience is considered, especially in terms of minimising prolonged side effects.

Dr. Merrick presented findings from a long-term analysis of the necessity of supplemental EBRT with Pd-103 BT in high-risk prostate cancer patients. The study was based on data from the 44/20 and 20/0 trials, which involved 630 patients in total. Patients in the 44/20 trial were randomised to receive 44 Gy EBRT with a 90 Gy Pd-103 boost or 20 Gy EBRT with a 115 Gy Pd-103 boost, while the 20/0 trial compared 20 Gy EBRT with 125 Gy Pd-103 BT to BT monotherapy (125 Gy Pd-103).

The median follow-up was 11.8 years, and the results showed that overall biochemical failure was 5.8%, prostate cancer-specific mortality (PCSM) was 1.0%, and overall mortality (OM) was 30.4%. Among the 44/20 patients, biochemical failure and PCSM rates were 8.9% and 2.4%, respectively, while for the 20/0 patients, these rates were significantly lower at 3.6% for biochemical failure and 0% for PCSM. The differences between the groups were partially explained by the higher percentage of Gleason score 8-9 patients in the 44/20 group (15.8% vs. 1.6%).

The study found that neither the addition of EBRT nor its dosage significantly impacted biochemical failure or PCSM rates. Instead, factors such as pre-implant PSA levels, Gleason score, and the percentage of positive biopsies were the most important predictors of patient outcomes. The multivariate analysis showed that higher pre-implant PSA and Gleason scores were significantly associated with both biochemical failure and PCSM rates. For patients with successful biochemical control, the median PSA was less than 0.02 ng/ml, which indicated highly effective disease control.

Dr Merrick’s study concluded that, in well-implanted, high-risk prostate cancer patients, the addition of supplemental EBRT did not improve biochemical control or reduce rates of PCSM. This finding supports the notion that the use of Pd-103 BT alone, when delivered with optimal dosimetry and extracapsular coverage, can provide excellent long-term outcomes, and this finding challenges the idea that EBRT addition is necessary in some high-risk cases.

Alfonso Gomez Iturriaga, MD, PhD

Department of Radiation Oncology

Hospital Universitario Cruces

Biobizkaia Health Research Institute Basque Country University UPV/EHU

Barakaldo, Spain

Noelia Sanmamed, MD

Department of Radiation Oncology

Hospital Universitario Clínico San Carlos

Madrid, Spain

Marta Gimeno, MD, PhD

Department of Oncology

Clínica Universidad de Navarra

Pamplona, Spain;

Department of Solid Tumours and Biomarkers

Centre for Applied Medical Research

Pamplona, Spain