Image-guided Interstitial Brachytherapy in the Treatment of Primary and Recurrent Vulvovaginal Gynaecological Malignancies.

AIMS: To evaluate the use, outcomes and toxicities of high dose rate brachytherapy (HDRB) to the vulvovaginal region in previously irradiated and radiotherapy-naïve patients for primary or recurrent gynaecological malignancies. MATERIALS AND METHODS: From January 2010 to December 2020, 94 women with a median age of 64 years (range 31-88 years) were treated with interstitial HDRB for vulvovaginal disease. Treatment details, including cumulative radiotherapy doses, were recorded together with reported toxicity, using Common Terminology Criteria for Adverse Events (CTCAE) grading. Dosimetric parameters, including D90, V100 and V150 together with treatment response at 3 months, overall survival, relapse-free survival and long-term toxicity data, were collated from referring centres. RESULTS: The median follow-up was 78 months (range 2-301). Primary sites of disease included vagina (37), endometrium (29), vulva (16), ovary (7) and cervix (5). Eighty-six (91.5%) patients were treated with curative intent, eight (8.5%) were palliative treatments. Fifty patients received HDRB for recurrent disease, 39 patients for primary disease and five as part of adjuvant treatment. The anatomical site of disease treated with HDRB ranged from vagina (76), vulva (14) and peri-urethral sites (four). The 2- and 5-year local relapse-free survival rates were 76% and 72%, respectively; 15 patients experienced local failure only, whereas six patients had local and nodal/distant failure. The median time to local recurrence was 8 months (range 2-88 months). The 2- and 5-year overall survival rates for all patients were 67% and 47%, respectively; the median overall survival was 59 months. Seventy-nine (84%) patients had a complete response measured with imaging at 3 months. Grade 3 toxicity was reported in 14 patients (14.8%). CONCLUSION: This retrospective series suggests the use of interstitial brachytherapy for vulvovaginal gynaecological malignancy to be an effective and safe treatment option. Good local control was achieved with a tolerable toxicity profile; it is a valuable treatment modality.

Functional Magnetic Resonance Imaging in Cervical Cancer Diagnosis and Treatment.

Cervical Cancer is the fourth most common cancer in women worldwide. Treatment with chemoradiotherapy followed by brachytherapy achieves high local control, but recurrence with metastatic disease impacts survival. This highlights the need for predictive and prognostic biomarkers identifying populations at risk of poorer treatment response and survival. Magnetic resonance imaging (MRI) is routinely used in cervical cancer and is a potential source for biomarkers. Functional MRI (fMRI) can characterise tumour beyond anatomical MRI, which is limited to the assessment of morphology. This review summarises fMRI techniques used in cervical cancer and examines the role of fMRI parameters as predictive or prognostic biomarkers. Different techniques characterise different tumour factors, which helps to explain the variation in patient outcomes. These can impact simultaneously on outcomes, making biomarker identification challenging. Most studies are small, focussing on single MRI techniques, which raises the need to investigate combined fMRI approaches for a more holistic characterisation of tumour.

Improving Quality of Life with Brachytherapy for Urological Malignancies.

Brachytherapy for localised prostate, muscle-invasive bladder and penile cancer is well established, providing high tumour dose delivery and minimising normal tissue doses compared with external beam techniques. In prostate cancer, the main impact on quality of life relates to diminished sexual function and irritative or obstructive urinary symptoms, which are seen up to 15 years after treatment. Significant changes in bowel function are rare. Compared with radical prostatectomy or external beam radiotherapy, irritative or obstructive urinary symptoms are more prominent, whereas incontinence is less than after radical prostatectomy and bowel changes are less than after external beam radiotherapy. For muscle-invasive bladder cancer, when compared with radical cystectomy, although no difference is seen for urinary symptoms or fatigue, role and social functioning scores are higher and there is better post-treatment sexual function in both men and women. Compared with surgical treatment for penile cancer, brachytherapy results in better erectile function scores than after glansectomy and partial penectomy and high quality of life scores, with good satisfaction ratings for cosmetic appearance.

A National Referral Service for Paediatric Brachytherapy: An Evolving Practice and Outcomes Over 13 Years.

AIMS: Most children requiring radiotherapy receive external beam treatment and few have tumours suitable for brachytherapy. No paediatric radiotherapy centre will treat enough patients from its own normal catchment population for expertise in brachytherapy to be developed and sustained. Following discussion and agreement in the national paediatric radiotherapy group, a service for paediatric brachytherapy in the UK has been developed. We report the process that has evolved over more than 10 years, with survival and functional outcome results. MATERIALS AND METHODS: Since 2009, potential patients have been referred to the central paediatric oncology multidisciplinary team meeting, where imaging, pathology and treatment options are discussed. Since 2013, the National Soft Tissue Sarcoma Advisory Panel has also reviewed most patients, with the principal aim of advising on the most suitable primary tumour management for complex patients. Clinical assessment and examination under anaesthetic with biopsies may be undertaken to confirm the appropriateness of brachytherapy, either alone or following conservative surgery. Fractionated high dose rate brachytherapy was delivered to a computed tomography planned volume after implantation of catheters under ultrasound imaging guidance. Since 2019, follow-up has been in a dedicated multidisciplinary clinic. RESULTS: From 2009 to 2021 inclusive, 35 patients (16 female, 19 male, aged 8 months to 17 years 6 months) have been treated. Histology was soft-tissue sarcoma in 33 patients and carcinoma in two. The treated site was pelvic in 31 patients and head and neck in four. With a median follow-up of 5 years, the local control and overall survival rates are 100%. Complications have been few, and functional outcome is good. CONCLUSION: Brachytherapy is effective for selected paediatric patients, resulting in excellent tumour control and good functional results. It is feasible to deliver paediatric brachytherapy at a single centre within a national referral service.

Translation of Prognostic and Pharmacodynamic Biomarkers from Trial to Non-trial Patients with Metastatic Castration-resistant Prostate Cancer Treated with Docetaxel.

AIMS: We conducted a pooled analysis of four randomised controlled trials and a non-trial retrospective dataset to study the changes in serum prostate-specific antigen (PSA) concentrations during treatment and its impact on survival in men treated with docetaxel for metastatic castration-resistant prostate cancer. We also compared the outcomes and pre-treatment prognostic factors between trial and non-trial patients. MATERIALS AND METHODS: Data were obtained from four randomised controlled trials and a non-trial cohort from a tertiary cancer centre. The PSA kinetics covariates chosen were absolute value (PSAT), best percentage change (BPCH) and tumour growth rate (K). The association between the covariates collected and overall survival was assessed within a Cox proportional hazards model. How well a covariate captured the difference between trial and non-trial patients was assessed by reporting on models with or without trial status as a covariate. RESULTS: We reviewed individual datasets of 2282 patients. The median overall survival for trial patients was 20.4 (95% confidence interval 19.6-22.2) months and for the non-trial cohort was 12.4 (10.7-14.7) months (P < 0.001). Of the pre-treatment factors, we found that only lactate dehydrogenase fully captured the difference in prognosis between the trial and non-trial cohorts. All PSA kinetic metrics appeared to be prognostic in both the trial and non-trial patients. However, the effect size was reduced in non-trial versus trial patients (interaction P < 0.001). Of the time-dependent covariates, we found that BPCH best captured the difference between trial and non-trial patient prognosis. CONCLUSIONS: The analysis presented here highlights how data from open-source trial databases can be combined with emerging clinical practice databases to assess differences between trial versus non-trial patients for particular treatments. These results highlight the importance of developing prognostic models using both pre-treatment and time-dependent biomarkers of new treatments.

Using Real-world Data to Define a Validated Nomogram for Advanced Bladder Cancer Patients Who Respond to Immunotherapy.

AIMS: Immune checkpoint inhibitors (ICIs) are used in incurable urothelial cancers, both in chemo-naïve and platinum-refractory patients. Efficacy and toxicity data published outside controlled clinical trials are limited. We report overall survival, progression-free survival and toxicities of ICIs in locally advanced (LABC) or metastatic bladder cancer (MBC). We aimed to develop and validate a prognostic model for these patients. MATERIALS AND METHODS: A multicentre real-world individual patient-level data study (n = 272) evaluating ICIs in the first-line platinum-ineligible or platinum-refractory setting for LABC/MBC between March 2017 and February 2020 was undertaken. Cox regression analyses evaluated the association of prognostic factors with overall survival. Data were split to create a training (n = 208) and validation (n = 64) cohort. The backward elimination method with a P-value cut-off of 0.05 was used to develop a reduced prognostic model using the training data set. The concordance index and assessment of observed versus predicted survival probabilities were used to evaluate the final model. RESULTS: The median follow-up was 18.9 (15.8-21.5) months. The median overall survival and progression-free survival in the training cohort were 9.2 (95% confidence interval 7.4-10.5) and 4.5 months (3.5-5.7), respectively. The most common grade 1/2 adverse events recorded were fatigue (47.8%) and infection (19.9%). Five key prognostic factors found in the training set were low haemoglobin, high neutrophil count, choice of immunotherapy favouring pembrolizumab, presence of liver metastasis and steroid use within 30 days of treatment. The concordance index for the training and validation cohorts was 0.66 (standard error = 0.05) and 0.64 (standard error = 0.04), respectively, for the final model. A nomogram was developed to calculate the expected survival probabilities based on risk factors. CONCLUSIONS: Real-world data were used to produce a validated prognostic model for overall survival in LABC/MBC treated with ICIs. This model could assist in patient stratification, interpreting and framing future trials incorporating PD-1/PD-L1 inhibitors in LABC/MBC.

Changes in Magnetic Resonance Imaging Radiomic Features in Response to Androgen Deprivation Therapy in Patients with Intermediate- and High-risk Prostate Cancer.

AIMS: The benefits of neoadjuvant androgen deprivation therapy (nADT) in the management of intermediate- and high-risk prostate cancer patients have been well-established. The aim of this study was to identify radiomic prognostic features derived from routine anatomic magnetic resonance imaging (MRI) sequences that can predict the response of the prostate cancer to nADT. MATERIALS AND METHODS: Patients with intermediate- and high-risk prostate cancer (with one of clinical stage ≥ T2c, Gleason score ≥7 or presenting prostate-specific antigen ≥10) who received 3 months of ADT prior to radical external beam radiotherapy were enrolled into this study. The relative blood volume and the relative blood flow were used as dynamic MRI kinetic parameters to quantify vascular changes as responses to nADT. For all pre- and post-nADT data sets, a combination of T2-weighted and contrast-enhanced T1-weighted anatomic images were used to define regions of interest (ROI) as the dominant malignant nodules (DMNs) and the benign prostate (the entire prostate with the summed DMNs being subtracted). MRI textural radiomic features associated with prostate cancer response in the literature of energy and homogeneity were selected. Pyradiomics was used to extract textural features of the ROIs. A Wilcoxon signed-rank test was carried out to investigate if there were statistically significant differences in values of radiomic features between: (i) benign prostate ROI and DMN pre-nADT; (ii) pre- and post-nADT of benign prostate ROI; (iii) pre- and post-nADT of DMN. Changes in radiomic features and dynamic MRI kinetic parameters were correlated using the Spearman correlation test. RESULTS: Twenty prostate cancer patients were recruited into the study. The median time between the first baseline scan and the first on-treatment scan was 91.5 days (range 82-105). One patient had no discernible tumour visible, leaving 19 patients with evaluable data for the analysis. Baseline homogeneity and energy values differed significantly between benign and malignant tissue (P < 0.01). In response to nADT, homogeneity and energy showed reciprocal changes, significantly increased in benign prostate while decreasing in the DMN. The reduction in tumour homogeneity and energy feature values showed a positive association with the decline in tumour blood flow and tumour blood volume induced by androgen deprivation as derived from dynamic MRI parameters. CONCLUSION: Energy and homogeneity radiomic features derived from MRI of benign and malignant prostate showed significant reciprocal changes in response to nADT. This study confirms the potential of these radiomic features to act as surrogate markers of tumour androgen sensitivity due to their strong association with ADT-induced physiological effects in prostate tumours.

A practical approach to bladder preservation with hypofractionated radiotherapy for localised muscle-invasive bladder cancer.

Bladder preservation with trimodality treatment (TMT) is an alternative strategy to radical cystectomy (RC) for the management of localised muscle invasive bladder cancer (MIBC). TMT comprises of transurethral resection of the bladder tumour (TURBT) followed by radiotherapy with concurrent radiosensitisation. TMT studies have shown neo-adjuvant chemotherapy with cisplatin-based regimens is often given to further improve survival outcomes. A hypofractionated radiotherapy regimen is preferable due to its non-inferiority in local control and late toxicities. Radiosensitisation can comprise concurrent chemotherapy (with gemcitabine, cisplatin or combination fluorouracil and mitomycin), CON (carbogen and nicotinomide) or hyperthermic treatment. Radiotherapy techniques are continuously improving and becoming more personalised. As the bladder is a mobile structure subject to volumetric changes from filling, an adaptive approach can optimise bladder coverage and reduce dose to normal tissue. Adaptive radiotherapy (ART) is an evolving field that aims to overcome this. Improved knowledge of tumour biology and advances in imaging techniques aims to further optimise and personalise treatment.

Adjuvant Therapy for High-risk Endometrial Carcinoma.

About one-fifth of endometrial cancers are 'high risk', which carries a poorer prognosis. Management strategies to optimise their survival have been under investigation for many years. Despite recent advances, their overall survival remains relatively poor. The definition of high risk in endometrial cancers has been based on clinicopathological factors until recently, when molecular profiling has shown greater discrimination. There is, however, poor correlation between traditional clinicopathological factors and their molecular profile. This is the subject of ongoing trials to better individualise adjuvant post-hysterectomy treatment. The management of high-risk tumours is traditionally based on surgery followed by radiotherapy, despite no proven overall survival benefit in early stages. The place of chemotherapy remains under investigation, with recent trials showing benefit in more advanced stages. The Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC) and Gynecologic Oncology Group trials support the use of chemoradiation and chemotherapy for stage III and adverse histological subgroups. In addition, there is now early evidence of correlation between benefit from adjuvant chemotherapy based on molecular alterations in the tumour cells. In this review, we look at the current evidence on management strategies in the evolving era of molecular diagnosis and stratification.

Hypoxia and its Modification in Bladder Cancer: Current and Future Perspectives.

Radiotherapy plays an essential role in the curative treatment of muscle-invasive bladder cancer (MIBC). Hypoxia affects the response to MIBC radiotherapy, limiting radiocurability. Likewise, hypoxia influences MIBC genetic instability and malignant progression being associated with metastatic disease and a worse prognosis. Hypoxia identification in MIBC enables treatment stratification and the promise of improved survival. The most promising methods are histopathological markers such as necrosis; biomarkers of protein expression such as HIF-1α, GLUT-1 and CAIX; microRNAs; and novel mRNA signatures. Although hypoxia modification can take different forms, the gold standard remains carbogen and nicotinamide, which improve local control rates in bladder preservation and absolute overall survival with no significant increase in late toxicity. This is an exciting time for evolving therapies such as bioreductive agents, novel oxygen delivery techniques, immunotherapy and poly (ADP-ribose) polymerase 1 (PARP) inhibitors, all in development and representing upcoming trends in MIBC hypoxia modification. Whatever the future holds for hypoxia-modified radiotherapy, there is no doubt of its importance in MIBC. mRNA signatures provide an ideal platform for the selection of those with hypoxic tumours but are yet to qualified and integrated into the clinic. Future interventional trials will require biomarker stratification to ensure optimal treatment response to improve outcomes for patients with MIBC.

Sacral Insufficiency Fracture Following Pelvic Radiotherapy in Gynaecological Malignancies: Development of a Predictive Model.

AIMS: To investigate the time-to-event and the evolution of sacral insufficiency fractures in gynaecological patients receiving pelvic external beam radiotherapy (EBRT) in relation to dosimetric and imaging parameters across a spectrum of radiotherapy delivery techniques, and to develop a predictive model with a clinical nomogram to identify those at risk of sacral insufficiency fracture. MATERIALS AND METHODS: Patients who received radical or adjuvant pelvic EBRT for gynaecological malignancy between 2014 and 2019 were identified. The data collected were: demographics and clinical details; radiotherapy planning data: dose, fractionation, technique (fixed-field intensity-modulated radiotherapy, adaptive arc, and non-adaptive arc), 60 Gy simultaneous integrated boost. Each plan was examined to determine the sacral dose in 5%/Gy3 increments. Follow-up magnetic resonance scans were reviewed for insufficiency fractures, defined as linear low T1-weighted signal intensity with a high short-T1 inversion recovery (STIR) signal. The site of insufficiency fracture was recreated on the planning computed tomography, the dose to insufficiency fracture contours was recorded and insufficiency fractures were determined as healed with resolution of high STIR signal. Univariable analysis was conducted of the clinical variables. The area under the receiver operator characteristic curve and odds ratio of the risk prediction model with 95% confidence interval are reported with a nomogram for use in clinical practice. RESULTS: 115 patients were identified; the median imaging follow-up was 12 months (2-47). 37.4% developed sacral insufficiency fractures; 93.0% were detected within 12 months of EBRT. At the final radiological follow-up, 83.7% of insufficiency fractures remained active. The radiotherapy delivery technique was not associated with insufficiency fracture after adjusting for patient age (P = 0.115). The location of the 60 Gy simultaneous integrated boost planning target volume did not impact upon the site of insufficiency fracture or the dose received by the insufficiency fracture sites. Age and V40Gy3 are predictors for insufficiency fracture and form the clinical risk model (receiver operator characteristic 0.72). CONCLUSIONS: Age and V40Gy3 predict sacral insufficiency fractures; future work should focus on optimising radiotherapy planning with adoption of a bone-sparing planning approach for those patients at high risk of insufficiency fracture.

Complex Clinical Decision-Making Process of Re-Irradiation.

As patients live longer with their cancer as a result of more effective treatment, recurrences and second malignancies in a previously irradiated field are an increasing challenge. The technical advances that enable high-dose radiation to limited volumes, excluding critical normal tissues, have increased the use of re-irradiation for many tumour sites. Minimising the volume, selecting patients with good performance status, negative metastatic screening and longer disease-free intervals are important principles. Despite this there is a narrow therapeutic window, and careful consideration with open discussion, including the patient, of the probable benefit and the implications of potential toxicities will always be essential. In this overview we evaluate the various radiobiological factors that need to be considered for re-irradiation, tissue recovery and dose tolerances in the setting of re-irradiation and summarise the available literature to guide clinicians in their decision-making for re-irradiation to primary and metastatic site/s of disease.

Clinical and imaging findings in cervical cancer and their impact on FIGO and TNM staging - An analysis from the EMBRACE study.

OBJECTIVE: To investigate differences in local tumour staging between clinical examination and MRI and differences between FIGO 2009, FIGO 2018 and TNM in patients with primary cervical cancer undergoing definitive radio-chemotherapy. METHODS: Patients from the prospective observational multi-centre study "EMBRACE" were considered for analysis. All patients had gynaecological examination and pelvic MRI before treatment. Nodal status was assessed by MRI, CT, PET-CT or lymphadenectomy. For this analysis, patients were restaged according to the FIGO 2009, FIGO 2018 and TNM staging system. The local tumour stage was evaluated for MRI and clinical examination separately. Descriptive statistics were used to compare local tumour stages and different staging systems. RESULTS: Data was available from 1338 patients. For local tumour staging, differences between MRI and clinical examination were found in 364 patients (27.2%). Affected lymph nodes were detected in 52%. The two most frequent stages with FIGO 2009 are IIB (54%) and IIIB (16%), with FIGO 2018 IIIC1 (43%) and IIB (27%) and with TNM T2b N0 M0 (27%) and T2b N1 M0 (23%) in this cohort. CONCLUSIONS: MRI and clinical examination resulted in a different local tumour staging in approximately one quarter of patients. Comprehensive knowledge of the differential value of clinical examination and MRI is necessary to define one final local stage, especially when a decision about treatment options is to be taken. The use of FIGO 2009, FIGO 2018 and TNM staging system leads to differences in stage distributions complicating comparability of treatment results. TNM provides the most differentiated stage allocation.

Clinical Guidance for the Management of Patients with Urothelial Cancers During the COVID-19 Pandemic - Rapid Review.

The current COVID-19 pandemic presents a substantial obstacle to cancer patient care. Data from China as well as risk models suppose that cancer patients, particularly those on active, immunosuppressive therapies are at higher risks of severe infection from the illness. In addition, staff illness and restructuring of services to deal with the crisis will inevitably place treatment capacities under significant strain. These guidelines aim to expand on those provided by NHS England regarding cancer care during the coronavirus pandemic by examining the known literature and provide guidance in managing patients with urothelial and rarer urinary tract cancers. In particular, they address the estimated risk and benefits of standard treatments and consider the alternatives in the current situation. As a result, it is recommended that this guidance will help form a framework for shared decision making with patients. Moreover, they do not advise a one-size-fits-all approach but recommend continual assessment of the situation with discussion within and between centres.

Predicting Response to Radiotherapy in Cancer-Induced Bone Pain: Cytokines as a Potential Biomarker?

AIMS: Radiotherapy (XRT) for cancer-induced bone pain (CIBP) has varying levels of efficacy. A biomarker that predicts likely efficacy could stratify XRT to those most likely to benefit. No biomarker is used in clinical practice, but potential candidate cytokines have been identified. The aim of the present study was to examine the relationship between candidate cytokines and analgesic response after XRT. MATERIALS AND METHODS: An exploratory analysis was undertaken on biobank data from patients who had received single fraction (8 Gy) XRT for CIBP. The biobank data were prospectively collected from multiple centres in the UK as part of a larger clinical trial, which had institutional review board approval and all patients provided written informed consent for the use of their data in future research. Phenotypic data, pain assessments as well as plasma samples were collected at baseline (within the 24 h before the XRT) and at follow-up (4 weeks after XRT). Baseline and follow-up samples were analysed and levels of 16 pre-identified cytokines were compared in patients classified as XRT 'responders' or 'non-responders'. RESULTS: Data from 60 patients were analysed. Insulin-like growth factor binding protein 9 (NOV/CCN3/IGFBP-9) and interleukin-1ß (IL-1ß) were identified as potential predictors of response to XRT. A significant relationship was shown between the response to XRT and the ratio of the median level of NOV/CCN3/IGFBP-9 at baseline:follow-up (P = 0.024). Furthermore, for the patients up to 64 years of age, the median level of NOV/CCN3/IGFBP-9 was significantly different between responders and non-responders (P = 0.047). For IL-1ß, the median level was significantly different between responders and non-responders in patients with breast cancer (P = 0.006). CONCLUSION: Although the present findings do not identify robust biomarkers, this is the first such study to examine the role of cytokines in predicting response to XRT in patients with CIBP, and studies that build on these findings are encouraged.

Practical brachytherapy solutions to an age-old quandary.

Cancer is predominantly a disease of the elderly and as population life expectancy increases, so will the incidence of malignant disease. Elderly patients often have other comorbidities and social complexities, increasing the support required to safely deliver all treatment modalities. Brachytherapy is a relatively simple technique by which radiation therapy can be delivered. It offers dosimetric advantages through a highly conformal dose distribution thereby limiting radiation exposure to normal tissues reducing toxicity. Requiring fewer hospital visits, it also offers practical and logistical advantages to the elderly population and in many cases can be performed without the need for general anaesthesia. In tumour streams where brachytherapy forms part of the curative management, it should not be omitted in elderly patients who are medically fit for treatment. In the palliative setting, brachytherapy often offers an excellent means for achieving either local tumour and/or symptom control and should be actively considered in the therapeutic armamentarium of the oncologist in this context.

Single-Dose Focal Salvage High Dose Rate Brachytherapy for Locally Recurrent Prostate Cancer.

AIMS: To evaluate focal high dose rate (HDR) brachytherapy in locally recurrent prostate cancer. MATERIALS AND METHODS: Patients with biochemical relapse after non-surgical primary treatment for localised prostate cancer were selected after a negative screen for metastatic disease. Template mapping biopsies combined with multiparametric magnetic resonance imaging were used to identify the location of the tumour and the focal clinical target volume. The planning aim dose prescription was 19 Gy. Outcome measures were biochemical relapse-free survival and toxicity using International Prostate Symptom Score and Common Terminology Criteria for Adverse Events (version 4.0) scores. RESULTS: Between March 2013 and December 2018, 50 patients underwent salvage HDR brachytherapy. The median follow-up was 21 months (range 1-53). Biochemical progression-free survival at 2 and 3 years was 63% and 46%, respectively. On multivariate analysis, only prostate-specific antigen nadir ≤0.5 ng/ml post-salvage (P = 0.03, hazard ratio 0.04) was associated with biochemical progression-free survival. Relapse was associated with distant metastases in 11/13 patients in whom this was investigated. Late grade 3 genitourinary toxicities were gross haematuria (three patients), severe lower urinary tract symptoms (two patients), erectile dysfunction (one patient) and urethral stricture requiring surgery (four patients). No acute and late grade 4 or 5 genitourinary and no grade 3 or higher gastrointestinal toxicities were recorded. CONCLUSIONS: Focal salvage HDR monotherapy achieves biochemical control in 46% of patients at 3 years with acceptable toxicity rates in selected patients. Biochemical relapse was related to a post-salvage prostate-specific antigen nadir of ≥0.5 ng/ml. Long-term outcomes are needed to assess the impact on the natural history of prostate cancer in these patients.