Imaging features of the evolving patterns of metastatic prostate cancer.

The pattern of metastases in prostate cancer (PC) is evolving. Increased use of imaging, newer imaging techniques with higher sensitivity for disease detection and patients receiving multiple lines of novel therapies with increased life expectancy are likely to be contributory. Awareness of metastatic disease patterns improves early diagnosis, accurate staging, and initiation of appropriate therapy, and can inform prognostic information and anticipate potential disease complications. The aim of this review is to document the spectrum of metastases in PC including emerging and unusual patterns, and to highlight the role of novel imaging including prostate-specific membrane antigen (PSMA)-positron-emission tomography (PET) and whole-body magnetic resonance imaging (WB-MRI) to improve diagnostic and response assessment accuracy.

Stereotactic Body Radiotherapy for Oligoprogression in Castration-Resistant Prostate Cancer: Early Toxicity Analysis of the TRAP Trial.

AIMS: To assess toxicity and patient quality of life after stereotactic body radiotherapy (SBRT) to oligoprogressive disease (OPD) in patients with metastatic castrate-resistant prostate cancer (CRPC) on androgen receptor targeted agents (ARTA). MATERIAL AND METHODS: This phase II trial enrolled patients with metastatic CRPC with ≤ 2 oligoprogressive lesions in bone, lymph node, lung, or prostate. All patients were receiving systemic treatment with abiraterone or enzalutamide at the time of oligoprogression. All patients received SBRT to the OPD site(s) and continued the current ARTA. Patients received 30 Gy in 5 fractions (alternate days) to the OPD site. The primary endpoint of the trial is to assess if SBRT to OPD sites results in progression free survival of >6 months. The primary endpoint for this toxicity analysis is the rate of grade 3 or higher adverse events at any timepoint up to 6 months after SBRT. Secondary endpoints included comparing pre- and post-SBRT patient-related outcomes reported using visual analogue scale scores and EQ-5D health questionnaire. RESULTS: Forty enrolled patients had at least 6 months of follow-up at the time of analysis. Grade 3 or higher toxicity from any cause recorded using common terminology criteria for adverse events and radiation therapy oncology group was found in 8/40 (20%) of patients, but only 1/40 (2.5%) was deemed possibly related to SBRT. There was no significant difference in mean EQ5D visual analogue scale score from baseline to each timepoint after SBRT (p = 0.449). CONCLUSION: In this prospective phase II clinical trial for OPD whilst on ARTA in the CRPC setting, we report low grade ≥ 3 toxicity after SBRT. There is no discernible change in patient-reported quality of life due to SBRT treatment. The final results of progression-free survival and toxicity of SBRT treatment will be reported once further follow-up is complete.

GI factors, potential to predict prostate motion during radiotherapy; a scoping review.

Purpose: A scoping literature review was conducted to identify gastrointestinal (GI) factors most likely to influence prostate motion during radiotherapy. We proffer that patient specific measurement of these GI factors could predict motion uncertainty during radiotherapy, facilitating personalised care by optimising treatment technique e.g., daily adaption or via bespoke patient pre-habilitation and preparation. Methods: The scoping review was undertaken as per JBI guidelines. Searches were conducted across four databases: Ovid Medline®, EMBASE, CINAHL and EBSCO discovery. Articles written in English from 2010-present were included. Those pertaining to paediatrics, biological women exclusively, infectious and post-treatment GI morbidity and diet were excluded.Common GI factors impacting men were identified and related symptoms, incidence and measurement tools examined. Prevalence among persons with prostate cancer was explored and suitable assessment tools discussed. Results: A preliminary search identified four prominent GI-factors: mental health, co-morbidity and medication, physical activity, and pelvic floor disorder. The scoping search found 3644 articles; 1646 were removed as duplicates. A further 1249 were excluded after title and abstract screening, 162 remained subsequent to full text review: 42 mental health, 53 co-morbidity and medication, 39 physical activity and 28 pelvic floor disorder.Six GI factors prevalent in the prostate cancer population and estimated most likely to influence prostate motion were identified: depression, anxiety, diabetes, obesity, low physical activity, and pelvic floor disorder. Reliable, quick, and easy to use tools are available to quantify these factors. Conclusion: A comprehensive GI factor assessment package suitable to implement into the radiotherapy clinic has been created. Unveiling these GI factors upfront will guide improved personalisation of radiotherapy.

Prostate cancer image guided radiotherapy: Why the commotion over rectal volume and motion?

Introduction: Distended rectums on pre-radiotherapy scans are historically associated with poorer outcomes in patients treated with two-dimensional IGRT. Subsequently, strict rectal tolerances and preparation regimes were implemented. Contemporary IGRT, daily online registration to the prostate, corrects interfraction motion but intrafraction motion remains. We re-examine the need for rectal management strategies when using contemporary IGRT by quantifying rectal volume and its effect on intrafraction motion. Materials and methods: Pre and during radiotherapy rectal volumes and intrafraction motion were retrospectively calculated for 20 patients treated in 5-fractions and 20 treated in 20-fractions. Small (rectal volume at planning-CT ≤ median), and large (volume > median) subgroups were formed, and rectal volume between timepoints and subgroups compared. Rectal volume and intrafraction motion correlation was examined using Spearman's rho. Intrafraction motion difference between small and large subgroups and between fractions with rectal volume < or ≥ 90 cm3 were assessed. Results: Median rectal volume was 74 cm3, 64 cm3 and 65 cm3 on diagnostic-MRI, planning-CT and treatment imaging respectively (ns). No significant correlation was found between patient's rectal volume at planning-CT and median intrafraction motion, nor treatment rectal volume and intrafraction motion for individual fractions. No significant difference in intrafraction motion between small and large subgroups presented and for fractions where rectal volume breached 90 cm3, motion during that fraction was not significantly greater. Conclusion: Larger rectal volumes before radiotherapy and during treatment did not cause greater intrafraction motion. Findings support the relaxation of strict rectal diameter tolerances and do not support the need for rectal preparation when delivering contemporary IGRT to the prostate.

Patterns of Failure After Stereotactic Body Radiotherapy to Sacral Metastases.

AIMS: Stereotactic body radiotherapy (SBRT) is increasingly used to treat sacral metastases. We analysed our centre's local relapse rates and patterns of failure after sacral SBRT and assessed whether using the consensus contouring recommendation (CCR) may have prevented local relapse. MATERIALS AND METHODS: We conducted a single-centre retrospective review of patients treated with sacral SBRT between February 2012 and December 2021. The cumulative incidence of local relapse, patterns of failure and overall survival were determined. Two investigators reviewed planning computed tomography scans and imaging at relapse to determine if local relapse was potentially preventable with a larger CCR-derived radiotherapy field. RESULTS: In total, 34 patients received sacral SBRT, with doses ranging from 24 to 40 Gy over three to five fractions. The most frequently used schedule was 30 Gy in three fractions. Common primaries treated included prostate (n = 16), breast (n = 6), lung (n = 3) and renal (n = 3) cancers. The median follow-up was 20 months (interquartile range 13-55 months). The cumulative incidence of local relapse (4/34) was 2.9% (95% confidence interval 0.2-13.2), 6.3% (95% confidence interval 1.1-18.5) and 16.8% (95% confidence interval 4.7-35.4) at 6 months, 1 year and 2 years, respectively. The patterns of failure were local-only (1/34), local and distant (3/34) and distant relapse (10/34). The overall survival was 96.7% (95% confidence interval 90.5-100) and 90.6% (95% confidence interval 78.6-100) at 1 and 2 years, respectively. For prostate/breast primaries, the cumulative incidence of local relapse was 4.5% (95% confidence interval 0.3-19.4), 4.5% (95% confidence interval 0.3-19.4) and 12.5% (95% confidence interval 1.7-34.8) at 6 months, 1 and 2 years, respectively. Twenty-nine cases (85.3%) deviated from the CCR. Sacral relapse was potentially preventable if the CCR was used in one patient (2.9% of the whole cohort and 25% of the relapsed cohort). DISCUSSION: We have shown excellent local control rates with sacral SBRT, which was largely planned with a margin expansion approach.

MRI-guided adaptive radiotherapy for prostate cancer: When do we need to account for intra-fraction motion?

A shift of the daily plan can mitigate target position changes that occur between daily MR acquisition and treatment for MR-linac radiotherapy, but increases the session time. We demonstrated that our workflow strategy and decision-making process, to determine whether a subsequent shift is necessary, is appropriate.

Prostate Volume Changes during Extreme and Moderately Hypofractionated Magnetic Resonance Image-guided Radiotherapy.

AIMS: Prostate morphological changes during external beam radiotherapy are poorly understood. Excellent soft-tissue visualisation offered by magnetic resonance image-guided radiotherapy (MRIgRT) provides an opportunity to better understand such changes. The aim of this study was to quantify prostate volume and dimension changes occurring during extreme and moderately hypofractionated schedules. MATERIALS AND METHODS: Forty prostate cancer patients treated on the Unity 1.5 Tesla magnetic resonance linear accelerator (MRL) were retrospectively reviewed. The cohort comprised patients treated with 36.25 Gy in five fractions (n = 20) and 60 Gy in 20 fractions (n = 20). The volume of the delineated prostates on reference planning computed tomography (fused with MRI) and daily T2-weighted 2-min session images acquired on Unity were charted. Forty planning computed tomography and 500 MRL prostate volumes were evaluated. The mean absolute and relative change in prostate volume during radiotherapy was compared using a paired t-test (P value <0.01 considered significant to control for multiple comparisons). The maximum dimension of the delineated prostate was measured in three isocentric planes. RESULTS: Significant prostate volume changes, relative to MRL imaging fraction 1 (MRL#1), were seen at all time points for the five-fraction group. The peak mean relative volume increase was 21% (P < 0.001), occurring at MRL#3 and MRL#4 after 14.5 and 21.75 Gy, respectively. Prostate expansion was greatest in the superior-inferior direction; the peak mean maximal extension was 5.9 mm. The maximal extension in the left-right and anterior-posterior directions measured 1.1 and 2.2 mm, respectively. For the 20-fraction group, prostate volume increased relative to MRL#1, for all treatment time points. The mean relative volume increase was 11% (P < 0.001) at MRL#5 after 12 Gy, it then fluctuated between 8 and 13%. From MRL#5 to MRL#20, the volume increase was significant (P < 0.01) for 12 of 16 time points calculated. The peak mean maximal extension in the superior-inferior direction was 3.1 mm. The maximal extension in the left-right and anterior-posterior directions measured 1.7 and 3.7 mm, respectively. CONCLUSION: Significant prostate volume and dimension changes occur during extreme and moderately hypofractionated radiotherapy. The extent of change was greater during extreme hypofractionation. MRIgRT offers the opportunity to reveal, quantify and correct for this deformation.

UK 2022 Consensus on Normal Tissue Dose-Volume Constraints for Oligometastatic, Primary Lung and Hepatocellular Carcinoma Stereotactic Ablative Radiotherapy.

The use of stereotactic ablative radiotherapy (SABR) in the UK has expanded over the past decade, in part as the result of several UK clinical trials and a recent NHS England Commissioning through Evaluation programme. A UK SABR Consortium consensus for normal tissue constraints for SABR was published in 2017, based on the existing literature at the time. The published literature regarding SABR has increased in volume over the past 5 years and multiple UK centres are currently working to develop new SABR services. A review and update of the previous consensus is therefore appropriate and timely. It is hoped that this document will provide a useful resource to facilitate safe and consistent SABR practice.

Evaluation of a urology specialist therapeutic radiographer implemented radiotherapy pathway for prostate cancer patients.

INTRODUCTION: The role of the Urology Specialist Therapeutic Radiographer (USTR) was introduced to support a busy NHS uro-oncology practice. Key objectives were to improve patient preparedness for and experience of radiotherapy, focussed on prostate cancer. Pre-radiotherapy information seminars were developed, and on-treatment patient review managed by the USTRs. To evaluate the revamped patient pathway and direct further improvements, a patient experience survey was designed. METHODS: An 18-point patient questionnaire was produced. The questionnaire captured patient experience and preparedness; pre, during and at completion of treatment. The patient population comprised men receiving radiotherapy for primary prostate cancer within one UK Trust. RESULTS: Two-hundred and fifty-one responses were received. Seventy-three percent of patients felt completely prepared for radiotherapy, higher in those who attended a seminar (77%) compared to those who did not (61%). Eighty-nine and eighty-six percent of respondents were completely satisfied with verbal and written information received prior to commencing radiotherapy respectively. Seventy-three percent of responders would have found additional resources helpful. With respect to on-treatment clinics; eighty-five percent were seen on time or within 20 minutes, eighty-three percent felt fully involved in decisions regarding their care and ninety-one percent reported complete satisfaction with the knowledge of the health care professional reviewing them. The follow-up process was completely understood by eighty-eight percent and overall patient experience rated excellent by eighty-five percent of responders. CONCLUSION: The revamped pathway implemented by USTRs has achieved high levels of satisfaction at all stages of the prostate patient's radiotherapy. By diversifying the format of information giving, the USTRs hope to further meet the information needs of patients. IMPLICATIONS FOR PRACTICE: Validation of a prostate cancer radiotherapy pathway which employs USTRs and utilises a patient preparation seminar. This model could support the introduction of Specialist Therapeutic Radiographers in other Trusts and treatment sites.

Seven or less Fractions is Not the Standard of Care for Intermediate-Risk Prostate Cancer.

Evidence is accumulating for seven and less fractions in localised prostate cancer, including one large randomised trial. However, there is much more evidence yet to come and changing practice in advance of this may be premature. We review the reasons to persist with moderate hypofractionation for prostate cancer radiotherapy, until the results of further phase III studies are known.

The Dandelion Dilemma Revisited for Oligoprogression: Treat the Whole Lawn or Weed Selectively?

Oligoprogressive disease is a relatively new clinical concept describing progression at only a few sites of metastasis in patients with otherwise controlled widespread disease. In the era of well-tolerated targeted treatments, resistance inevitably occurs and overcoming this is a challenge. Local ablative therapy for oligoprogressive disease may allow the continuation of systemic treatments by overcoming the few sub-clones that have developed resistance. Stereotactic body radiotherapy is now frequently used in treating oligometastatic disease using ablative doses with minimally invasive techniques and acceptable toxicity. We discuss the current retrospective clinical evidence base supporting the use of local ablative therapy for oligoprogression in metastatic patients on targeted treatments within multiple tumour sites. As there is currently a lack of published prospective data available, the best management for these patients remains unclear. We discuss current trials in recruitment and the potential advancements in treating this group of patients with stereotactic radiotherapy.

Fiducial marker based intra-fraction motion assessment on cine-MR for MR-linac treatment of prostate cancer.

We have developed a method to determine intrafraction motion of the prostate through automatic fiducial marker (FM) tracking on 3D cine-magnetic resonance (MR) images with high spatial and temporal resolution. Twenty-nine patients undergoing prostate stereotactic body radiotherapy (SBRT), with four implanted cylindrical gold FMs, had cine-MR imaging sessions after each of five weekly fractions. Each cine-MR examination consisted of 55 sequentially obtained 3D datasets ('dynamics'), acquired over a 11 s period, covering a total of 10 min. FM locations in the first dynamic were manually identified by a clinician, FM centers in subsequent dynamics were automatically determined. Center of mass (COM) translations and rotations were determined by calculating the rigid transformations between the FM template of the first and subsequent dynamics. The algorithm was applied to 7315 dynamics over 133 scans of 29 patients and the obtained results were validated by comparing the COM locations recorded by the clinician at the halfway-dynamic (after 5 min) and end dynamic (after 10 min). The mean COM translations at 10 min were X: 0.0 [Formula: see text] 0.8 mm, Y: 1.0 [Formula: see text] 1.9 mm and Z: 0.9 [Formula: see text] 2.0 mm. The mean rotation results at 10 min were X: 0.1 [Formula: see text] 3.9°, Y: 0.0 [Formula: see text] 1.3° and Z: 0.1 [Formula: see text] 1.2°. The tracking success rate was 97.7% with a mean 3D COM error of 1.1 mm. We have developed a robust, fast and accurate FM tracking algorithm for cine-MR data, which allows for continuous monitoring of prostate motion during MR-guided radiotherapy (MRgRT). These results will be used to validate automatic prostate tracking based on soft-tissue contrast.

National survey of fiducial marker insertion for prostate image guided radiotherapy.

INTRODUCTION: In the United Kingdom fiducial marker IGRT is the second most common verification method employed in radical prostate radiotherapy yet little evidence exists to support centres introducing or developing this practice. We developed a survey to elicit current fiducial marker practices adopted in the UK, to recommend standardisation of practice. METHODS: A 16 question survey was distributed across UK Radiotherapy centres via promotion at the British Uro-Oncology Group Conference, 2016. Included were questions relating to workforce planning, patient preparation, insertion procedure and verification methods. The survey was open from September 2016 to January 2017. RESULTS: Results from 15 centres routinely inserting fiducial markers for prostate IGRT are presented. Eleven professional groups insert fiducial markers across the UK. Fourteen centres insert fiducial markers trans-rectally; one trans-perineally. Centres adopting a trans-rectal approach administer prophylactic ciprofloxacin as a single agent or combined with gentamicin or metronidazole; poor agreement between regimes presented. One centre has introduced targeted antibiotic prophylaxis. Five brands of fiducial markers are utilised nationally. Fourteen centres standardly insert three single fiducial markers, two common configurations emerged. Coupled fiducial markers are routinely implanted by one centre. All centres delay at least one week between fiducial marker insertion and planning CT; seven centres wait two weeks. The most common fiducial verification method is two-dimensional, paired kilo Voltage imaging. CONCLUSION: Variation in fiducial marker practice across the UK is considerable. Standardisation is required to support centres and healthcare professionals developing this service. Seven recommendations, to unify practice, have been proposed based on survey results and literature.

An Investigation of Dosimetric Correlates of Acute Toxicity in Prostate Stereotactic Body Radiotherapy: Dose to Urinary Trigone is Associated with Acute Urinary Toxicity.

AIMS: There are limited data on dosimetric correlates of toxicity in stereotactic body radiotherapy (SBRT) for prostate cancer. We aimed to identify potential relationships between dose and toxicity using conventional dose-volume histograms (DVHs) and dose-surface maps (DSMs). MATERIALS AND METHODS: Urinary bladder trigone and rectum DSMs were produced for a single-institution service evaluation cohort of 50 patients receiving SBRT for localised prostate cancer, together with conventional DVHs for bladder and rectum. Patients had been prospectively recruited to this cohort and treated according to a pre-defined protocol to a dose of 36.25 Gy in five fractions. Radiation Therapy Oncology Group (RTOG) and International Prostate Symptom Score (IPSS) toxicity data were recorded prospectively. Logistic regression was used to identify dosimetric predictors of acute IPSS+10 (rise of 10 points or more above baseline) and grade 2+ RTOG toxicity. RESULTS: On univariate analysis, trigone area receiving 40 Gy and trigone Dmax were associated with IPSS+10 (odds ratio 1.06 [1.02-1.11], P = 0.007 and odds ratio 1.54 [1.06-2.25], P = 0.024, respectively). These two variables were highly correlated. In a multivariate model, including all baseline variables, trigone Dmax remained associated with IPSS+10 (odds ratio 1.91 [1.13-3.22], P = 0.016). These findings were not significant with Holm-Bonferroni correction for multiple testing (corrected P value threshold 0.006). No associations were seen between rectal toxicity and DVH or DSM parameters. CONCLUSIONS: Our study suggests a potential relationship between high doses to the urinary bladder trigone and patient-reported urinary toxicity in prostate SBRT, and is consistent with previous studies in conventionally fractionated radiotherapy, justifying further evaluation in larger cohorts.

UK Consensus on Normal Tissue Dose Constraints for Stereotactic Radiotherapy.

Six UK studies investigating stereotactic ablative radiotherapy (SABR) are currently open. Many of these involve the treatment of oligometastatic disease at different locations in the body. Members of all the trial management groups collaborated to generate a consensus document on appropriate organ at risk dose constraints. Values from existing but older reviews were updated using data from current studies. It is hoped that this unified approach will facilitate standardised implementation of SABR across the UK and will allow meaningful toxicity comparisons between SABR studies and internationally.

Pattern of Progression after Stereotactic Body Radiotherapy for Oligometastatic Prostate Cancer Nodal Recurrences.

AIMS: To report the relapse pattern of stereotactic body radiotherapy (SBRT) for oligorecurrent nodal prostate cancer (PCa). MATERIALS AND METHODS: PCa patients with ≤3 lymph nodes (N1/M1a) at the time of recurrence were treated with SBRT. SBRT was defined as a radiotherapy dose of at least 5 Gy per fraction to a biological effective dose of at least 80 Gy to all metastatic sites. Distant progression-free survival was defined as the time interval between the first day of SBRT and appearance of new metastatic lesions, outside the high-dose region. Relapses after SBRT were recorded and compared with the initially treated site. Secondary end points were local control, time to palliative androgen deprivation therapy and toxicity scored using the Common Terminology Criteria for Adverse Events v4.0. RESULTS: Overall, 89 metastases were treated in 72 patients. The median distant progression-free survival was 21 months (95% confidence interval 16-25 months) with 88% of patients having ≤3 metastases at the time of progression. The median time from first SBRT to the start of palliative androgen deprivation therapy was 44 months (95% confidence interval 17-70 months). Most relapses (68%) occurred in nodal regions. Relapses after pelvic nodal SBRT (n = 36) were located in the pelvis (n = 14), retroperitoneum (n = 1), pelvis and retroperitoneum (n = 8) or in non-nodal regions (n = 13). Relapses after SBRT for extrapelvic nodes (n = 5) were located in the pelvis (n = 1) or the pelvis and retroperitoneum (n = 4). Late grade 1 and 2 toxicity was observed in 17% (n = 12) and 4% of patients (n = 3). CONCLUSION: SBRT for oligometastatic PCa nodal recurrences is safe. Most subsequent relapses are again nodal and oligometastatic.

MRI-guided prostate adaptive radiotherapy - A systematic review.

Dose escalated radiotherapy improves outcomes for men with prostate cancer. A plateau for benefit from dose escalation using EBRT may not have been reached for some patients with higher risk disease. The use of increasingly conformal techniques, such as step and shoot IMRT or more recently VMAT, has allowed treatment intensification to be achieved whilst minimising associated increases in toxicity to surrounding normal structures. To support further safe dose escalation, the uncertainties in the treatment target position will need be minimised using optimal planning and image-guided radiotherapy (IGRT). In particular the increasing usage of profoundly hypo-fractionated stereotactic therapy is predicated on the ability to confidently direct treatment precisely to the intended target for the duration of each treatment. This article reviews published studies on the influences of varies types of motion on daily prostate position and how these may be mitigated to improve IGRT in future. In particular the role that MRI has played in the generation of data is discussed and the potential role of the MR-Linac in next-generation IGRT is discussed.