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Benign prostatic hyperplasia (BPH) is a non-neoplastic proliferative disease producing lower urinary tract symptoms related to the enlarged prostate. BPH is pathologically characterized by hyperplastic growth in both epithelial and stromal compartments. Androgen signaling is essential for prostate function and androgen blockade is the second-line medical therapy to relieve symptoms of BPH. Here we examined the prostates of probasin promoter-driven prolactin (Pb-PRL) transgenic mice, a robust model of BPH that spontaneously develops prostate enlargement, to investigate prostate regression in response to surgical castration. Serial ultrasound imaging demonstrated very uniform self-limited growth of Pb-PRL prostate volume that is consistent with the benign, limited cellular proliferation characteristic of BPH and that contrasts with the highly variable, exponential growth of murine prostate cancer models. Castration elicited only a partial reduction in prostate volume, relative to castration-induced regression of the normal prostate gland. The anti-androgen finasteride induced a diminished reduction of Pb-PRL prostate volume versus castration alone. The limited extent of Pb-PRL mouse prostate volume regression correlated with the initial volume of the stromal compartment, suggesting a differential sensitivity to androgen withdrawal of the epithelial and stroma compartments. Indeed, two-dimensional morphometric analyses revealed a distinctly reduced rate of regression for the stromal compartment in Pb-PRL mice. The myofibroblast component of the Pb-PRL prostate stroma appeared normal, but contained more fibroblasts and extracellular collagen deposition. Like normal prostate, the rate of regression of the Pb-PRL prostate was partially dependent on TGFß and TNF signaling, but unlike the normal prostate, the extent of castration-induced regression was not affected by TGFß or TNF blockade. Our studies show that androgen deprivation can effectively reduce the overall volume of hyperplastic prostate, but the stromal compartment is relatively resistant, suggesting additional therapies might be required to offer an effective treatment for the clinical manifestations of BPH.

Objective: There is now an unprecedented amount of evidence to consider when revising prostate cancer guidelines. We believe that there is a value in publishing summaries of national clinical guidelines in English for others to read and comment on. Methods: This is part 1 of a summary of the Swedish prostate cancer guidelines that were published in June 2022. It covers the early detection, diagnostics, staging, patient support and management of the non-metastatic disease. Part 2 covers recurrence after local treatment and management of the metastatic disease. Results: The 2022 Swedish guidelines include several new recommendations: rectal iodine-povidone to reduce post-biopsy infections, external beam radiation with focal boost to the tumour, use of a pre-rectal spacer to reduce rectal side effects after external beam radiotherapy in some expert centres, 6 months’ concomitant and adjuvant rather than neoadjuvant and concomitant hormonal treatment together with radiotherapy for unfavourable intermediate and high-risk disease, and adjuvant abiraterone plus prednisolone together with a GnRH agonist for a subgroup of men with very high-risk disease. The Swedish guidelines differ from the European by having more restrictive recommendations regarding genetic testing and pelvic lymph node dissection, the risk group classification, recommending ultra-hypofractionated (7 fractions) external radiotherapy for intermediate and selected high-risk cancers, by not recommending any hormonal treatment together with radiotherapy for favourable intermediate-risk disease, and by recommending bicalutamide monotherapy instead of a GnRH agonist for some patient groups. Conclusions: The 2022 Swedish prostate cancer guidelines include several new recommendations and some that differ from the European guidelines.

Objective: There is now an unprecedented amount of evidence to consider when revising prostate cancer guidelines. We believe that there is a value in publishing summaries of national clinical guidelines in English for others to read and comment on. Methods: This is part 2 of a summary of the Swedish prostate cancer guidelines that were published in June 2022. This part covers recurrence after local treatment and management of metastatic and castration resistant disease. Part 1 covers early detection, diagnostics, staging, patient support and management of non-metastatic disease. Results: The 2022 Swedish guidelines include several new recommendations. Among these is a recommendation of a period of observation with repeated PSA tests for patients with approximately 10 years’ life expectancy who experience a BCR more than 2–5 years after radical prostatectomy, to allow for estimating the PSA doubling time before deciding whether to give salvage radiotherapy or not. Recent results from the PEACE-1 trial led to the recommendation of triple-treatment with a GnRH agonist, abiraterone plus prednisolone and 6 cycles of docetaxel for patients with high-volume metastatic disease who are fit for chemotherapy. The Swedish guidelines differ from the European ones by having more restrictive recommendations about genetic testing of and high-dose zoledronic acid or denosumab treatment for men with metastatic prostate cancer, and by recommending considering bicalutamide monotherapy for selected patients with low-volume metastatic disease. Conclusions: The 2022 Swedish prostate cancer guidelines include several new recommendations and some that differ from the European guidelines.

Background: The HYPO-RT-PC trial compared conventionally fractionated radiotherapy with ultra-hypofractionated radiotherapy in patients with localised prostate cancer. Ultra-hypofractionation was non-inferior to conventional fractionation regarding 5-year failure-free survival and toxicity. We aimed to assess whether patient-reported quality of life (QOL) differs between conventional fractionation and ultra-hypofractionation up to 6 years after treatment in the HYPO-RT-PC trial. Methods: HYPO-RT-PC is a multicentre, open-label, randomised, controlled, non-inferiority, phase 3 trial done in 12 centres (seven university hospitals and five county hospitals) in Sweden and Denmark. Inclusion criteria were histologically verified intermediate-to-high-risk prostate cancer (defined as T1c–T3a with one or two of the following risk factors: stage T3a; Gleason score ≥7; and prostate-specific antigen 10–20 ng/mL with no evidence of lymph node involvement or distant metastases), age up to 75 years, and WHO performance status 0–2. Participants were randomly assigned (1:1) to conventional fractionation (78·0 Gy in 39 fractions, 5 days per week for 8 weeks) or ultra-hypofractionation (42·7 Gy in seven fractions, 3 days per week for 2·5 weeks) via a minimisation algorithm with stratification by trial centre, T-stage, Gleason score, and prostate-specific antigen. QOL was measured using the validated Prostate Cancer Symptom Scale (PCSS) and European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) at baseline, the end of radiotherapy, months 3, 6, 12, and 24 after radiotherapy, every other year thereafter up to 10 years, and at 15 years. The primary endpoint (failure-free survival) has been reported elsewhere. Here we report QOL, a secondary endpoint analysed in the per-protocol population, up to 6 years after radiotherapy. The HYPO-RT-PC trial is registered with the ISRCTN registry, ISRCTN45905321. Findings: Between July 1, 2005, and Nov 4, 2015, 1200 patients were enrolled and 1180 were randomly assigned (conventional fractionation n=591, ultra-hypofractionation n=589); 1165 patients (conventional fractionation n=582, ultra-hypofractionation n=583) were included in this QOL analysis. 158 (71%) of 223 patients in the conventional fractionation group and 146 (66%) of 220 in the ultra-hypofractionation group completed questionnaires at 6 years. The median follow-up was 48 months (IQR 25–72). In seven of ten bowel symptoms or problems the proportion of patients with clinically relevant deteriorations at the end of radiotherapy was significantly higher in the ultra-hypofractionation group than in the conventional fractionation group (stool frequency [p

Purpose To quantify the relationship between the rectal dose distribution and the prevalence of self-reported rectal bleeding among men treated with salvage radiotherapy (ST) delivered by three-dimensional conformal radiotherapy (3DCRT) for prostate cancer. To use this relationship to estimate the risk of rectal bleeding for a contemporary cohort of patients treated with volumetric modulated arc therapy (VMAT) ST. Methods and patients Rectal bleeding of any grade was reported by 56 (22%) of 255 men in a PROM-survey at a median follow-up of 6.7 years after 3DCRT ST. Treatment plan data were extracted and dose–response relationships for the rectal volumes receiving at least 35 Gy (V35Gy) or 63 Gy (V63Gy) were calculated with logistic regression. These relationships were used to estimate the risk of rectal bleeding for a cohort of 253 patients treated with VMAT ST. Results In the dose–response analysis of patients in the 3DCRT ST cohort, both rectal V35Gy and V63Gy were statistically significant parameters in univariable analysis (p = 0.005 and 0.003, respectively). For the dose–response models using either rectal V35Gy or V63Gy, the average calculated risk of rectal bleeding was 14% among men treated with VMAT ST compared to a reported prevalence of 22% for men treated with 3DCRT ST. Conclusions We identified dose–response relationships between the rectal dose distribution and the risk of self-reported rectal bleeding of any grade in a long-term perspective for men treated with 3DCRT ST. Furthermore, VMAT ST may have the potential to decrease the prevalence of late rectal bleeding.

To estimate the long-term risks of severe late toxicities for radiation therapy (RT) following radical prostatectomy (RP) in an unselected nationwide cohort, as severe side-effects are rare but may occur years later.The study population comprised all men undergoing RP between 1997 and 2016 in the Prostate Cancer database Sweden (PCBaSe) (n = 40 962). By (1:2) matching, two cohorts were created: 2789 men exposed to postoperative RT and 5578 unexposed men with comparable age, comorbidities, and year of surgery. Cumulative incidences and rate ratios were calculated for the following outcomes: symptoms and interventions of the urinary or intestinal tract demanding inpatient care, secondary malignancies, and non-prostate cancer mortality.The largest differences were seen for late toxicities affecting the urinary tract. The 10-year cumulative incidences among those exposed to postoperative RT vs the RP-only group were: 17.8% vs 10.5% for procedures of the urinary tract (difference 7.3%, 95% confidence interval [CI] 4.4 to 10.3; relative risk [RR] 1.74, 95% CI 1.47 to 2.05); 6.0% vs 1.2% for haematuria (difference 4.8%, 95% CI 3.1 to 6.5; RR 6.50, 95% CI 4.31 to 10.10); and 2.4% vs 1.1% for bladder cancer (difference 1.4%, 95% CI 0.4 to 2.3; RR 2.71, 95% CI 1.72 to 4.33). The groups were similar regarding intestinal toxicity, other secondary malignancies, and non-prostate cancer mortality. Adjustments for preoperative tumour risk factors did not importantly affect the rate ratios.Severe late toxicity after postoperative RT following RP predominately affects the bladder and can appear many years after RT.

For effective clinical management of patients being treated with 223Ra, there is a need for radiographic response biomarkers to minimize disease progression and to stratify patients for subsequent treatment options. The objective of this study was to evaluate an automated bone scan index (aBSI) as a quantitative assessment of bone scans for radiographic response in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: In a multicenter retrospective study, bone scans from patients with mCRPC treated with monthly injections of 223Ra were collected from 7 hospitals in Sweden. Patients with available bone scans before treatment with 223Ra and at treatment discontinuation were eligible for the study. The aBSI was generated at baseline and at treatment discontinuation. The Spearman rank correlation was used to correlate aBSI with the baseline covariates: alkaline phosphatase (ALP) and prostate-specific antigen (PSA). The Cox proportional-hazards model and Kaplan-Meier curve were used to evaluate the association of covariates at baseline and their change at treatment discontinuation with overall survival (OS). The concordance index (C-index) was used to evaluate the discriminating strength of covariates in predicting OS. Results: Bone scan images at baseline were available from 156 patients, and 67 patients had both a baseline and a treatment discontinuation bone scan (median, 5 doses; interquartile range, 3-6 doses). Baseline aBSI (median, 4.5; interquartile range, 2.4-6.5) was moderately correlated with ALP (r = 0.60, P < 0.0001) and with PSA (r = 0.38, P = 0.003). Among baseline covariates, aBSI (P = 0.01) and ALP (P = 0.001) were significantly associated with OS, whereas PSA values were not (P = 0.059). After treatment discontinuation, 36% (24/67), 80% (54/67), and 13% (9/67) of patients demonstrated a decline in aBSI, ALP, and PSA, respectively. As a continuous variable, the relative change in aBSI after treatment, compared with baseline, was significantly associated with OS (P < 0.0001), with a C-index of 0.67. Median OS in patients with both aBSI and ALP decline (median, 134 wk) was significantly longer than in patients with ALP decline only (median, 77 wk; P = 0.029). Conclusion: Both aBSI at baseline and its change at treatment discontinuation were significant parameters associated with OS. The study warrants prospective validation of aBSI as a quantitative imaging response biomarker to predict OS in patients with mCRPC treated with 223Ra.

The aim of this study was to analyze the required absorbed doses to detectable metastases (Dreq ) when using radionuclides with prostate specific membrane antigen (PSMA)-targeting radioligands to achieve a high probability for metastatic control. The Monte Carlo based analysis was performed for the clinically-used radionuclides yttrium-90, iodine-131, lutetium-177, and actinium-225, and the newly-proposed low-energy electron emitter terbium-161. It was demonstrated that metastatic formation rate highly influenced the metastatic distribution. Lower values generated few large detectable metastases, as in the case with oligo metastases, while high values generated a distribution of multiple small detectable metastases, as observed in patients with diffused visualized metastases. With equal number of detectable metastases, the total metastatic volume burden was 4–6 times higher in the oligo metastatic scenario compared to the diffusely visualized scenario. The Dreq was around 30% higher for the situations with 20 detectable metastases compared to one detectable metastasis. The Dreq for iodine-131 and yttrium-90 was high (920–3300 Gy). The Dreq for lutetium-177 was between 560 and 780 Gy and considerably lower Dreq were obtained for actinium-225 and terbium-161, with 240–330 Gy and 210–280 Gy, respectively. In conclusion, the simulations demonstrated that terbium-161 has the potential for being a more effective targeted radionuclide therapy for metastases using PSMA ligands.

Simple Summary A tremendous effort and rapid development of the prostate-specific membrane antigen (PSMA)-targeting radio ligands for radionuclide therapy has resulted in encouraging response rates for advanced prostate cancer. Different radionuclides have been utilized or suggested as suitable candidates. In this study, a dynamic model of metastatic progress was developed and utilized to estimate a radiopharmaceutical’s potential of obtaining metastatic control of advanced prostate cancer. The simulations performed demonstrated the advantage of utilizing radionuclides with short-range particle emission, i.e., alpha-emitters and low-energy electrons. The recently-proposed beta-emitting radionuclide terbium-161 demonstrates great potential of being a future candidate towards targeted radionuclide therapy of advanced prostate cancer. This is in line with recent encouraging preclinical results and development of upscaling the product quality. Recently, the first in-human application with a [161Tb]Tb-DOTATOC also demonstrated good SPECT image quality, which can enable dosimetry calculations for new 161Tb-based radiopharmaceuticals. Abstract The aim of this study was to analyze the required absorbed doses to detectable metastases (Dreq) when using radionuclides with prostate specific membrane antigen (PSMA)-targeting radioligands to achieve a high probability for metastatic control. The Monte Carlo based analysis was performed for the clinically-used radionuclides yttrium-90, iodine-131, lutetium-177, and actinium-225, and the newly-proposed low-energy electron emitter terbium-161. It was demonstrated that metastatic formation rate highly influenced the metastatic distribution. Lower values generated few large detectable metastases, as in the case with oligo metastases, while high values generated a distribution of multiple small detectable metastases, as observed in patients with diffused visualized metastases. With equal number of detectable metastases, the total metastatic volume burden was 4–6 times higher in the oligo metastatic scenario compared to the diffusely visualized scenario. The Dreq was around 30% higher for the situations with 20 detectable metastases compared to one detectable metastasis. The Dreq for iodine-131 and yttrium-90 was high (920–3300 Gy). The Dreq for lutetium-177 was between 560 and 780 Gy and considerably lower Dreq were obtained for actinium-225 and terbium-161, with 240–330 Gy and 210–280 Gy, respectively. In conclusion, the simulations demonstrated that terbium-161 has the potential for being a more effective targeted radionuclide therapy for metastases using PSMA ligands.

The extent of late side-effects in prostate cancer patients, after radical prostatectomy (RP = reference group) and salvage radiation therapy (SRT) in a self-reporting perspective (PROM) is still under-reported. We aimed to investigate the rate and severity of side-effects and quality-of-life (QoL) according to PROM.A PROM survey was administered to a cohort of SRT patients matched to a reference group with median follow-up 10 years after surgery. In total, 740 patients were analyzed. To investigate the association between SRT versus reference group regarding side-effects and QoL, a Poisson regression analysis was conducted and presented as relative risk estimates (RR) together with 95% confidence intervals regarding questions related to urinary, rectal, sexual symptoms and QoL.RRs ranged from of 1.7-6.5 on rectal symptoms and 1.2-1.4 for urinary symptoms. In general health, QoL and sexual function all RRs were below 1.1. With increasing age, higher RRs were seen for urinary leakage and lowered sexual function whereas longer time following irradiation showed higher RRs for rectal symptoms and rectal leakage. Limitations of this study include the cross-sectional design and lack of baseline assessment.Adding SRT to RP does not seem to result in other than acceptable side-effects in the majority of men receiving SRT when taking a long follow-up time (median 10 years after surgery) into account. However, a subset of men develop severe side-effects where rectal bleeding dominates.

This study compares two different strategies for maintaining a constant bladder volume during a course of postoperative radiotherapy in prostate cancer. In addition, we studied how changes in bladder filling affect the clinical target volume (CTV) and the coverage hereof.Twenty-nine patients with PSA-relapse after radical prostatectomy were divided into two groups: voiding and drinking 300 ml 1 hour before treatment (Group 1); and maintained a comfortably filled bladder (Group 2). The bladder volumes were calculated based on the planning CT (pCT) and a weekly Cone Beam CT (CBCT) during the treatment period. Furthermore, the variability of bladder extension was analyzed and correlated to the volume of the bladder covered with the 95% of the dose (VThe estimated median bladder volumes were 120 ml (95% CI: (93, 154)) and 123 ml (95% CI: (98, 155)) in groups 1 and 2, respectively. The intra-individual variation in bladder volume, assessed as the standard deviation, was 64 ml (95% CI: (46, 105)) in Group 1 and 61 (95% CI: (45, 94)) ml in Group 2. Increasing the bladder volume extended the bladder cranially while the caudal extension was almost constant. The correlation between bladder volume and VThe intention to maintain a constant volume for the bladder is not fulfilled with either of the protocols in this study, and changes in bladder volumes does not seem to affect the position, or the coverage of the CTV.

Purpose Three aspects of the RayPilot real-time tracking system were investigated: (1) feasibility of the transmitter with respect to implantation and explantation procedures, (2) user and patients’ experiences and (3) quantification of the transmitter positional stability in relation to fiducial markers. Methods and materials Ten prostate cancer patients scheduled for radiotherapy received transmitter implantation in the prostate, concomitantly with fiducial markers. Transmitter and marker positions were assessed in 3D by orthogonal kV-imaging at daily treatment setup in eight patients. Results The transmitter was successfully implanted in all patients. Patients reported mild to moderate discomfort and impact on daily activities due to the implant but overall subjective tolerability was good. One patient had spontaneous explantation of the transmitter after four fractions. One patient had transmitter 3D shifts >9 mm, but also inter-marker shifts >6 mm. The mean inter-marker shift in the remaining patients was 2 mm). In three patients, mean transmitter 3D shifts were Conclusions Implantation and explantation of the transmitter is generally feasible and safe. Patient tolerability is good overall. However, due to interfractional transmitter positional instability in this cohort, use of the system for real-time tracking should be combined with other daily setup techniques.

TPS192 Background: Radiotherapy of the primary tumor in metastatic prostate cancer is life-prolonging in patients with limited disease spread. Several different fractionation schedules have been used, most widely used is a four-week schedule of 2.75-3 Gy in 19-20 fractions. More data is emerging around hypo-fractionated radiotherapy in the curative setting. We hypothesize that a modified version of the Scandinavian Hypo-trial fractionation 6.1Gy per fraction x 6 fractions over a span of 2½ week will be non-inferior in side-effects as a 4-week schedule but more convenient for patients and caregivers. Methods: The Hypo-M1 trial is a randomized, stratified, multi-center, phase 3 clinical trial recruiting 420 patients in 9 Swedish centers. Key eligibility criteria include histological confirmed prostate cancer, indication for radiotherapy of low burden metastatic prostate cancer, defined as a max of 4 skeletal metastases at any site or lymph node metastases outside the pelvis and no other diseases or treatments interfering with radiotherapy or a score > 20 on the International prostate symptom score (IPSS) scale. Patients will be randomized to either 3 Gy x 19 or 6.1Gy x 6. Stratification factors are T1-T3 vs T4 and randomizing centre. Type of staging procedures performed, CT and whole-body bone scan is recommended, PSMA-PET allowed and further treatment beyond ADT is recorded but not stratification variables. Standard treatment may include docetaxel, apalutamide, abiraterone and enzalutamide at the treating physician’s discretion. Toxicity will be measured before, at the end of radiotherapy and at 1, 3, 6, 12 months and at 3 years. Measures used are the CTCAE v 5.0 and RTOG scales and QoL life will be measured at the same time points with the Prostate Cancer Symptom Scale (PCSS), a validated QoL instrument focusing on prostate cancer radiotherapy. The primary endpoint is QoL at 3 months and key secondary is acute toxicity at 3 months, late toxicity and QoL at 12 months, failure free survival and cause specific survival. The sample size is calculated for a continuous outcome non-inferiority trial with a one-sided alpha-value of 2.5 % and a beta-value of 80 %. The non-inferiority limit is set to 7.5 % This will require 175 patients with complete follow up in each treatment arm. Expecting a response rate of 80 % for the PCSS at the main time end point the total number of patients in each arm will be 210. The National Prostate Cancer Registry, covering 98% of all prostate cancer cases in Sweden, will be used as CRF including also a randomization module, making this a truly population based clinical trial. As of October 12, 2021, accrual is set to begin in December. The Hypo-M1 trial is an investigator-led, academic trial sponsored by the Swedish Society of Urological Oncology with study coordination provided by Cancer Center of Umeå University Hospital, Umeå, Sweden. Clinical trial information: NCT04612907.

Summary Background Hypofractionated radiotherapy for prostate cancer has gained increased attention due to its proposed high radiation-fraction sensitivity. Recent reports from studies comparing moderately hypofractionated and conventionally fractionated radiotherapy support the clinical use of moderate hypofractionation. To date, there are no published randomised studies on ultra-hypofractionated radiotherapy. Here, we report the outcomes of the Scandinavian HYPO-RT-PC phase 3 trial with the aim to show non-inferiority of ultra-hypofractionation compared with conventional fractionation. Methods In this open-label, randomised, phase 3 non-inferiority trial done in 12 centres in Sweden and Denmark, we recruited men up to 75 years of age with intermediate-to-high-risk prostate cancer and a WHO performance status between 0 and 2. Patients were randomly assigned to ultra-hypofractionation (42·7 Gy in seven fractions, 3 days per week for 2·5 weeks) or conventional fractionated radiotherapy (78·0 Gy in 39 fractions, 5 days per week for 8 weeks). No androgen deprivation therapy was allowed. The primary endpoint was time to biochemical or clinical failure, analysed in the per-protocol population. The prespecified non-inferiority margin was 4% at 5 years, corresponding to a critical hazard ratio (HR) limit of 1·338. Physician-recorded toxicity was measured according to the Radiation Therapy Oncology Group (RTOG) morbidity scale and patient-reported outcome measurements with the Prostate Cancer Symptom Scale (PCSS) questionnaire. This trial is registered with the ISRCTN registry, number ISRCTN45905321. Findings Between July 1, 2005, and Nov 4, 2015, 1200 patients were randomly assigned to conventional fractionation (n=602) or ultra-hypofractionation (n=598), of whom 1180 (591 conventional fractionation and 589 ultra-hypofractionation) constituted the per-protocol population. 1054 (89%) participants were intermediate risk and 126 (11%) were high risk. Median follow-up time was 5·0 years (IQR 3·1–7·0). The estimated failure-free survival at 5 years was 84% (95% CI 80–87) in both treatment groups, with an adjusted HR of 1·002 (95% CI 0·758–1·325; log-rank p=0·99). There was weak evidence of an increased frequency of acute physician-reported RTOG grade 2 or worse urinary toxicity in the ultra-hypofractionation group at end of radiotherapy (158 [28%] of 569 patients vs 132 [23%] of 578 patients; p=0·057). There were no significant differences in grade 2 or worse urinary or bowel late toxicity between the two treatment groups at any point after radiotherapy, except for an increase in urinary toxicity in the ultra-hypofractionation group compared to the conventional fractionation group at 1-year follow-up (32 [6%] of 528 patients vs 13 [2%] of 529 patients; (p=0·0037). We observed no differences between groups in frequencies at 5 years of RTOG grade 2 or worse urinary toxicity (11 [5%] of 243 patients for the ultra-hypofractionation group vs 12 [5%] of 249 for the conventional fractionation group; p=1·00) and bowel toxicity (three [1%] of 244 patients vs nine [4%] of 249 patients; p=0·14). Patient-reported outcomes revealed significantly higher levels of acute urinary and bowel symptoms in the ultra-hypofractionation group compared with the conventional fractionation group but no significant increases in late symptoms were found, except for increased urinary symptoms at 1-year follow-up, consistent with the physician-evaluated toxicity. Interpretation Ultra-hypofractionated radiotherapy is non-inferior to conventionally fractionated radiotherapy for intermediate-to-high risk prostate cancer regarding failure-free survival. Early side-effects are more pronounced with ultra-hypofractionation compared with conventional fractionation whereas late toxicity is similar in both treatment groups. The results support the use of ultra-hypofractionation for radiotherapy of prostate cancer. Funding The Nordic Cancer Union, the Swedish Cancer Society, and the Swedish Research Council.

For effective clinical management of patients being treated with (223)Ra, there is a need for radiographic response biomarkers to minimize disease progression and to stratify patients for subsequent treatment options. The objective of this study was to evaluate an automated bone scan index (aBSI) as a quantitative assessment of bone scans for radiographic response in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: In a multicenter retrospective study, bone scans from patients with mCRPC treated with monthly injections of (223)Ra were collected from 7 hospitals in Sweden. Patients with available bone scans before treatment with (223)Ra and at treatment discontinuation were eligible for the study. The aBSI was generated at baseline and at treatment discontinuation. The Spearman rank correlation was used to correlate aBSI with the baseline covariates: alkaline phosphatase (ALP) and prostate-specific antigen (PSA). The Cox proportional-hazards model and Kaplan–Meier curve were used to evaluate the association of covariates at baseline and their change at treatment discontinuation with overall survival (OS). The concordance index (C-index) was used to evaluate the discriminating strength of covariates in predicting OS. Results: Bone scan images at baseline were available from 156 patients, and 67 patients had both a baseline and a treatment discontinuation bone scan (median, 5 doses; interquartile range, 3–6 doses). Baseline aBSI (median, 4.5; interquartile range, 2.4–6.5) was moderately correlated with ALP (r = 0.60, P < 0.0001) and with PSA (r = 0.38, P = 0.003). Among baseline covariates, aBSI (P = 0.01) and ALP (P = 0.001) were significantly associated with OS, whereas PSA values were not (P = 0.059). After treatment discontinuation, 36% (24/67), 80% (54/67), and 13% (9/67) of patients demonstrated a decline in aBSI, ALP, and PSA, respectively. As a continuous variable, the relative change in aBSI after treatment, compared with baseline, was significantly associated with OS (P < 0.0001), with a C-index of 0.67. Median OS in patients with both aBSI and ALP decline (median, 134 wk) was significantly longer than in patients with ALP decline only (median, 77 wk; P = 0.029). Conclusion: Both aBSI at baseline and its change at treatment discontinuation were significant parameters associated with OS. The study warrants prospective validation of aBSI as a quantitative imaging response biomarker to predict OS in patients with mCRPC treated with (223)Ra.

Radium-223 dichloride (radium-223) was approved for the treatment of patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases in the United States and Europe in 2013. This followed a reported overall survival benefit for patients treated with radium-223 and best standard of care (BSoC) when compared with placebo and BSoC in the ALpharadin in SYMptomatic Prostate CAncer (ALSYMPCA) trial. At that time, docetaxel was the standard first-line choice for patients with metastatic CRPC (mCRPC). Since then, the treatment landscape has changed dramatically with new hormonal agents (abiraterone and enzalutamide) considered to be the first-line choice for many patients. The optimal patient profile for radium-223 in the modern setting, and its best use either in sequence or in combination with other approved agents are unclear, with few definitive guidelines available. This article reports on the views of a group of urologists and medical oncologists experienced in treating patients with mCRPC with radium-223 in routine clinical practice. The aim is to provide an overview of the current use of radium-223 in the treatment of patients with mCRPC, and to discuss best practices for patient selection and on-treatment monitoring. Where agreement was reached, guidance on the optimal use of radium-223 is provided. The article reports on discussions held by a panel of experts attending a meeting that took place in September 2016 in Oslo, Norway, sponsored by Bayer Healthcare. Dr Paul Hoban of Cancer Communications and Consultancy Ltd, Knutsford, UK provided medical writing assistance, which was funded by Bayer Healthcare. Sí

Ultrahypofractionation for prostate cancer : Outcome from the Scandinavian phase 3 HYPO-RT-PC trial

Extreme Hypofractionation versus Conventionally Fractionated Radiotherapy for Intermediate Risk Prostate Cancer : Early Toxicity Results from the Scandinavian Randomized Phase III Trial "HYPO-RT-PC"