Prostate cancer

Patients' Preferences for Cytoreductive Treatments in Newly Diagnosed Metastatic Prostate Cancer: The IP5-MATTER Study (2024)

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Type of publication:
Journal article

Author(s):
Connor M.J.; Genie M.; Dudderidge T.; Wu H.; Sukumar J.; Beresford M.; Bianchini D.; Goh C.; Horan G.; Innominato P.; Khoo V.; Klimowska-Nassar N.; Madaan S.; Mangar S.; McCracken S.; Ostler P.; Paisey S.; Robinson A.; Rai B.; Sarwar N.; *Srihari N.; Jayaprakash K.T.; Varughese M.; Winkler M.; Ahmed H.U.; Watson V.

Citation:
European Urology Oncology. (no pagination), 2024. Date of Publication: 2024.

Abstract:
Background and objective: Cytoreductive treatments for patients diagnosed with de novo synchronous metastatic hormone-sensitive prostate cancer (mHSPC) confer incremental survival benefits over systemic therapy, but these may lead to added toxicity and morbidity. Our objective was to determine patients' preferences for, and trade-offs between, additional cytoreductive prostate and metastasis-directed interventions. Method(s): A prospective multicentre discrete choice experiment trial was conducted at 30 hospitals in the UK between December 3, 2020 and January 25, 2023 (NCT04590976). The individuals were eligible for inclusion if they were diagnosed with de novo synchronous mHSPC within 4 mo of commencing androgen deprivation therapy and had performance status 0-2. A discrete choice experiment instrument was developed to elicit patients' preferences for cytoreductive prostate radiotherapy, prostatectomy, prostate ablation, and stereotactic ablative body radiotherapy to metastasis. Patients chose their preferred treatment based on seven attributes. An error-component conditional logit model was used to estimate the preferences for and trade-offs between treatment attributes. Key findings and limitations: A total of 352 patients were enrolled, of whom 303 completed the study. The median age was 70 yr (interquartile range [IQR] 64-76) and prostate-specific antigen was 94 ng/ml (IQR 28-370). Metastatic stages were M1a 10.9% (33/303), M1b 79.9% (242/303), and M1c 7.6% (23/303). Patients preferred treatments with longer survival and progression-free periods. Patients were less likely to favour cytoreductive prostatectomy with systemic therapy (Coef. -0.448; [95% confidence interval {CI} -0.60 to -0.29]; p < 0.001), unless combined with metastasis-directed therapy. Cytoreductive prostate radiotherapy or ablation with systemic therapy, number of hospital visits, use of a "day-case" procedure, or addition of stereotactic ablative body radiotherapy did not impact treatment choice. Patients were willing to accept an additional cytoreductive treatment with 10 percentage point increases in the risk of urinary incontinence and fatigue to gain 3.4 mo (95% CI 2.8-4.3) and 2.7 mo (95% CI 2.3-3.1) of overall survival, respectively. Conclusions and clinical implications: Patients are accepting of additional cytoreductive treatments for survival benefit in mHSPC, prioritising preservation of urinary function and avoidance of fatigue. Patient Summary: We performed a large study to ascertain how patients diagnosed with advanced (metastatic) prostate cancer at their first diagnosis made decisions regarding additional available treatments for their prostate and cancer deposits (metastases). Treatments would not provide cure but may reduce cancer burden (cytoreduction), prolong life, and extend time without cancer progression. We reported that most patients were willing to accept additional treatments for survival benefits, in particular treatments that preserved urinary function and reduced fatigue.

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Biomarkers in Prostate Cancer: A Review (2024)

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Type of publication:
Journal article

Author(s):
Ahmadieh, Nizar; Zeidan, Toufic; Chaaya, Celine; *Cain, David; Aoude, Marc; Abouchahla, Anita; Kourie, Hampig Raphael; Nemer, Elie.

Citation:
The Gulf Journal of Oncology. 1(44):81-93, 2024 Jan.

Abstract:
BACKGROUND: Prostate cancer (PC) is the second most common cancer in men worldwide. It's the second leading cause cancer men in death. Prognostic tests based on molecular and biomarker analysis of tumor tissue may improve risk stratification of prostate cancer 2. MATERIALS AND METHODS: After a search on Pubmed for PC biomarkers, 72 papers responded to the objectives and will be included in the review. RESULTS: A plethora of biomarkers are predictive for the prognosis of PC and its response to certain therapies, while others, once thought to be indicative of prognosis in PC, were not. CONCLUSIONS: This study can help in the development of diagnostic and prognostic tests of PC and contribute to the ongoing research into already existing tests.

Systematic Review of Focal and Salvage Cryotherapy for Prostate Cancer (2022)

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Type of publication:Systematic Review

Author(s):Chin YF; *Lynn N

Citation:Cureus, 2022 Jun 28; Vol. 14 (6), pp. e26400

Abstract:Cryotherapy is one of the recognised ablative modalities for both primary and salvage therapy for prostate cancer. It presents an alternative, less invasive treatment for an organ-confined disease, improved preservation of surrounding tissue and a more suitable option for patients who are unfit for radical prostatectomy. Nevertheless, the currently available literature is relatively too scarce to provide definite conclusions regarding the treatment outcomes in cryotherapy. The present study aimed to review current oncological and survival outcomes in cryotherapy for primary and recurrent prostate cancer. Furthermore, this study aimed to establish the complications and functional outcomes of cryotherapy for prostate cancer. A literature search was performed on the PubMed, Cochrane and Google Scholar databases. Current guidelines and recommendations from the European Association of Urology were also reviewed. The search keywords used included 'Cryotherapy, Prostate Cancer', 'Cryoablation, Prostate Cancer' and 'Cryosurgery, Focal Prostate Cancer'. Truncations and Boolean operators were used with the keywords. All relevant studies from after 2015, including abstracts and non-English research assessing oncological and functional outcomes and complications, were included. Twenty-six studies consisting of 11,228 patients were reviewed. Fifteen studies assessed the outcomes of primary cryotherapy, whereas 11 studies reported the outcomes in salvage therapy. The patient's age ranged 55-85 years, and the pre-procedural prostate-specific antigen (PSA) ranged 0.01-49.33 ng/mL. A total of 2031 patients were classified to be at low risk, 2,995 were at moderate risk and 253 were at high risk on the D'Amico prostate cancer risk classification system. Follow-ups ranged from 9.0 to 297.6 months. The disease-specific survival rate was 65.5%-100.0%, overall survival was 61.3%-99.1%, the PSA nadir was 0.01-2.63 ng/mL and the overall biochemical recurrence rate was 15.4%-62.0%. The complications included erectile dysfunction (3.7%-88.0%), urinary retention (2.13%-25.30%) and bladder neck stricture/stenosis (3.0%-16.7%). The functional assessment showed a mixture of improved, unchanged or worsened post-procedural outcomes in primary therapy. This systematic review did not find significant differences in the cancer-specific, overall and biochemical-free survival rate between the primary and salvage cryotherapy cohorts. The most common complications encountered in both cohorts were erectile dysfunction, urinary incontinence, lower urinary tract/bladder neck stricture and infection. More prospective and double-arm studies are critically needed to provide guidance on the careful selection of patient cohorts for cryotherapy, whether for curative or salvage intent.

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Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial (2022)

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Type of publication:
Randomised controlled trial

Author(s):
Parker CC; James ND; Brawley CD; Clarke NW; Ali A; Amos CL; Attard G; Chowdhury S; Cook A; Cross W; Dearnaley DP; Douis H; Gilbert DC; Gilson C; Gillessen S; Hoyle A; Jones RJ; Langley RE; Malik ZI; Mason MD; Matheson D; Millman R; Rauchenberger M; Rush H; Russell JM; Sweeney H; Bahl A; Birtle A; Capaldi L; Din O; Ford D; Gale J; Henry A; Hoskin P; Kagzi M; Lydon A; O'Sullivan JM; Paisey SA; Parikh O; Pudney D; Ramani V; Robson P; *Srihari NN; Tanguay J; Parmar MKB; Sydes MR; STAMPEDE Trial Collaborative Group

Citation:
PLoS Medicine, 2022 Jun 07; Vol. 19 (6), pp. e1003998

Abstract:
Background: STAMPEDE has previously reported that radiotherapy (RT) to the prostate improved overall survival (OS) for patients with newly diagnosed prostate cancer with low metastatic burden, but not those with high-burden disease. In this final analysis, we report long-term findings on the primary outcome measure of OS and on the secondary outcome measures of symptomatic local events, RT toxicity events, and quality of life (QoL).Methods and Findings: Patients were randomised at secondary care sites in the United Kingdom and Switzerland between January 2013 and September 2016, with 1:1 stratified allocation: 1,029 to standard of care (SOC) and 1,032 to SOC+RT. No masking of the treatment allocation was employed. A total of 1,939 had metastatic burden classifiable, with 42% low burden and 58% high burden, balanced by treatment allocation. Intention-to-treat (ITT) analyses used Cox regression and flexible parametric models (FPMs), adjusted for stratification factors age, nodal involvement, the World Health Organization (WHO) performance status, regular aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, and planned docetaxel use. QoL in the first 2 years on trial was assessed using prospectively collected patient responses to QLQ-30 questionnaire. Patients were followed for a median of 61.3 months. Prostate RT improved OS in patients with low, but not high, metastatic burden (respectively: 202 deaths in SOC versus 156 in SOC+RT, hazard ratio (HR) = 0·64, 95% CI 0.52, 0.79, p < 0.001; 375 SOC versus 386 SOC+RT, HR = 1.11, 95% CI 0.96, 1.28, p = 0·164; interaction p < 0.001). No evidence of difference in time to symptomatic local events was found. There was no evidence of difference in Global QoL or QLQ-30 Summary Score. Long-term urinary toxicity of grade 3 or worse was reported for 10 SOC and 10 SOC+RT; long-term bowel toxicity of grade 3 or worse was reported for 15 and 11, respectively.Conclusions: Prostate RT improves OS, without detriment in QoL, in men with low-burden, newly diagnosed, metastatic prostate cancer, indicating that it should be recommended as a SOC.Trial Registration: ClinicalTrials.gov NCT00268476, ISRCTN.com ISRCTN78818544.

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Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5-year follow-up results from the STAMPEDE randomised trial (NCT00268476) (2022)

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Type of publication:Randomised controlled trial

Author(s):James N.D.; Clarke N.W.; Cook A.; Ali A.; Hoyle A.P.; Attard G.; Brawley C.D.; Chowdhury S.; Cross W.R.; Dearnaley D.P.; de Bono J.S.; Montana C.D.; Gilbert D.; Gillessen S.; Gilson C.; Jones R.J.; Langley R.E.; Malik Z.I.; Matheson D.J.; Millman R.; Parker C.C.; Pugh C.; Rush H.; Russell J.M.; Berthold D.R.; Buckner M.L.; Mason M.D.; Ritchie A.W.; Birtle A.J.; Brock S.J.; Das P.; Ford D.; Gale J.; Grant W.; Gray E.K.; Hoskin P.; Khan M.M.; Manetta C.; McPhail N.J.; O'Sullivan J.M.; Parikh O.; Perna C.; Pezaro C.J.; Protheroe A.S.; Robinson A.J.; Rudman S.M.; Sheehan D.J.; *Srihari N.N.; Syndikus I.; Tanguay J.; Thomas C.W.; Vengalil S.; Wagstaff J.; Wylie J.P.; Parmar M.K.; Sydes M.R.

Citation:
International Journal of Cancer. 151(3) (pp 422-434), 2022. Date of Publication: 01 Aug 2022.

Abstract:Abiraterone acetate plus prednisolone (AAP) previously demonstrated improved survival in STAMPEDE, a multi-arm, multi-stage platform trial in men starting long-term hormone therapy for prostate cancer. This long-term analysis in metastatic patients was planned for 3yrs after the first results. Standard-of-care (SOC) was androgen deprivation therapy. The comparison randomized patients 1:1 to SOC-alone with or without daily abiraterone acetate 1000mg+prednisolone 5mg (SOC+AAP), continued until disease progression. The primary outcome measure was overall survival. Metastatic disease risk group was classified retrospectively using baseline CT and bone scans by central radiological review and pathology reports. Analyses used Cox proportional hazards & flexible parametric models, adjusted for baseline stratification factors. 1003 patients were contemporaneously randomized (Nov-2011–Jan-2014): median age 67yr; 94% newly-diagnosed; metastatic disease risk group: 48% high, 44% low, 8% un-assessable; median PSA 97ng/mL. At 6.1yr median follow-up, 329 SOC-alone deaths (118 low-risk, 178 high-risk) and 244 SOC+AAP deaths (75 low-risk, 145 high-risk) were reported. Adjusted HR = 0.60 (95%CI:0.50-0.71; P =0.31×10-9 ) favoured SOC+AAP, with 5-yr survival improved from 41% SOC-alone to 60% SOC+AAP. This was similar in low-risk (HR = 0.55; 95%CI:0.41-0.76) and high-risk (HR = 0.54; 95%CI:0.43-0.69) patients. Median and current maximum time on SOC+AAP was 2.4yr and 8.1yr. Toxicity at 4yr post-randomisation was similar, with 16% patients in each group reporting grade 3 or higher toxicity. A sustained and substantial improvement in overall survival of all metastatic prostate cancer patients was achieved with SOC+abiraterone acetate + prednisolone, irrespective of metastatic disease risk group.

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Observation versus screening spinal MRI and pre-emptive treatment for spinal cord compression in patients with castration resistant prostate cancer and spinal metastases in the UK (PROMPTS): an open-label, randomised, controlled, phase 3 trial (2022)

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Type of publication:Randomised controlled trial

Author(s):Dearnaley, David; Hinder, Victoria; Hijab, Adham; Horan, Gail; *Srihari, Narayanan; Rich, Philip; Houston, J Graeme; Henry, Ann M; Gibbs, Stephanie; Venkitaraman, Ram; Cruickshank, Clare; Hassan, Shama; Miners, Alec; Mason, Malcolm; Pedley, Ian; Payne, Heather; Brock, Susannah; Wade, Robert; Robinson, Angus; Din, Omar; Lees, Kathryn; Graham, John; Worlding, Jane; Murray, Julia; Parker, Chris; Griffin, Clare; Sohaib, Aslam; Hall, Emma; PROMPTS investigators

Citation:
The Lancet Oncology. 23(4) (pp 501-513), 2022. Date of Publication: April 2022.

Abstract:BACKGROUND Early diagnosis of malignant spinal cord compression (SCC) is crucial because pretreatment neurological status is the major determinant of outcome. In metastatic castration-resistant prostate cancer, SCC is a clinically significant cause of disease-related morbidity and mortality. We investigated whether screening for SCC with spinal MRI, and pre-emptive treatment if radiological SCC (rSCC) was detected, reduced the incidence of clinical SCC (cSCC) in asymptomatic patients with metastatic castration-resistant prostate cancer and spinal metastasis. METHODS We did a parallel-group, open-label, randomised, controlled, phase 3, superiority trial. Patients with metastatic castration-resistant prostate cancer were recruited from 45 National Health Service hospitals in the UK. Eligible patients were aged at least 18 years, with an Eastern Co-operative Oncology Group performance status of 0-2, asymptomatic spinal metastasis, no previous SCC, and no spinal MRI in the past 12 months. Participants were randomly assigned (1:1), using a minimisation algorithm with a random element (balancing factors were treatment centre, alkaline phosphatase [normal vs raised, with the upper limit of normal being defined at each participating laboratory], number of previous systemic treatments [first-line vs second-line or later], previous spinal treatment, and imaging of thorax and abdomen), to no MRI (control group) or screening spinal MRI (intervention group). Serious adverse events were monitored in the 24 h after screening MRI in the intervention group. Participants with screen-detected rSCC were offered pre-emptive treatment (radiotherapy or surgical decompression was recommended per treating physician's recommendation) and 6-monthly spinal MRI. All patients were followed up every 3 months, and then at month 30 and 36. The primary endpoint was time to and incidence of confirmed cSCC in the intention-to-treat population (defined as all patients randomly assigned), with the primary timepoint of interest being 1 year after randomisation. The study is registered with ISRCTN, ISRCTN74112318, and is now complete. FINDINGS Between Feb 26, 2013, and April 25, 2017, 420 patients were randomly assigned to the control (n=210) or screening MRI (n=210) groups. Median age was 74 years (IQR 68 to 79), 222 (53%) of 420 patients had normal alkaline phosphatase, and median prostate-specific antigen concentration was 48 ng/mL (IQR 17 to 162). Screening MRI detected rSCC in 61 (31%) of 200 patients with assessable scans in the intervention group. As of data cutoff (April 23, 2020), at a median follow-up of 22 months (IQR 13 to 31), time to cSCC was not significantly improved with screening (hazard ratio 0·64 [95% CI 0·37 to 1·11]; Gray's test p=0·12). 1-year cSCC rates were 6·7% (95% CI 3·8-10·6; 14 of 210 patients) for the control group and 4·3% (2·1-7·7; nine of 210 patients) for the intervention group (difference -2·4% [95% CI -4·2 to 0·1]). Median time to cSCC was not reached in either group. No serious adverse events were reported within 24 h of screening. INTERPRETATION Despite the substantial incidence of rSCC detected in the intervention group, the rate of cSCC in both groups was low at a median of 22 months of follow-up. Routine use of screening MRI and pre-emptive treatment to prevent cSCC is not warranted in patients with asymptomatic castration-resistant prostate cancer with spinal metastasis. FUNDING Cancer Research UK.

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Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol (2022)

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Type of publication:
Systematic Review

Author(s):
Attard, Gerhardt; Murphy, Laura; Clarke, Noel W; Cross, William; Jones, Robert J; Parker, Christopher C; Gillessen, Silke; Cook, Adrian; Brawley, Chris; Amos, Claire L; Atako, Nafisah; Pugh, Cheryl; Buckner, Michelle; Chowdhury, Simon; Malik, Zafar; Russell, J Martin; Gilson, Clare; Rush, Hannah; Bowen, Jo; Lydon, Anna; Pedley, Ian; O'Sullivan, Joe M; Birtle, Alison; Gale, Joanna; *Srihari, Narayanan; Thomas, Carys; Tanguay, Jacob; Wagstaff, John; Das, Prantik; Gray, Emma; Alzoueb, Mymoona; Parikh, Omi; Robinson, Angus; Syndikus, Isabel; Wylie, James; Zarkar, Anjali; Thalmann, George; de Bono, Johann S; Dearnaley, David P; Mason, Malcolm D; Gilbert, Duncan; Langley, Ruth E; Millman, Robin; Matheson, David; Sydes, Matthew R; Brown, Louise C; Parmar, Mahesh K B; James, Nicholas D; Systemic Therapy in Advancing or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators

Citation:
Lancet; Dec 2021 [epub ahead of print]

Abstract:
BACKGROUND Men with high-risk non-metastatic prostate cancer are treated with androgen-deprivation therapy (ADT) for 3 years, often combined with radiotherapy. We analysed new data from two randomised controlled phase 3 trials done in a multiarm, multistage platform protocol to assess the efficacy of adding abiraterone and prednisolone alone or with enzalutamide to ADT in this patient population. METHODS These open-label, phase 3 trials were done at 113 sites in the UK and Switzerland. Eligible patients (no age restrictions) had high-risk (defined as node positive or, if node negative, having at least two of the following: tumour stage T3 or T4, Gleason sum score of 8-10, and prostate-specific antigen [PSA] concentration ≥40 ng/mL) or relapsing with high-risk features (≤12 months of total ADT with an interval of ≥12 months without treatment and PSA concentration ≥4 ng/mL with a doubling time of <6 months, or a PSA concentration ≥20 ng/mL, or nodal relapse) non-metastatic prostate cancer, and a WHO performance status of 0-2. Local radiotherapy (as per local guidelines, 74 Gy in 37 fractions to the prostate and seminal vesicles or the equivalent using hypofractionated schedules) was mandated for node negative and encouraged for node positive disease. In both trials, patients were randomly assigned (1:1), by use of a computerised algorithm, to ADT alone (control group), which could include surgery and luteinising-hormone-releasing hormone agonists and antagonists, or with oral abiraterone acetate (1000 mg daily) and oral prednisolone (5 mg daily; combination-therapy group). In the second trial with no overlapping controls, the combination-therapy group also received enzalutamide (160 mg daily orally). ADT was given for 3 years and combination therapy for 2 years, except if local radiotherapy was omitted when treatment could be delivered until progression. In this primary analysis, we used meta-analysis methods to pool events from both trials. The primary endpoint of this meta-analysis was metastasis-free survival. Secondary endpoints were overall survival, prostate cancer-specific survival, biochemical failure-free survival, progression-free survival, and toxicity and adverse events. For 90% power and a one-sided type 1 error rate set to 1·25% to detect a target hazard ratio for improvement in metastasis-free survival of 0·75, approximately 315 metastasis-free survival events in the control groups was required. Efficacy was assessed in the intention-to-treat population and safety according to the treatment started within randomised allocation. STAMPEDE is registered with ClinicalTrials.gov, NCT00268476, and with the ISRCTN registry, ISRCTN78818544. FINDINGS Between Nov 15, 2011, and March 31, 2016, 1974 patients were randomly assigned to treatment. The first trial allocated 455 to the control group and 459 to combination therapy, and the second trial, which included enzalutamide, allocated 533 to the control group and 527 to combination therapy. Median age across all groups was 68 years (IQR 63-73) and median PSA 34 ng/ml (14·7-47); 774 (39%) of 1974 patients were node positive, and 1684 (85%) were planned to receive radiotherapy. With median follow-up of 72 months (60-84), there were 180 metastasis-free survival events in the combination-therapy groups and 306 in the control groups. Metastasis-free survival was significantly longer in the combination-therapy groups (median not reached, IQR not evaluable [NE]-NE) than in the control groups (not reached, 97-NE; hazard ratio [HR] 0·53, 95% CI 0·44-0·64, p<0·0001). 6-year metastasis-free survival was 82% (95% CI 79-85) in the combination-therapy group and 69% (66-72) in the control group. There was no evidence of a difference in metatasis-free survival when enzalutamide and abiraterone acetate were administered concurrently compared with abiraterone acetate alone (interaction HR 1·02, 0·70-1·50, p=0·91) and no evidence of between-trial heterogeneity (I2 p=0·90). Overall survival (median not reached [IQR NE-NE] in the combination-therapy groups vs not reached [103-NE] in the control groups; HR 0·60, 95% CI 0·48-0·73, p<0·0001), prostate cancer-specific survival (not reached [NE-NE] vs not reached [NE-NE]; 0·49, 0·37-0·65, p<0·0001), biochemical failure-free-survival (not reached [NE-NE] vs 86 months [83-NE]; 0·39, 0·33-0·47, p<0·0001), and progression-free-survival (not reached [NE-NE] vs not reached [103-NE]; 0·44, 0·36-0·54, p<0·0001) were also significantly longer in the combination-therapy groups than in the control groups. Adverse events grade 3 or higher during the first 24 months were, respectively, reported in 169 (37%) of 451 patients and 130 (29%) of 455 patients in the combination-therapy and control groups of the abiraterone trial, respectively, and 298 (58%) of 513 patients and 172 (32%) of 533 patients of the combination-therapy and control groups of the abiraterone and enzalutamide trial, respectively. The two most common events more frequent in the combination-therapy groups were hypertension (abiraterone trial: 23 (5%) in the combination-therapy group and six (1%) in control group; abiraterone and enzalutamide trial: 73 (14%) and eight (2%), respectively) and alanine transaminitis (abiraterone trial: 25 (6%) in the combination-therapy group and one (<1%) in control group; abiraterone and enzalutamide trial: 69 (13%) and four (1%), respectively). Seven grade 5 adverse events were reported: none in the control groups, three in the abiraterone acetate and prednisolone group (one event each of rectal adenocarcinoma, pulmonary haemorrhage, and a respiratory disorder), and four in the abiraterone acetate and prednisolone with enzalutamide group (two events each of septic shock and sudden death). INTERPRETATION Among men with high-risk non-metastatic prostate cancer, combination therapy is associated with significantly higher rates of metastasis-free survival compared with ADT alone. Abiraterone acetate with prednisolone should be considered a new standard treatment for this population. FUNDING Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen, and Astellas.

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The largest transcriptomic resource for radiotherapy-treated high-risk prostate cancer: paving the way for companion diagnostic biomarkers (2021)

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Type of publication:Conference abstract

Author(s):Thiruthaneeswaran N.; Bibby B.; Pereira R.; More E.; Hoskin P.; Bristow R.; Choudhury A.; West C.; Wylie J.; *Denley H.; Henry A.

Citation:Journal of Medical Imaging and Radiation Oncology; Sep 2021; vol. 65 ; p. 252

Abstract:Purpose: The Cancer Genome Atlas (TCGA) is a valuable resource for developing and validating gene signatures for personalising treatments. TCGA samples came from patients who received heterogeneous treatments-dominated by surgery. Improving the biological precision of radiotherapy is hampered by the lack of well annotated cohorts that reflect patient populations relevant for radiation oncologists. We aimed to generate transcriptomic data from needle core biopsies for a large multicentre cohort of high-risk prostate cancer patients and use the data to validate published gene signatures. Methods and materials: A total of 478 NCCN classified high-risk patients treated from 2008-2016 were identified: 244 patients received intensity modulated radiotherapy (IMRT) to the prostate only (BEDalpha/beta 1.5-3Gy of 120-180 Gy) and 234 patients received IMRT to the prostate and a high dose rate (HDR) brachytherapy boost (BEDalpha/beta 1.5-3Gy 159-265 Gy). Androgen deprivation was given to all patients for 3-36 months. Biochemical failure was defined as prostate-specific antigen (PSA) rise of >=2 ng/ml above nadir post-radiotherapy. The primary clinical end-point was 7-year biochemical relapse-free survival (bRFS). Gene expression data were generated from diagnostic needle core biopsies using Affymetrix Clariom S arrays. Two (28-gene and 32 gene) published hypoxia gene signatures and a tumour radiosensitivity index (RSI) were tested for prognostic significance [1-3]. Result(s): The median follow-up for the entire cohort was 6.3 years. Both the 28 gene (p = 0.021) and 32-gene (p = 0.033) hypoxia signatures were prognostic for 7-year bRFS. Non-prostate hypoxia signatures were not prognostic. The bRFS for radioresistant (RSI-R) vs radiosensitive (RSI-S) was prognostic in the IMRT EBRT only cohort (p = 0.01) and not in the HDR boost cohort (p = 0.8). Conclusion(s): We generated the largest high-risk prostate radiotherapy cohort with full gene expression data and showed its value in validating published gene signatures. The RSI signature should be explored further to select patients with high-risk prostate cancer who should benefit from dose escalation with a HDR brachytherapy boost. This resource will be a valuable asset for future research generating and validating signatures for personalising radiotherapy in men with prostate cancer.

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Evaluating the Trade-offs Men with Localised Prostate Cancer Make Between the Risks and Benefits of Treatments: The COMPARE Study (2020)

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Type of publication:
Journal article

Author(s):
Watson V, McCartan N, Krucien N, Abu V, Ikenwilo D, Emberton M, Ahmed HU

Study involved patients at Shrewsbury and Telford Hospital NHS Trust

Citation:
Journal of Urology. 2020 Aug;204(2):273-280

Abstract:
PURPOSE: COMPARE (COMparing treatment options for ProstAte cancer) aimed to evaluate and quantify the trade-offs patients make between different aspects of active surveillance and definitive therapy.
METHODS: A Discrete Choice Experiment (DCE) tool was used to elicit patients' preferences for different treatment characteristics in 34 urology departments. Patients with localised prostate cancer completed the DCE within one week of being diagnosed and before they made treatment decisions. The DCE was pre-tested (N=5) and piloted (n=106) with patients. Patients chose their preferred treatment profile based on six characteristics: treatment type (active surveillance, focal therapy, radical therapy), return to normal activities, erectile function, urinary function, not needing more cancer treatment and 10-15 year cancer-specific survival. Different tools were designed for low-intermediate (n=468) and high-risk (n=166) patients. An error-components conditional logit model was used to estimate preferences and trade-offs between treatment characteristics.
RESULTS:Low-intermediate risk patients were willing to trade 6.99% absolute decrease in survival to have active surveillance over definitive therapy. They were willing to trade 0.75%, 0.46% and 0.19% absolute decrease in survival for a one-month reduction in time-to-return to normal activities, and 1% absolute improvements in urinary and sexual function, respectively. High-risk patients were willing to trade 3.10%, 1.04% and 0.41% absolute decrease in survival for a one-month reduction in time-to-return to normal activities and 1% absolute improvements in urinary and sexual function, respectively.
CONCLUSIONS: Patients with low-intermediate risk prostate cancer preferred active surveillance to definitive therapy. Patients of all risks were willing to trade-off cancer-specific survival for improved quality-of-life.Registration:clinicaltrials.gov Registration Identifier NCT01177865Funding:Medical Research Council (UK) (grant reference: G1002509)

Patients’ and partners’ views of care and treatment provided for metastatic castrate‐resistant prostate cancer in the UK (2019)

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Type of publication:
Journal article

Author(s):
Catt S, Matthews L, May S, Payne H, Mason M, Jenkins V.

Citation:
European Journal of Cancer Care. 2019 Nov;28(6):e13140.

Note:
14 of the 37 participants were recruited from the Royal Shrewsbury Hospital

Abstract:
OBJECTIVE: Documentations of the experiences of patients with advanced prostate cancer and their partners are sparse. Views of care and treatment received for metastatic castrate-resistant prostate cancer (mCRPC) are presented here.
METHODS: Structured interviews conducted within 14 days of a systemic therapy for mCRPC starting and 3 months later explored the following: treatment decisions, information provision, perceived benefits and harms of treatment, and effects of these on patients' and partners' lives.
RESULTS: Thirty-seven patients and 33 partners recruited from UK cancer centres participated. The majority of patients (46%) reported pain was their worst symptom and many wanted to discuss its management (baseline-50%; 3 months-33%). Patients and partners believed treatment would delay progression (>75%), improve wellbeing (33%), alleviate pain (≈12%) and extend life (15% patients, 36% partners). At 3 months, most men (42%) said fatigue was the worst treatment-related side effect (SE), 27% experienced unexpected SEs and 54% needed help with SEs. Most patients received SE information (85% written; 75% verbally); many additionally searched the Internet (33% patients; 55% partners). Only 54% of patients said nurse support was accessible.
CONCLUSION: Pain and other symptom management are not optimal. Increased specialist nurse provision and earlier palliative care links are needed. Dedicated clinics may be justified.

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