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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. METHODS: 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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Background and objective: Building on previous research demonstrating better prostate cancer (PC) diagnostics via a biomarker-enhanced approach, this study focuses on cost analysis of PC care using the Stockholm3 test. We assessed the economic impact in European health care systems using real-world evidence for diagnostic outcomes and relevant costs. Methods: We evaluated two PC diagnostic strategies: (1) the conventional prostate-specific antigen (PSA) strategy with magnetic resonance imaging (MRI) and (2) PSA testing with a reflex to biomarkers at PSA ≥1.5 ng/ml in guiding decisions to perform MRI. Data from the Swedish National Prostate Cancer Register and Capio St. Göran Hospital provided real-world evidence, supplemented by health economic modeling. A comprehensive cost analysis was conducted using a Markov model for treatment pathways for four PC disease states and overall spending, for which costs from various European health care systems were used. A deterministic sensitivity analysis was performed across different cost and diagnostic scenarios. Key finding and limitations: The average cost for the four disease states was 2 182 for benign disease, 10 023 for low-grade disease, 13 073 for intermediate- to high-grade localized or locally advance disease, and 271 210 for metastatic disease. The overall spending was 358 239 (7.7%) lower per 1000 men tested in the biomarker-enhanced strategy in comparison to the PSA strategy. The primary cost saving was attributed to lower treatment expenses for metastatic disease. Sensitivity analysis affirmed the robustness of the findings across various diagnostic and treatment scenarios. Conclusions and clinical implications: Biomarker-enhanced diagnostic strategies may reduce health care costs for PC management and are likely to improve quality-adjusted life years in a scenario in which metastatic disease is reduced. Patient summary: We explored different ways to detect prostate cancer more cost-effectively. We found that using a specific blood test, called Stockholm3, after a PSA (prostate-specific antigen) test to decide if an MRI scan (magnetic resonance imaging) is necessary could save money, mainly by identifying localized cancer earlier and reducing the need for expensive treatments for advanced cancer.
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BACKGROUND AND OBJECTIVE: Magnetic resonance imaging (MRI) can detect recurrences after focal therapy for prostate cancer but there is no robust guidance regarding its use. Our objective was to produce consensus recommendations on MRI acquisition, interpretation, and reporting after focal therapy. METHODS: A systematic review was performed in July 2022 to develop consensus statements. A two-round consensus exercise was then performed, with a consensus meeting in January 2023, during which 329 statements were scored by 23 panellists from Europe and North America spanning urology, radiology, and pathology with experience across eight focal therapy modalities. Using RAND Corporation/University of California-Los Angeles methodology, the Transatlantic Recommendations for Prostate Gland Evaluation with MRI after Focal Therapy (TARGET) were based on consensus for statements scored with agreement or disagreement. KEY FINDINGS AND LIMITATIONS: In total, 73 studies were included in the review. All 20 studies (100%) reporting suspicious imaging features cited focal contrast enhancement as suspicious for cancer recurrence. Of 31 studies reporting MRI assessment criteria, the Prostate Imaging-Reporting and Data System (PI-RADS) score was the scheme used most often (20 studies; 65%), followed by a 5-point Likert score (six studies; 19%). For the consensus exercise, consensus for statements scored with agreement or disagreement increased from 227 of 295 statements (76.9%) in round one to 270 of 329 statements (82.1%) in round two. Key recommendations include performing routine MRI at 12 mo using a multiparametric protocol compliant with PI-RADS version 2.1 standards. PI-RADS category scores for assessing recurrence within the ablation zone should be avoided. An alternative 5-point scoring system is presented that includes a major dynamic contrast enhancement (DCE) sequence and joint minor diffusion-weighted imaging and T2-weighted sequences. For the DCE sequence, focal nodular strong early enhancement was the most suspicious imaging finding. A structured minimum reporting data set and minimum reporting standards for studies detailing MRI data after focal therapy are presented. CONCLUSIONS AND CLINICAL IMPLICATIONS: The TARGET consensus recommendations may improve MRI acquisition, interpretation, and reporting after focal therapy for prostate cancer and provide minimum standards for study reporting. PATIENT SUMMARY: Magnetic resonance imaging (MRI) scans can detect recurrent of prostate cancer after focal treatments, but there is a lack of guidance on MRI use for this purpose. We report new expert recommendations that may improve practice.
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Imageamento por Ressonância Magnética , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Imageamento por Ressonância Magnética/normas , Próstata/diagnóstico por imagem , Próstata/patologia , Consenso , Internacionalidade , Recidiva Local de Neoplasia/diagnóstico por imagem , Guias de Prática Clínica como AssuntoRESUMO
BACKGROUND: The role of multiparametric magnetic resonance imaging (MRI) for detecting recurrent prostate cancer after radiotherapy is unclear. OBJECTIVE: To evaluate MRI and MRI-targeted biopsies for detecting intraprostatic cancer recurrence and planning for salvage focal ablation. DESIGN, SETTING, AND PARTICIPANTS: FOcal RECurrent Assessment and Salvage Treatment (FORECAST; NCT01883128) was a prospective cohort diagnostic study that recruited 181 patients with suspected radiorecurrence at six UK centres (2014 to 2018); 144 were included here. INTERVENTION: All patients underwent MRI with 5 mm transperineal template mapping biopsies; 84 had additional MRI-targeted biopsies. MRI scans with Likert scores of 3 to 5 were deemed suspicious. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: First, the diagnostic accuracy of MRI was calculated. Second, the pathological characteristics of MRI-detected and MRI-undetected tumours were compared using the Wilcoxon rank sum test and chi-square test for trend. Third, four biopsy strategies involving an MRI-targeted biopsy alone and with systematic biopsies of one to two other quadrants were studied. Fisher's exact test was used to compare MRI-targeted biopsy alone with the best other strategy for the number of patients with missed cancer and the number of patients with cancer harbouring additional tumours in unsampled quadrants. Analyses focused primarily on detecting cancer of any grade or length. Last, eligibility for focal therapy was evaluated for men with localised (≤T3bN0M0) radiorecurrent disease. RESULTS AND LIMITATIONS: Of 144 patients, 111 (77%) had cancer detected on biopsy. MRI sensitivity and specificity at the patient level were 0.95 (95% confidence interval [CI] 0.92 to 0.99) and 0.21 (95% CI 0.07 to 0.35), respectively. At the prostate quadrant level, 258/576 (45%) quadrants had cancer detected on biopsy. Sensitivity and specificity were 0.66 (95% CI 0.59 to 0.73) and 0.54 (95% CI 0.46 to 0.62), respectively. At the quadrant level, compared with MRI-undetected tumours, MRI-detected tumours had longer maximum cancer core length (median difference 3 mm [7 vs 4 mm]; 95% CI 1 to 4 mm, p < 0.001) and a higher grade group (p = 0.002). Of the 84 men who also underwent an MRI-targeted biopsy, 73 (87%) had recurrent cancer diagnosed. Performing an MRI-targeted biopsy alone missed cancer in 5/73 patients (7%; 95% CI 3 to 15%); with additional systematic sampling of the other ipsilateral and contralateral posterior quadrants (strategy 4), 2/73 patients (3%; 95% CI 0 to 10%) would have had cancer missed (difference 4%; 95% CI -3 to 11%, p = 0.4). If an MRI-targeted biopsy alone was performed, 43/73 (59%; 95% CI 47 to 69%) patients with cancer would have harboured undetected additional tumours in unsampled quadrants. This reduced but only to 7/73 patients (10%; 95% CI 4 to 19%) with strategy 4 (difference 49%; 95% CI 36 to 62%, p < 0.0001). Of 73 patients, 43 (59%; 95% CI 47 to 69%) had localised radiorecurrent cancer suitable for a form of focal ablation. CONCLUSIONS: For patients with recurrent prostate cancer after radiotherapy, MRI and MRI-targeted biopsy, with or without perilesional sampling, will diagnose cancer in the majority where present. MRI-undetected cancers, defined as Likert scores of 1 to 2, were found to be smaller and of lower grade. However, if salvage focal ablation is planned, an MRI-targeted biopsy alone is insufficient for prostate mapping; approximately three of five patients with recurrent cancer found on an MRI-targeted biopsy alone harboured further tumours in unsampled quadrants. Systematic sampling of the whole gland should be considered in addition to an MRI-targeted biopsy to capture both MRI-detected and MRI-undetected disease. PATIENT SUMMARY: After radiotherapy, magnetic resonance imaging (MRI) is accurate for detecting recurrent prostate cancer, with missed cancer being smaller and of lower grade. Targeting a biopsy to suspicious areas on MRI results in a diagnosis of cancer in most patients. However, for every five men who have recurrent cancer, this targeted approach would miss cancers elsewhere in the prostate in three of these men. If further focal treatment of the prostate is planned, random biopsies covering the whole prostate in addition to targeted biopsies should be considered so that tumours are not missed.
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Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Humanos , Masculino , Biópsia/métodos , Biópsia Guiada por Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Estudos Prospectivos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapiaRESUMO
AIMS: Focal therapy treats individual areas of tumour in non-metastatic prostate cancer in patients unsuitable for active surveillance. The aim of this work was to evaluate the cost-effectiveness of focal therapy versus prostatectomy and external beam radiotherapy (EBRT). MATERIALS AND METHODS: A Markov cohort health state transition model with four health states (stable disease, local recurrence, metastatic disease and death) was created, evaluating costs and utilities over a 10-year time horizon for patients diagnosed with non-metastatic prostate cancer. National Health Service (NHS) for England perspective was used, based on direct healthcare costs. Clinical transition probabilities were derived from prostate cancer registries in patients undergoing radical prostatectomy, EBRT and focal therapy using cryotherapy (Boston Scientific) or high-intensity focused ultrasound (HIFU) (Sonablate). Propensity score matching was used to ensure that at-risk populations were comparable. Variables included age, prostate-specific antigen (PSA), International Society of Urological Pathology (ISUP) grade group, maximum cancer core length (mm), T-stage and year of treatment. RESULTS: Focal therapy was associated with a lower overall cost and higher quality-adjusted life year (QALY) gains than either prostatectomy or EBRT, dominating both treatment strategies. Positive incremental net monetary benefit (NMB) values confirm focal therapy as cost-effective versus the alternatives at a willingness to pay (WTP) threshold of £30,000/QALY. One-way deterministic sensitivity analyses revealed consistent results. LIMITATIONS: Data used to calculate the transition probabilities were derived from a limited number of hospitals meaning that other potential treatment options were excluded. Limited data were available on later outcomes and none on quality of life data, therefore, literature-based estimates were used. CONCLUSIONS: Cost-effectiveness modelling demonstrates use of focal therapy (cryotherapy or HIFU) is associated with greater QALY gains at a lower overall cost than either radical prostatectomy or EBRT, representing good value for money in the NHS.
Focal therapy can be used for the primary treatment of individual areas of cancer in those patients with prostate cancer whose disease has not spread (localized or non-metastatic prostate cancer) and whose disease is unsuitable for active monitoring. Focal therapy in these patients results in similar control of the cancer to more invasive therapies, such as surgical removal of the prostate and radiotherapy, with the benefit of fewer sexual, urinary and rectal side effects. This work considered whether using focal therapy (either freezing the cancer cells using cryotherapy or using high-intensity focused ultrasound [HIFU] to destroy cancer cells) was good value for money in the National Health Service (NHS) compared with surgery or radiotherapy. An economic model was developed which considered the relative impact of treatment with focal therapies, surgery or radiotherapy within the NHS in England. Previously collected information from people undergoing treatment for their prostate cancer, together with published literature and clinical opinion, was used within the model to predict the treatment pathway, costs incurred and the results of treatment in terms of patient benefits (effectiveness and quality of life). The model showed that focal therapy using either cryotherapy or HIFU was associated with a lower overall cost and higher patient benefit than either surgery or radiotherapy, indicating that focal therapy represents good value for money in the NHS.
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Análise de Custo-Efetividade , Neoplasias da Próstata , Masculino , Humanos , Medicina Estatal , Qualidade de Vida , Análise Custo-Benefício , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , ProstatectomiaRESUMO
OBJECTIVES: To externally validate a published model predicting failure within 2 years after salvage focal ablation in men with localised radiorecurrent prostate cancer using a prospective, UK multicentre dataset. PATIENTS AND METHODS: Patients with biopsy-confirmed ≤T3bN0M0 cancer after previous external beam radiotherapy or brachytherapy were included from the FOcal RECurrent Assessment and Salvage Treatment (FORECAST) trial (NCT01883128; 2014-2018; six centres), and from the high-intensity focussed ultrasound (HIFU) Evaluation and Assessment of Treatment (HEAT) and International Cryotherapy Evaluation (ICE) UK-based registries (2006-2022; nine centres). Eligible patients underwent either salvage focal HIFU or cryotherapy, with the choice based predominantly on anatomical factors. Per the original multivariable Cox regression model, the predicted outcome was a composite failure outcome. Model performance was assessed at 2 years post-salvage with discrimination (concordance index [C-index]), calibration (calibration curve and slope), and decision curve analysis. For the latter, two clinically-reasonable risk threshold ranges of 0.14-0.52 and 0.26-0.36 were considered, corresponding to previously published pooled 2-year recurrence-free survival rates for salvage local treatments. RESULTS: A total of 168 patients were included, of whom 84/168 (50%) experienced the primary outcome in all follow-ups, and 72/168 (43%) within 2 years. The C-index was 0.65 (95% confidence interval 0.58-0.71). On graphical inspection, there was close agreement between predicted and observed failure. The calibration slope was 1.01. In decision curve analysis, there was incremental net benefit vs a 'treat all' strategy at risk thresholds of ≥0.23. The net benefit was therefore higher across the majority of the 0.14-0.52 risk threshold range, and all of the 0.26-0.36 range. CONCLUSION: In external validation using prospective, multicentre data, this model demonstrated modest discrimination but good calibration and clinical utility for predicting failure of salvage focal ablation within 2 years. This model could be reasonably used to improve selection of appropriate treatment candidates for salvage focal ablation, and its use should be considered when discussing salvage options with patients. Further validation in larger, international cohorts with longer follow-up is recommended.
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Neoplasias da Próstata , Terapia de Salvação , Humanos , Masculino , Biópsia , Braquiterapia , Recidiva Local de Neoplasia , Estudos Prospectivos , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/radioterapia , Terapia de Salvação/efeitos adversos , Resultado do Tratamento , Estudos Multicêntricos como Assunto , Ensaios Clínicos como AssuntoRESUMO
PURPOSE: In older patients who do not wish to undergo watchful waiting, focal therapy could be an alternative to the more morbid radical treatment. We evaluated the role of focal therapy in patients 70 years and older as an alternative management modality. MATERIALS AND METHODS: A total of 649 patients across 11 UK sites receiving focal high-intensity focused ultrasound or cryotherapy between June 2006 and July 2020 reported within the UK-based HEAT (HIFU Evaluation and Assessment of Treatment) and ICE (International Cryotherapy Evaluation) registries were evaluated. Primary outcome was failure-free survival, defined by need for more than 1 focal reablation, progression to radical treatment, development of metastases, need for systemic treatment, or prostate cancer-specific death. This was compared to the failure-free survival in patients undergoing radical treatment via a propensity score weighted analysis. RESULTS: Median age was 74 years (IQR: 72, 77) and median follow-up 24 months (IQR: 12, 41). Sixty percent had intermediate-risk disease and 35% high-risk disease. A total of 113 patients (17%) required further treatment. Sixteen had radical treatment and 44 required systemic treatment. Failure-free survival was 82% (95% CI: 76%-87%) at 5 years. Comparing patients who had radical therapy to those who had focal therapy, 5-year failure-free survival was 96% (95% CI: 93%-100%) and 82% (95% CI: 75%-91%) respectively (P < .001). Ninety-three percent of those in the radical treatment arm had received radiotherapy as their primary treatment with its associated use of androgen deprivation therapy, thereby leading to potential overestimation of treatment success in the radical treatment arm, especially given the similar metastases-free and overall survival rates seen. CONCLUSIONS: We propose focal therapy to be an effective management option for the older or comorbid patient who is unsuitable for or not willing to undergo radical treatment.
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Técnicas de Ablação , Neoplasias da Próstata , Idoso , Humanos , Masculino , Antagonistas de Androgênios , Próstata/patologia , Antígeno Prostático Específico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Resultado do TratamentoRESUMO
Approaches and techniques used for diagnostic prostate biopsy have undergone considerable evolution over the past few decades: from the original finger-guided techniques to the latest MRI-directed strategies, from aspiration cytology to tissue core sampling, and from transrectal to transperineal approaches. In particular, increased adoption of transperineal biopsy approaches have led to reduced infectious complications and improved antibiotic stewardship. Furthermore, as image fusion has become integral, these novel techniques could be incorporated into prostate biopsy methods in the future, enabling 3D-ultrasonography fusion reconstruction, molecular targeting based on PET imaging and autonomous robotic-assisted biopsy.
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Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Biópsia Guiada por Imagem , Biópsia , Ultrassonografia , Imageamento por Ressonância Magnética/métodos , Ultrassonografia de Intervenção/métodosRESUMO
BACKGROUND: Recurrent prostate cancer after radiotherapy occurs in one in five patients. The efficacy of prostate magnetic resonance imaging (MRI) in recurrent cancer has not been established. Furthermore, high-quality data on new minimally invasive salvage focal ablative treatments are needed. OBJECTIVE: To evaluate the role of prostate MRI in detection of prostate cancer recurring after radiotherapy and the role of salvage focal ablation in treating recurrent disease. DESIGN, SETTING, AND PARTICIPANTS: The FORECAST trial was both a paired-cohort diagnostic study evaluating prostate multiparametric MRI (mpMRI) and MRI-targeted biopsies in the detection of recurrent cancer and a cohort study evaluating focal ablation at six UK centres. A total of 181 patients were recruited, with 155 included in the MRI analysis and 93 in the focal ablation analysis. INTERVENTION: Patients underwent choline positron emission tomography/computed tomography and a bone scan, followed by prostate mpMRI and MRI-targeted and transperineal template-mapping (TTPM) biopsies. MRI was reported blind to other tests. Those eligible underwent subsequent focal ablation. An amendment in December 2014 permitted focal ablation in patients with metastases. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcomes were the sensitivity of MRI and MRI-targeted biopsies for cancer detection, and urinary incontinence after focal ablation. A key secondary outcome was progression-free survival (PFS). RESULTS AND LIMITATIONS: Staging whole-body imaging revealed localised cancer in 128 patients (71%), with involvement of pelvic nodes only in 13 (7%) and metastases in 38 (21%). The sensitivity of MRI-targeted biopsy was 92% (95% confidence interval [CI] 83-97%). The specificity and positive and negative predictive values were 75% (95% CI 45-92%), 94% (95% CI 86-98%), and 65% (95% CI 38-86%), respectively. Four cancer (6%) were missed by TTPM biopsy and six (8%) were missed by MRI-targeted biopsy. The overall MRI sensitivity for detection of any cancer was 94% (95% CI 88-98%). The specificity and positive and negative predictive values were 18% (95% CI 7-35%), 80% (95% CI 73-87%), and 46% (95% CI 19-75%), respectively. Among 93 patients undergoing focal ablation, urinary incontinence occurred in 15 (16%) and five (5%) had a grade ≥3 adverse event, with no rectal injuries. Median follow-up was 27 mo (interquartile range 18-36); overall PFS was 66% (interquartile range 54-75%) at 24 mo. CONCLUSIONS: Patients should undergo prostate MRI with both systematic and targeted biopsies to optimise cancer detection. Focal ablation for areas of intraprostatic recurrence preserves continence in the majority, with good early cancer control. PATIENT SUMMARY: We investigated the role of magnetic resonance imaging (MRI) scans of the prostate and MRI-targeted biopsies in outcomes after cancer-targeted high-intensity ultrasound or cryotherapy in patients with recurrent cancer after radiotherapy. Our findings show that these patients should undergo prostate MRI with both systematic and targeted biopsies and then ablative treatment focused on areas of recurrent cancer to preserve their quality of life. This trial is registered at ClinicalTrials.gov as NCT01883128.
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Neoplasias da Próstata , Incontinência Urinária , Biópsia , Estudos de Coortes , Humanos , Biópsia Guiada por Imagem , Imageamento por Ressonância Magnética/métodos , Masculino , Recidiva Local de Neoplasia/patologia , Estudos Prospectivos , Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Qualidade de VidaRESUMO
BACKGROUND: Non-muscle-invasive bladder cancer (NMIBC) is one of the most expensive cancers owing to frequent follow-up cystoscopies for detection of recurrence. OBJECTIVE: To assess if the noninvasive ADXBLADDER urine test could permit a less intensive surveillance schedule for patients with low-grade (LG) pTa tumor without carcinoma in situ (CIS) at the previous diagnosis. DESIGN, SETTING, AND PARTICIPANTS: In a prospective, double-blind, multicenter study, 629 patients underwent follow-up cystoscopy, transurethral resection of bladder tumor/biopsy of suspect lesions, and ADXBLADDER testing. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Diagnostic test accuracy and decision curve analysis were used to evaluate the impact of ADXBLADDER on decision-making on whether to perform follow-up cystoscopy. The primary endpoint was the negative predictive value (NPV) of ADXBLADDER for detection of high-grade and/or CIS (HG/CIS) recurrence and its impact on reducing unnecessary cystoscopies. RESULTS AND LIMITATIONS: ADXBLADDER had sensitivity of 66.7% (95% confidence interval [CI] 34.9-90.1%) and an NPV of 99.15% (95% CI 97.8-99.8%) for detection of HG/CIS recurrence. The probability of HG/CIS recurrence was 5.0% for ADXBLADDER-positive patients and 0.85% for ADXBLADDER-negative patients. For HG/CIS recurrence threshold probabilities between 0.85% and 5.0%, ADXBLADDER yields a net benefit with omission of cystoscopy for ADXBLADDER-negative patients. The corresponding net reduction in unnecessary cystoscopies ranges from 11 to 62 per 100 patients. CONCLUSIONS: Patients with LG pTa tumor at the previous diagnosis, for which the risk of HG/CIS recurrence is low and the ADXBLADDER NPV for ruling out HG/CIS recurrence is 99.15%, are ideally suited for a less intensive, personalized follow-up surveillance strategy using ADXBLADDER, with omission of cystoscopy for ADXBLADDER-negative patients. PATIENT SUMMARY: ADXBLADDER is a urine test that can predict the probability of recurrence of bladder cancer. Patients diagnosed with low-grade cancer confined to the bladder mucosa are ideally suited for less intensive follow-up using this test, which could reduce unnecessary cystoscopy procedures for those with a negative result, potentially improve quality of life, and reduce overall health care costs.
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Neoplasias não Músculo Invasivas da Bexiga , Qualidade de Vida , Humanos , Estudos ProspectivosRESUMO
BACKGROUND: Focal therapy aims to treat areas of cancer to confer oncological control whilst reducing treatment-related functional detriment. OBJECTIVE: To report oncological outcomes and adverse events following focal high-intensity focused ultrasound (HIFU) for treating nonmetastatic prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: An analysis of 1379 patients with ≥6 mo of follow-up prospectively recorded in the HIFU Evaluation and Assessment of Treatment (HEAT) registry from 13 UK centres (2005-2020) was conducted. Five or more years of follow-up was available for 325 (24%) patients. Focal HIFU therapy used a transrectal ultrasound-guided device (Sonablate; Sonacare Inc., Charlotte, NC, USA). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Failure-free survival (FFS) was primarily defined as avoidance of no evidence of disease to require salvage whole-gland or systemic treatment, or metastases or prostate cancer-specific mortality. Differences in FFS between D'Amico risk groups were determined using a log-rank analysis. Adverse events were reported using Clavien-Dindo classification. RESULTS AND LIMITATIONS: The median (interquartile range) age was 66 (60-71) yr and prostate-specific antigen was 6.9 (4.9-9.4) ng/ml with D'Amico intermediate risk in 65% (896/1379) and high risk in 28% (386/1379). The overall median follow-up was 32 (17-58) mo; for those with ≥5 yr of follow-up, it was 82 (72-94). A total of 252 patients had repeat focal treatment due to residual or recurrent cancer; overall 92 patients required salvage whole-gland treatment. Kaplan-Meier 7-yr FFS was 69% (64-74%). Seven-year FFS in intermediate- and high-risk cancers was 68% (95% confidence interval [CI] 62-75%) and 65% (95% CI 56-74%; p = 0.3). Clavien-Dindo >2 adverse events occurred in 0.5% (7/1379). The median 10-yr follow-up is lacking. CONCLUSIONS: Focal HIFU in carefully selected patients with clinically significant prostate cancer, with six and three of ten patients having, respectively, intermediate- and high-risk cancer, has good cancer control in the medium term. PATIENT SUMMARY: Focal high-intensity focused ultrasound treatment to areas of prostate with cancer can provide an alternative to treating the whole prostate. This treatment modality has good medium-term cancer control over 7 yr, although 10-yr data are not yet available.
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Neoplasias da Próstata , Ultrassom Focalizado Transretal de Alta Intensidade , Humanos , Masculino , Recidiva Local de Neoplasia/patologia , Próstata/patologia , Antígeno Prostático Específico , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Terapia de Salvação/métodos , Resultado do Tratamento , Ultrassom Focalizado Transretal de Alta Intensidade/efeitos adversos , Ultrassom Focalizado Transretal de Alta Intensidade/métodosRESUMO
CONTEXT: Advances in systemic agents have increased overall survival for men diagnosed with metastatic prostate cancer. Additional cytoreductive prostate treatments and metastasis-directed therapies are under evaluation. These confer toxicity but may offer incremental survival benefits. Thus, an understanding of patients' values and treatment preferences is important for counselling, decision-making, and guideline development. OBJECTIVE: To perform a systematic review of patients' values, preferences, and expectations regarding treatment of metastatic prostate cancer. EVIDENCE ACQUISITION: The MEDLINE, Embase, and CINAHL databases were systematically searched for qualitative and preference elucidation studies reporting on patients' preferences for treatment of metastatic prostate cancer. Certainty of evidence was assessed using Grading of Recommendation, Assessment, Development and Evaluation (GRADE) or GRADE Confidence in the Evidence from Reviews of Qualitative Research (CERQual). The protocol was registered on PROSPERO as CRD42020201420. EVIDENCE SYNTHESIS: A total of 1491 participants from 15 studies met the prespecified eligibility for inclusion. The study designs included were discrete choice experiments (n = 5), mixed methods (n = 3), and qualitative methods (n = 7). Disease states reported per study were: metastatic castration-resistant prostate cancer in nine studies (60.0%), metastatic hormone-sensitive prostate cancer in two studies (13.3%), and a mixed cohort in four studies (26.6%). In quantitative preference elicitation studies, patients consistently valued treatment effectiveness and delay in time to symptoms as the two top-ranked treatment attributes (low or very low certainty). Patients were willing to trade off treatment-related toxicity for potential oncological benefits (low certainty). In qualitative studies, thematic analysis revealed cancer progression and/or survival, pain, and fatigue as key components in treatment decisions (low or very low certainty). Patients continue to value oncological benefits in making decisions on treatments under qualitative assessment. CONCLUSIONS: There is limited understanding of how patients make treatment and trade-off decisions following a diagnosis of metastatic prostate cancer. For appropriate investment in emerging cytoreductive local tumour and metastasis-directed therapies, we should seek to better understand how this cohort weighs the oncological benefits against the risks. PATIENT SUMMARY: We looked at how men with advanced (metastatic) prostate cancer make treatment decisions. We found that little is known about patients' preferences for current and proposed new treatments. Further studies are required to understand how patients make decisions to help guide the integration of new treatments into the standard of care.
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INTRODUCTION: Systemic therapy with androgen deprivation therapy (ADT) and intensification with agents such as docetaxel, abiraterone acetate and enzalutamide has resulted in improved overall survival in men with de novo synchronous metastatic hormone-sensitive prostate cancer (mHSPC). Novel local cytoreductive treatments and metastasis-directed therapy are now being evaluated. Such interventions may provide added survival benefit or delay the requirement for further systemic agents and associated toxicity but can confer additional harm. Understanding men's preferences for treatment options in this disease state is crucial for patients, clinicians, carers and future healthcare service providers. METHODS: Using a prospective, multicentre discrete choice experiment (DCE), we aim to determine the attributes associated with treatment that are most important to men with mHSPC. Furthermore, we plan to determine men's preferences for, and trade-offs between, the attributes (survival and side effects) of different treatment options including systemic therapy, local cytoreductive approaches (external beam radiotherapy, cytoreductive radical prostatectomy or minimally invasive ablative therapy) and metastases-directed therapies (metastasectomy or stereotactic ablative body radiotherapy). All men with newly diagnosed mHSPC within 4 months of commencing ADT and WHO performance status 0-2 are eligible. Men who have previously consented to a cytoreductive treatment or have developed castrate-resistant disease will be excluded. This study includes a qualitative analysis component, with patients (n=15) and healthcare professionals (n=5), to identify and define the key attributes associated with treatment options that would warrant trade-off evaluation in a DCE. The main phase component planned recruitment is 300 patients over 1 year, commencing in January 2021, with planned study completion in March 2022. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Health Research Authority East of England, Cambridgeshire and Hertfordshire Research Ethics Committee (Reference: 20/EE/0194). Project information will be reported on the publicly available Imperial College London website and the Heath Economics Research Unit (HERU website including the HERU Blog). We will use the social media accounts of IP5-MATTER, Imperial Prostate London, HERU and the individual researchers to disseminate key findings following publication. Findings from the study will be presented at national/international conferences and peer-reviewed journals. Authorship policy will follow the recommendations of the International Committee of Medical Journal Editors. TRIAL REGISTRATION NUMBER: NCT04590976.
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Antagonistas de Androgênios , Neoplasias da Próstata , Acetato de Abiraterona , Atitude , Humanos , Masculino , Estudos Multicêntricos como Assunto , Estudos Observacionais como Assunto , Estudos Prospectivos , Neoplasias da Próstata/tratamento farmacológicoRESUMO
BACKGROUND: Randomised controlled trials (RCTs) for surgical interventions have often proven difficult with calls for innovative approaches. The Imperial Prostate (IP4) Comparative Health Research Outcomes of Novel Surgery in prostate cancer (IP4-CHRONOS) study aims to deliver level 1 evidence on outcomes following focal therapy which involves treating just the tumour rather than whole-gland surgery or radiotherapy. Our aim is to test the feasibility of two parallel RCTs within an overarching strategy that fits with existing patient and physician equipoise and maximises the chances of success and potential benefit to patients and healthcare services. METHODS AND DESIGN: IP4-CHRONOS is a randomised, unblinded multi-centre study, including two parallel randomised controlled trials targeting the same patient population: IP4-CHRONOS-A and IP4-CHRONOS-B. IP4-CHRONOS-A is a 1:1 RCT and the other is a multi-arm, multi-stage (MAMS) RCT starting with three arms and a 1:1:1 randomisation. The two linked RCTs are discussed with patients at the time of consent and the choice of A or B is dependent on physician and patient equipoise. The primary outcome is the feasibility of recruitment, acceptance of randomisation and compliance to allocated arm. RESULTS: This paper describes the statistical analysis plan (SAP) for the feasibility study within IP4-CHRONOS given its innovative approach. Version 1.0 of the SAP has been reviewed by the Trial Steering Committee (TSC), Chief Investigator (CI), Senior Statistician and Trial Statistician and signed off. The study is ongoing and recruiting. Recruitment is scheduled to finish later in 2021. The SAP documents approved methods and analyses that will be conducted. Since this is written in advance of the analysis, we avoid bias arising from prior knowledge of the study data and findings. DISCUSSION: Our feasibility analysis will demonstrate if IP4-CHRONOS is feasible in terms of recruitment, randomisation and compliance, and whether to continue both A and B or just one to the main stage. TRIAL REGISTRATION: ISRCTN ISRCTN17796995 . Registered on 08 October 2019.
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Neoplasias da Próstata , Estudos de Viabilidade , Humanos , Masculino , Neoplasias da Próstata/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: For localised prostate cancer, focal therapy offers an organ-sparing alternative to radical treatments (radiotherapy or prostatectomy). Currently, there is no randomised comparative effectiveness data evaluating cancer control of both strategies. METHODS: Following the eligibility criteria PSA < 20 ng/mL, Gleason score ≤ 7 and T-stage ≤ T2c, we included 830 radical (440 radiotherapy, 390 prostatectomy) and 530 focal therapy (cryotherapy, high-intensity focused ultrasound or high-dose-rate brachytherapy) patients treated between 2005 and 2018 from multicentre registries in the Netherlands and the UK. A propensity score weighted (PSW) analysis was performed to compare failure-free survival (FFS), with failure defined as salvage treatment, metastatic disease, systemic treatment (androgen deprivation therapy or chemotherapy), or progression to watchful waiting. The secondary outcome was overall survival (OS). Median (IQR) follow-up in each cohort was 55 (28-83) and 62 (42-83) months, respectively. RESULTS: At baseline, radical patients had higher PSA (10.3 versus 7.9) and higher-grade disease (31% ISUP 3 versus 11%) compared to focal patients. After PSW, all covariates were balanced (SMD < 0.1). 6-year weighted FFS was higher after radical therapy (80.3%, 95% CI 73.9-87.3) than after focal therapy (72.8%, 95% CI 66.8-79.8) although not statistically significant (p = 0.1). 6-year weighted OS was significantly lower after radical therapy (93.4%, 95% CI 90.1-95.2 versus 97.5%, 95% CI 94-99.9; p = 0.02). When compared in a three-way analysis, focal and LRP patients had a higher risk of treatment failure than EBRT patients (p < 0.001), but EBRT patients had a higher risk of mortality than focal patients (p = 0.008). CONCLUSIONS: Within the limitations of a cohort-based analysis in which residual confounders are likely to exist, we found no clinically relevant difference in cancer control conferred by focal therapy compared to radical therapy at 6 years.
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Neoplasias da Próstata/terapia , Idoso , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Braquiterapia , Crioterapia , Progressão da Doença , Ablação por Ultrassom Focalizado de Alta Intensidade , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Países Baixos , Pontuação de Propensão , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Sistema de Registros , Estudos Retrospectivos , Terapia de Salvação , Taxa de Sobrevida , Reino UnidoRESUMO
INTRODUCTION: Survival in men diagnosed with de novo synchronous metastatic prostate cancer has increased following the use of upfront systemic treatment, using chemotherapy and other novel androgen receptor targeted agents, in addition to standard androgen deprivation therapy (ADT). Local cytoreductive and metastasis-directed interventions are hypothesised to confer additional survival benefit. In this setting, IP2-ATLANTA will explore progression-free survival (PFS) outcomes with the addition of sequential multimodal local and metastasis-directed treatments compared with standard care alone. METHODS: A phase II, prospective, multicentre, three-arm randomised controlled trial incorporating an embedded feasibility pilot. All men with new histologically diagnosed, hormone-sensitive, metastatic prostate cancer, within 4 months of commencing ADT and of performance status 0 to 2 are eligible. Patients will be randomised to Control (standard of care (SOC)) OR Intervention 1 (minimally invasive ablative therapy to prostate±pelvic lymph node dissection (PLND)) OR Intervention 2 (cytoreductive radical prostatectomy±PLND OR prostate radiotherapy±pelvic lymph node radiotherapy (PLNRT)). Metastatic burden will be prespecified using the Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease (CHAARTED) definition. Men with low burden disease in intervention arms are eligible for metastasis-directed therapy, in the form of stereotactic ablative body radiotherapy (SABR) or surgery. Standard systemic therapy will be administered in all arms with ADT±upfront systemic chemotherapy or androgen receptor agents. Patients will be followed-up for a minimum of 2 years. PRIMARY OUTCOME: PFS. Secondary outcomes include predictive factors for PFS and overall survival; urinary, sexual and rectal side effects. Embedded feasibility sample size is 80, with 918 patients required in the main phase II component. Study recruitment commenced in April 2019, with planned follow-up completed by April 2024. ETHICS AND DISSEMINATION: Approved by the Health Research Authority (HRA) Research Ethics Committee Wales-5 (19/WA0005). Study results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03763253; ISCRTN58401737.
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Antagonistas de Androgênios , Neoplasias da Próstata , Algoritmos , Antagonistas de Androgênios/uso terapêutico , Ensaios Clínicos Fase II como Assunto , Humanos , Masculino , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Neoplasias da Próstata/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , País de GalesRESUMO
INTRODUCTION: Focal therapy (FT) ablates areas of prostate cancer rather than treating the whole gland. We compared oncological outcomes of FT to radical prostatectomy (RP). METHODS: Using prospective multicentre databases of 761 FT and 572 RP cases (November/2005-September/2018), patients with PSA < 20 ng/ml, Gleason = 4 + 3 and stage = T2c were 1-1 propensity score-matched for treatment year, age, PSA, Gleason, T-stage, cancer core length and use of neoadjuvant hormones. FT included 1-2 sessions. Primary outcome was failure-free survival (FFS) defined by need for salvage local or systemic therapy or metastases. Differences in FFS were determined using Kaplan-Meier analysis with log-rank test. RESULTS: 335 radical prostatectomy and 501 focal therapy patients were eligible for matching. For focal therapy, 420 had HIFU and 81 cryotherapy. Cryotherapy was used predominantly for anterior cancer. After matching, 246 RP and 246 FT cases were identified. For radical prostatectomy, mean (SD) age was 63.4 (5.6) years, median (IQR) PSA 7.9 g/ml (6-10) and median (IQR) follow-up 64 (30-89) months. For focal therapy, these were 63.3 (6.9) years, 7.9 ng/ml (5.5-10.6) and 49 [34-67] months, respectively. At 3, 5 and 8 years, FFS (95%CI) was 86% (81-91%), 82% (77-88%) and 79% (73-86%) for radical prostatectomy compared to 91% (87-95%), 86% (81-92%) and 83% (76-90%) following focal therapy (p = 0.12). CONCLUSIONS: In patients with non-metastatic low- intermediate prostate cancer, oncological outcomes over 8 years were similar between focal therapy and radical prostatectomy.