Active surveillance of prostate cancer: a questionnaire survey of urologists, clinical oncologists and urology nurse specialists across three cancer networks in the United Kingdom

Abstract Background Active surveillance is considered a mainstream strategy in the management of patients with low-risk prostate cancer. A mission-critical step in implementing a robust active surveillance program and plan its resource and service requirements, is to gauge its current practice across the United Kingdom. Furthermore it is imperative to determine the existing practices in the context of the recommendations suggested by the recent National Institute for Health and Clinical Excellence guidance on active surveillance of prostate cancer. Methods An internet questionnaire was circulated to urologists, clinical oncologists and urology nurse specialists across three geographically distinct cancer networks. Twenty five questions across four domains were assessed. (i) hospital resources (staff and clinical areas) utilised for active surveillance (ii) enrolment criteria (iii) follow up (iv) criteria that trigger conversion to active treatment. Results We received 35 responses, 20 of which were from urologists. The survey data suggests that there is marked heterogeneity in enrolment criteria with patients having features of intermediate-risk prostate cancer often recruited into Active Surveillance programs. Only 60 % of our respondents use multiparametric MRI routinely to assess patient suitability for active surveillance. In addition, marked variation exists in how patients are followed up with regard to PSA testing intervals and timing of repeat biopsies. Only 40 % undertake a repeat biopsy at 12 months. Tumour upgrading on repeat biopsy, an increase in tumour volume or percentage of core biopsies involved would prompt a recommendation for treatment amongst most survey respondents. In addition allocation of resources and services for active surveillance is poor. Currently there are no dedicated active surveillance clinics, which are well-structured, -resourced and -supported for regular patient counselling and follow up. Conclusion This variability in enrolment criteria and follow up is also demonstrated in international and national series of active surveillance. Resources are not currently in place across the UK to support an active surveillance program and a national discussion and debate to plan resources is much required so that it can become a mainstream therapeutic strategy

Active surveillance of prostate cancer: a questionnaire survey of urologists, clinical oncologists and urology nurse specialists across three cancer networks in the United Kingdom.

BACKGROUND: Active surveillance is considered a mainstream strategy in the management of patients with low-risk prostate cancer. A mission-critical step in implementing a robust active surveillance program and plan its resource and service requirements, is to gauge its current practice across the United Kingdom. Furthermore it is imperative to determine the existing practices in the context of the recommendations suggested by the recent National Institute for Health and Clinical Excellence guidance on active surveillance of prostate cancer. METHODS: An internet questionnaire was circulated to urologists, clinical oncologists and urology nurse specialists across three geographically distinct cancer networks. Twenty five questions across four domains were assessed. (i) hospital resources (staff and clinical areas) utilised for active surveillance (ii) enrolment criteria (iii) follow up (iv) criteria that trigger conversion to active treatment. RESULTS: We received 35 responses, 20 of which were from urologists. The survey data suggests that there is marked heterogeneity in enrolment criteria with patients having features of intermediate-risk prostate cancer often recruited into Active Surveillance programs. Only 60 % of our respondents use multiparametric MRI routinely to assess patient suitability for active surveillance. In addition, marked variation exists in how patients are followed up with regard to PSA testing intervals and timing of repeat biopsies. Only 40 % undertake a repeat biopsy at 12 months. Tumour upgrading on repeat biopsy, an increase in tumour volume or percentage of core biopsies involved would prompt a recommendation for treatment amongst most survey respondents. In addition allocation of resources and services for active surveillance is poor. Currently there are no dedicated active surveillance clinics, which are well-structured, -resourced and -supported for regular patient counselling and follow up. CONCLUSION: This variability in enrolment criteria and follow up is also demonstrated in international and national series of active surveillance. Resources are not currently in place across the UK to support an active surveillance program and a national discussion and debate to plan resources is much required so that it can become a mainstream therapeutic strategy

Comparative Oncologic and Toxicity Outcomes of Salvage Radical Prostatectomy Versus Nonsurgical Therapies for Radiorecurrent Prostate Cancer: A Meta-Regression Analysis.

CONTEXT: In the absence of randomised controlled trials comparing the oncologic, toxicity, and functional outcomes of salvage radical prostatectomy (SRP), salvage high-intensity focused ultrasound (SHIFU), salvage brachytherapy (SBT), and salvage cryotherapy (SCT), controversy exists as to the optimal salvage modality in radiorecurrent prostate cancer. OBJECTIVE: We carried out a meta-regression analysis to determine whether there is a difference in oncologic, toxicity, and functional outcomes using data from original publications of salvage modalities in the postradiation setting. EVIDENCE ACQUISITION: We performed a systematic review of PubMed/Medline citations according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. We included 63 articles in the analysis (25 on SRP, 8 on SHIFU, 16 on SCT, 14 on SBT). EVIDENCE SYNTHESIS: Median values of the following variables were extracted from each study: patient age, length of follow-up, prostate-specific antigen (PSA) before radiotherapy (RT), PSA before salvage therapy, Gleason score before RT, and time interval between RT and salvage therapy. Functional, toxicity, and oncologic outcomes were measured according to rates of impotence, incontinence, fistula formation, urethral strictures, and biochemical recurrence. Meta-regression adjusting for confounders found no significant difference in oncologic outcomes between SRP and nonsurgical salvage modalities. SBT, SCT, and SHIFU appeared to have better continence outcomes than SRP. No significant difference in toxicity outcomes between modalities was found, although limitations such as reporting, selection, and publication bias and between-study heterogeneity must also be considered with these conclusions. CONCLUSIONS: Oncologic outcomes are comparable for SRP and all three nonsurgical salvage modalities. We found no significant differences in toxicity outcomes among modalities; however, SRP appears to be associated with worse rates of urinary incontinence than SBT, SCT, and SHIFU. PATIENT SUMMARY: We performed a meta-regression analysis to compare oncologic, functional, and toxicity outcomes between salvage radical prostatectomy and nonsurgical salvage modalities. Oncologic and toxicity outcomes appear to be similar; however, all nonsurgical salvage modalities may be associated with better continence outcomes.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.euf.2015.09.00

Molecular analysis of archival diagnostic prostate cancer biopsies identifies genomic similarities in cases with progression post-radiotherapy, and those with de novo metastatic disease

Purpose It is important to identify molecular features that improve prostate cancer (PCa) risk stratification before radical treatment with curative intent. Molecular analysis of historical diagnostic formalin-fixed paraffin-embedded (FFPE) prostate biopsies from cohorts with post-radiotherapy (RT) long-term clinical follow-up has been limited. Utilizing parallel sequencing modalities, we performed a proof-of-principle sequencing analysis of historical diagnostic FFPE prostate biopsies. We compared patients with i) stable PCa post-primary or salvage RT (sPCa), ii) progressing PCa post-RT (pPCa), and iii) de novo metastatic PCa (mPCa). Experimental Design A cohort of 19 patients with diagnostic prostate biopsies (n=6 sPCa, n=5 pPCa, n=8 mPCa) and mean 4 years 10 months follow-up (diagnosed 2009-2016) underwent nucleic acid extraction from demarcated malignancy. Samples underwent 3’RNA sequencing (3’RNAseq) (n=19), nanoString analysis (n=12) and Illumina 850k methylation (n=8) sequencing. Bioinformatic analysis was performed to coherently identify differentially expressed genes (DEGs) and methylated genomic regions (MGRs). Results 18 of 19 samples provided useable 3’RNAseq data. Principal Component Analysis (PCA) demonstrated similar expression profiles between pPCa and mPCa cases, versus sPCa. Coherently differentially methylated probes between these groups identified ∼600 differentially MGRs. The top 50 genes with increased expression in pPCa patients were associated with reduced progression-free survival post-RT (p<0.0001) in an external cohort. Conclusions 3’RNAseq, nanoString and 850K-methylation analyses are each achievable from historical FFPE diagnostic pre-treatment prostate biopsies, unlocking the potential to utilize large cohorts of historic clinical samples. Profiling similarities between individuals with pPCa and mPCa suggests biological similarities and historical radiological staging limitations, which warrant further investigation

Molecular analysis of archival diagnostic prostate cancer biopsies identifies genomic similarities in cases with progression post-radiotherapy, and those with de novo metastatic disease

Background: It is important to identify molecular features that improve prostate cancer (PCa) risk stratification before radical treatment with curative intent. Molecular analysis of historical diagnostic formalin-fixed paraffin-embedded (FFPE) prostate biopsies from cohorts with post-radiotherapy (RT) long-term clinical follow-up has been limited. Utilizing parallel sequencing modalities, we performed a proof-of-principle sequencing analysis of historical diagnostic FFPE prostate biopsies. We compared patients with (i) stable PCa (sPCa) postprimary or salvage RT, (ii) progressing PCa (pPCa) post-RT, and (iii) de novo metastatic PCa (mPCa). Methods: A cohort of 19 patients with diagnostic prostate biopsies (n = 6 sPCa, n = 5 pPCa, n = 8 mPCa) and mean 4 years 10 months follow-up (diagnosed 2009–2016) underwent nucleic acid extraction from demarcated malignancy. Samples underwent 3′RNA sequencing (3′RNAseq) (n = 19), nanoString analysis (n = 12), and Illumina 850k methylation (n = 8) sequencing. Bioinformatic analysis was performed to coherently identify differentially expressed genes and methylated genomic regions (MGRs). Results: Eighteen of 19 samples provided useable 3′RNAseq data. Principal component analysis (PCA) demonstrated similar expression profiles between pPCa and mPCa cases, versus sPCa. Coherently differentially methylated probes between these groups identified ~600 differentially MGRs. The top 50 genes with increased expression in pPCa patients were associated with reduced progression-free survival post-RT (p < 0.0001) in an external cohort. Conclusions: 3′RNAseq, nanoString and 850k-methylation analyses are each achievable from historical FFPE diagnostic pretreatment prostate biopsies, unlocking the potential to utilize large cohorts of historic clinical samples. Profiling similarities between individuals with pPCa and mPCa suggests biological similarities and historical radiological staging limitations, which warrant further investigation

No surgical innovation without evaluation : evolution and further development of the IDEAL Framework and Recommendations

OBJECTIVE: To update, clarify, and extend IDEAL concepts and recommendations. BACKGROUND: New surgical procedures, devices, and other complex interventions need robust evaluation for safety, efficacy, and effectiveness. Unlike new medicines, there is no internationally agreed evaluation pathway for generating and analyzing data throughout the life cycle of surgical innovations. The IDEAL Framework and Recommendations were designed to provide this pathway and they have been used increasingly since their introduction in 2009. Based on a Delphi survey, expert workshop and major discussions during IDEAL conferences held in Oxford (2016) and New York (2017), this article updates and extends the IDEAL Recommendations, identifies areas for future research, and discusses the ethical problems faced by investigators at each IDEAL stage. METHODS: The IDEAL Framework describes 5 stages of evolution for new surgical therapeutic interventions-Idea, Development, Exploration, Assessment, and Long-term Study. This comprehensive update proposes several modifications. First, a "Pre-IDEAL" stage describing preclinical studies has been added. Second we discuss potential adaptations to expand the scope of IDEAL (originally designed for surgical procedures) to accommodate therapeutic devices, through an IDEAL-D variant. Third, we explicitly recognise the value of comprehensive data collection through registries at all stages in the Framework and fourth, we examine the ethical issues that arise at each stage of IDEAL and underpin the recommendations. The Recommendations for each stage are reviewed, clarified and additional detail added. CONCLUSIONS: The intention of this article is to widen the practical use of IDEAL by clarifying the rationale for and practical details of the Recommendations. Additional research based on the experience of implementing these Recommendations is needed to further improve them

Localised prostate cancer: clinical and cost-effectiveness of new and emerging technologies

In contrast to pharmacological interventions that undergo rigorous clinical testing, recent technological advances in the treatment of prostate cancer (PCa) have particularly been introduced and driven by economic incentives rather than high-quality clinical evidence. In this review we summarise the clinical and cost-effectiveness of new and emerging technologies for localised PCa. We emphasise particularly on robotic prostatectomy, new developments in radiotherapy, novel technologies in focal therapy such as cryosurgery and high-intensity focused ultrasound (HIFU). Robotic-assisted laparoscopic radical prostatectomy (RALRP) has similar oncologic outcomes to open radical retropubic prostatectomy (RRP); however, patients who undergo RALRP are more likely to have improved short-term potency rates. Intensity-modulated radiotherapy (IMRT) and proton-beam therapy (PBT) have similar oncologic outcomes to external-beam radiotherapy (EBRT). IMRT has exhibited an improved gastrointestinal side effect profile compared to EBRT. PBT is not cost-effective compared to other radiotherapy modalities. Early studies of focal therapies in localised PCa have yielded positive results. Treatment decisions should be driven by cancer risk and patient preference rather than by financial incentives or availability of technology.</p