There is uncertainty in deferred active treatment (DAT) programmes, regarding patient selection, follow-up and monitoring, reclassification, and which outcome measures should be prioritised.
To ...develop consensus statements for all domains of DAT.
A protocol-driven, three phase study was undertaken by the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Association of Urology Section of Urological Research (ESUR)-International Society of Geriatric Oncology (SIOG) Prostate Cancer Guideline Panel in conjunction with partner organisations, including the following: (1) a systematic review to describe heterogeneity across all domains; (2) a two-round Delphi survey involving a large, international panel of stakeholders, including healthcare practitioners (HCPs) and patients; and (3) a consensus group meeting attended by stakeholder group representatives. Robust methods regarding what constituted the consensus were strictly followed.
A total of 109 HCPs and 16 patients completed both survey rounds. Of 129 statements in the survey, consensus was achieved in 66 (51%); the rest of the statements were discussed and voted on in the consensus meeting by 32 HCPs and three patients, where consensus was achieved in additional 27 statements (43%). Overall, 93 statements (72%) achieved consensus in the project. Some uncertainties remained regarding clinically important thresholds for disease extent on biopsy in low-risk disease, and the role of multiparametric magnetic resonance imaging in determining disease stage and aggressiveness as a criterion for inclusion and exclusion.
Consensus statements and the findings are expected to guide and inform routine clinical practice and research, until higher levels of evidence emerge through prospective comparative studies and clinical trials.
We undertook a project aimed at standardising the elements of practice in active surveillance programmes for early localised prostate cancer because currently there is great variation and uncertainty regarding how best to conduct them. The project involved large numbers of healthcare practitioners and patients using a survey and face-to-face meeting, in order to achieve agreement (ie, consensus) regarding best practice, which will provide guidance to clinicians and researchers.
The European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Association of Urology Section of Urological Research (ESUR)-International Society of Geriatric Oncology (SIOG) Prostate Cancer Guideline Panel in conjunction with partner organisations has developed comprehensive consensus statements for deferred active treatment for localised prostate cancer covering all domains, aimed at guiding and informing routine clinical practice and research.
Purpose
Genitourinary (GU) multidisciplinary tumour boards (GUMTBs) are key components of patient care, as they might lead to changes in treatment plan, improved survival, and increased adherence to ...guidelines. However, there are no guidelines on how GUMTBs should operate or how to assess their quality of performance.
Methods
A systematic literature review was conducted to identify criteria and indicators to evaluate quality in GUMTBs. A scientific committee—comprising 12 GU cancer specialists from seven disciplines—proposed a list of criteria and developed indicators, evaluated in two rounds of Delphi method. Appropriateness and utility of indicators were scored using a 9-point Likert scale. Consensus was defined as at least two-thirds of Delphi respondents selecting a score sub-category that encompassed the median score of the group.
Results
Forty-five criteria were selected to evaluate the quality of GUMTBs covering five dimensions: organisation, personnel, protocol and documentation, resources, and interaction with patients. Then, 33 indicators were developed and evaluated in the first round of Delphi, leading to a selection of 26 indicators in two dimensions: function, governance and resources, and GUMTB sessions. In the second round, consensus was reached on the appropriateness of all 26 indicators and on the utility of 24 of them. Index cards for criteria and indicators were developed to be used in clinical practice.
Conclusions
Criteria and indicators were developed to evaluate the quality of GUMTBs, aiming to serve as a guide to improve quality of care and health outcomes in patients with GU cancer.
Approximately 30% of patients who undergo radical prostatectomy for prostate cancer develop disease progression. The only potentially curative treatment in these patients is postoperative ...radiotherapy with or without hormonotherapy. One of the standards of care in nonsurgical patients is hypofractionated radiotherapy. However, the current evidence based is insufficient to define the optimal dose and fractionation schedule for postoperative radiotherapy. In this context, the aim of this editorial is to assess the main efficacy and toxicity data for postoperative hypofractionated radiotherapy and discuss the potential to implement this fractionation in routine clinical practice.
Radiation-induced cystitis is a common side effect of radiotherapy (RT) to the pelvic area. Hyaluronic acid (HA) and chondroitin sulfate (CS) are components of the urothelial mucosa and positive ...results have been obtained for intravesical HA/CS instillations for the treatment of urinary tract infections and bladder pain syndrome. HA/CS may also have a protective effect against RT bladder toxicity.
To investigate whether HA and CS protect the urothelium during RT, alleviate lower urinary tract symptoms, and improve quality of life.
This multicentre randomised controlled trial was conducted across seven centres in four countries. Male patients aged ≥18 yr scheduled to undergo primary intensity-modulated radiotherapy for localised prostate cancer were enrolled.
Patients were randomised to intravesical HA/CS plus an oral formulation of curcumin, quercetin, HA, and CS (group A) or no treatment (group B).
The primary endpoint was absolute changes from baseline to follow-up in urinary domain scores for the Expanded Prostate Cancer Index Composite (EPIC), the International Consultation on Incontinence Questionnaire-Male Lower Urinary Tract Symptoms (ICIQ-MLUTS), and the EuroQol Group EQ-5D-5L questionnaire. Data analysis for efficacy and safety outcomes was performed using an intention-to-treat (ITT) approach; the ITT population was defined as all randomised patients.
Of 57 patients screened, 49 were enrolled and randomly assigned to either active treatment (group A, n = 25) or the control (group B, n = 24). Three patients in the control group withdrew after randomisation. Changes from baseline to 12 mo were worse in the control group for subtotal scores for urinary symptoms and impact of symptoms on quality of life and for the total score (p = 0.05, p = 0.003, and p = 0.008, respectively). There was a significant time × group interaction in favour of active treatment for the incontinence symptom score (p = 0.011) and bother score (p = 0.017). The absence of a sham procedure and/or placebo is the main limitation.
Our results suggest that intravesical HA/CS in combination with an oral formulation may reduce urinary symptoms and improve QoL at short-term (1 yr) follow-up.
We investigated whether hyaluronic acid (HA) and chondroitin sulfate (CS) have a protective effect against the bladder toxicity of radiotherapy for prostate cancer. HA/CS used for weekly bladder irrigation for 6 wk and given orally with curcumin and quercetin for 12 wk reduced urinary incontinence symptoms and bother measured at 1-year follow-up. This may hold promise as a preventive treatment if the results are confirmed in further trials.
Our findings show a beneficial effect of intravesical hyaluronic acid (HA)/chondroitin sulfate (SC) plus the oral combination of curcumin, quercetin, HA, and CS for prevention of acute and late (1 yr) radiation-induced cystitis and improvement in quality of life. The current strategy may have a place among treatment options for the prevention of radiation-induced bladder complications, which until now have been limited to symptom-relieving and temporary modalities.
Late onset of radiation-induced haemorrhagic cystitis (RHC) after radiation therapy (RT) for prostate cancer (PCa) may present or evolve severely, requiring hospitalization with invasive ...interventions. In the present study, we have analysed the prevalence and risk factors associated with the onset of RHC.
From January 2002 to May 2017, 1421 patients undertook RT for PCa as a primary, adjuvant, or salvage treatment option. RHC presented in 5.6% (n = 80) of the patients; the diagnosis was based on clinical and endoscopic characteristics. Variables in observation included patients, tumours, and RT-dosimetry characteristics. Patients with a previous history of bladder cancer were excluded. Univariate (Student t/Chi square) and uni-/multivariate Cox regression analysis were performed; the events and time-points were hospitalization and time-to-event, respectively.
There were 80 patients with a mean age at RT of 70.1 years (SD 6.4), mean time lag to RHC of 43.9 months (SD 37.5). Median Emergency attendance was two and three times for patients without/with hospitalization, respectively. There were in total 64 admissions with invasive treatment required in 26/36 (72.2%) of the patients hospitalised, including transurethral fulguration in 22 and radical cystectomy in 5. Patients at higher risk of hospitalization were those undertaking antiplatelet/anticoagulant treatment (HR:3.30; CI 95%:1.53–3.30; p = 0.002) and those treated with salvage RT with higher bladder volume receiving >70 Gy (bladder V70) (HR:1.03; CI 95%:1.01–1.05; p = 0.027). At receiving operating characteristic analysis, the cutoff for bladder V70 was 29%.
Nearly half of patients presenting RHC may require invasive treatment including cystectomy. Risk factors associated with hospitalization are patients undertaking antiplatelet/coagulant treatment and bladder V70 > 29% in salvage RT patients.
Abstract Background Prostate cancer (PCa) is an androgen-dependent disease. Nonetheless, the role of single nucleotide polymorphisms (SNPs) in genes encoding androgen metabolism remains an unexplored ...area. Purpose To investigate the role of germline variations in cytochrome P450 17A1 ( CYP17A1 ) and steroid-5α-reductase, α-polypeptides 1 and 2 ( SRD5A1 and SRD5A2 ) genes in PCa. Patients and methods In total, 494 consecutive Spanish patients diagnosed with nonmetastatic localized PCa were included in this multicenter study and were genotyped for 32 SNPs in SRD5A1, SRD5A2, and CYP17A1 genes using a Biotrove OpenArray NT Cycler. Clinical data were available. Genotypic and allelic frequencies, as well as haplotype analyses, were determined using the web-based environment SNPator. All additional statistical analyses comparing clinical data and SNPs were performed using PASW Statistics 15. Results The call rate obtained (determined as the percentage of successful determinations) was 97.3% of detection. A total of 2 SNPs in SRD5A1 —rs3822430 and rs1691053—were associated with prostate-specific antigen level at diagnosis. Moreover, G carriers for both SNPs were at higher risk of presenting initial prostate-specific antigen levels>20 ng/ml (Exp( B ) = 2.812, 95% CI: 1.397–5.657, P = 0.004) than those who are AA-AA carriers. Haplotype analyses showed that patients with PCa nonhomozygous for the haplotype GCTTGTAGTA were at an elevated risk of presenting bigger clinical tumor size (Exp( B ) = 3.823, 95% CI: 1.280–11.416, P = 0.016), and higher Gleason score (Exp( B ) = 2.808, 95% CI: 1.134–6.953, P = 0.026). Conclusions SNPs in SRD5A1 seem to affect the clinical characteristics of Spanish patients with PCa.
Brachytherapy (BT) is widely used for salvage therapy in patients with biochemical failure (BF) after radiotherapy for prostate cancer (PCa). Although low-dose-rate (LDR) and high-dose-rate (HDR) BT ...are both used for salvage therapy, it is not clear whether there are any differences between these two approaches in terms of efficacy or toxicity in this setting. Therefore, we review the institutional experience of the members of the Urological Tumour Working Group (URONCOR) of the Spanish Society of Radiation Oncology (SEOR) to compare these two techniques.
Between 2001 and 2016, 119 patients with biopsy-proven, locally-recurrent PCa underwent salvage BT (LDR, n = 44; HDR, n = 75) after primary radiotherapy. Relapse-free survival (RFS) and cause-specific survival (CSS) after salvage therapy were analyzed. Toxicity was assessed according to the RTOG scale.
Median follow-up after salvage BT was 52 months. Overall, the 5-year prostate-specific antigen (PSA) RFS rate was 71% (95% CI, 65.9%–75.9%). No significant between-group differences in RFS were observed (p = 0.063). Five-year CSS for the LDR- and HDR-BT groups were 96.5% and 93%, respectively. Overall, 38 patients (32%) developed biochemical progression (Phoenix definition) after salvage BT: 14 patients (32%) in the LDR group and 24 (32.5%) in the HDR group. On the multivariate analysis, the following variables were significantly associated with progression, time to BF from primary radiotherapy <30 months (p = 0.014); and post-salvage nadir PSA (p = 0.000). There were no significant between-group differences in toxicity. Overall, there were 13 cases of urethral stricture, 22 cases of urinary incontinence, and 13 cases of haematuria. Toxicity ≥grade 3 was observed in 23.5% of patients.
These findings show that both HDR-BT and LDR-BT yield comparable efficacy and toxicity outcomes in patients undergoing salvage treatment for locally-recurrent prostate cancer after primary radiotherapy. Predictors of worse outcomes after salvage BT were post-salvage nadir PSA and time to BF from initial radiotherapy.
Differences in the distribution of genotypes between individuals of the same ethnicity are an important confounder factor commonly undervalued in typical association studies conducted in ...radiogenomics.
To evaluate the genotypic distribution of SNPs in a wide set of Spanish prostate cancer patients for determine the homogeneity of the population and to disclose potential bias.
A total of 601 prostate cancer patients from Andalusia, Basque Country, Canary and Catalonia were genotyped for 10 SNPs located in 6 different genes associated to DNA repair: XRCC1 (rs25487, rs25489, rs1799782), ERCC2 (rs13181), ERCC1 (rs11615), LIG4 (rs1805388, rs1805386), ATM (rs17503908, rs1800057) and P53 (rs1042522). The SNP genotyping was made in a Biotrove OpenArray® NT Cycler.
Comparisons of genotypic and allelic frequencies among populations, as well as haplotype analyses were determined using the web-based environment SNPator. Principal component analysis was made using the SnpMatrix and XSnpMatrix classes and methods implemented as an R package. Non-supervised hierarchical cluster of SNP was made using MultiExperiment Viewer.
We observed that genotype distribution of 4 out 10 SNPs was statistically different among the studied populations, showing the greatest differences between Andalusia and Catalonia. These observations were confirmed in cluster analysis, principal component analysis and in the differential distribution of haplotypes among the populations. Because tumor characteristics have not been taken into account, it is possible that some polymorphisms may influence tumor characteristics in the same way that it may pose a risk factor for other disease characteristics.
Differences in distribution of genotypes within different populations of the same ethnicity could be an important confounding factor responsible for the lack of validation of SNPs associated with radiation-induced toxicity, especially when extensive meta-analysis with subjects from different countries are carried out.
The Bladder Cancer Index (BCI) is so far the only instrument applicable across all bladder cancer patients, independent of tumor infiltration or treatment applied. We developed a Spanish version of ...the BCI, and assessed its acceptability and metric properties.
For the adaptation into Spanish we used the forward and back-translation method, expert panels, and cognitive debriefing patient interviews. For the assessment of metric properties we used data from 197 bladder cancer patients from a multi-center prospective study. The Spanish BCI and the SF-36 Health Survey were self-administered before and 12 months after treatment. Reliability was estimated by Cronbach's alpha. Construct validity was assessed through the multi-trait multi-method matrix. The magnitude of change was quantified by effect sizes to assess responsiveness.
Reliability coefficients ranged 0.75-0.97. The validity analysis confirmed moderate associations between the BCI function and bother subscales for urinary (r = 0.61) and bowel (r = 0.53) domains; conceptual independence among all BCI domains (r ≤ 0.3); and low correlation coefficients with the SF-36 scores, ranging 0.14-0.48. Among patients reporting global improvement at follow-up, pre-post treatment changes were statistically significant for the urinary domain and urinary bother subscale, with effect sizes of 0.38 and 0.53.
The Spanish BCI is well accepted, reliable, valid, responsive, and similar in performance compared to the original instrument. These findings support its use, both in Spanish and international studies, as a valuable and comprehensive tool for assessing quality of life across a wide range of bladder cancer patients.
Besides serum levels of PSA, there is a lack of prostate cancer specific biomarkers. It is need to develop new biological markers associated with the tumor behavior which would be valuable to better ...individualize treatment. The aim of this study was to elucidate the relationship between single nucleotide polymorphisms (SNPs) in genes involved in DNA repair and prostate cancer progression.
A total of 494 prostate cancer patients from a Spanish multicenter study were genotyped for 10 SNPs in XRCC1, ERCC2, ERCC1, LIG4, ATM and TP53 genes. The SNP genotyping was made in a Biotrove OpenArray® NT Cycler. Clinical tumor stage, diagnostic PSA serum levels, and Gleason score at diagnosis were obtained for all participants. Genotypic and allelic frequencies were determined using the web-based environment SNPator.
SNPs rs11615 (ERCC1) and rs17503908 (ATM) appeared as risk factors for prostate cancer aggressiveness. Patients wild homozygous for these SNPs (AA and TT, respectively) were at higher risk for developing cT2b - cT4 (OR = 2.21 (confidence interval (CI) 95% 1.47 - 3.31), p < 0.001) and Gleason scores ≥ 7 (OR = 2.22 (CI 95% 1.38 - 3.57), p < 0.001), respectively. Moreover, those patients wild homozygous for both SNPs had the greatest risk of presenting D'Amico high-risk tumors (OR = 2.57 (CI 95% 1.28 - 5.16)).
Genetic variants at DNA repair genes are associated with prostate cancer progression, and would be taken into account when assessing the malignancy of prostate cancer.
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