Trends in Diagnosis and Disparities in Initial Management of High-Risk Prostate Cancer in the US
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ABSTRACT:
SUBMITTER: Agrawal V
PROVIDER: S-EPMC7489870 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
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Project description:Recent advances have seen a surge of new ideas and technologies to aid in the detection, treatment and further understanding of glaucoma. These technologies and advances are discussed to provide information on risk-factors, diagnosis and treatment. Glaucoma has never before seen such an advance in research and therapies coming forward in to the clinical workplace. It is an exciting time for physicians and researchers alike and over the next decade will certainly see advances in early detection, efficacious treatments and neuroprotection.
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Project description:Prostate cancer remains the leading diagnosed cancer and the second leading cause of death among American men. Despite improvements in screening modalities, diagnostics, and treatment, disparities exist among Black men in this country. The primary objective of this systematic review is to describe the reported disparities in screening, diagnostics, and treatments as well as efforts to alleviate these disparities through community and educational outreach efforts. Critical review took place of retrospective, prospective, and socially descriptive data of English language publications in the PubMed database. Despite more advanced presentation, lower rates of screening and diagnostic procedures, and low rates of trial inclusion, subanalyses have shown that various modalities of therapy are quite effective in Black populations. Moreover, patients treated on prospective clinical trials and within equal-access care environments have shown similar outcomes regardless of race. Additional prospective studies and enhanced participation in screening, diagnostic and genetic testing, clinical trials, and community-based educational endeavors are important to ensure equitable progress in prostate cancer for all patients. IMPLICATIONS FOR PRACTICE: Notable progress has been made with therapeutic advances for prostate cancer, but racial disparities continue to exist. Differing rates in screening and utility in diagnostic procedures play a role in these disparities. Black patients often present with more advanced disease, higher prostate-specific antigen, and other adverse factors, but outcomes can be attenuated in trials or in equal-access care environments. Recent data have shown that multiple modalities of therapy are quite effective in Black populations. Novel and bold hypotheses to increase inclusion in clinical trial, enhance decentralized trial efforts, and enact successful models of patient navigation and community partnership are vital to ensure continued progress in prostate cancer disparities.
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Project description:OBJECTIVE:To evaluate the effect of adding multiparametric magnetic resonance imaging (mpMRI) to pre-surgical planning on surgical decision making for the management of high-risk prostate cancer (HRPC). PATIENTS AND METHODS:A survey was designed to query multiple centers on surgical decisions of 41 consecutive HRPC cases seen from 2012 to 2015. HRPC was defined by the National Comprehensive Cancer Center Network guidelines. Six fellowship-trained urologic oncologists were asked for their surgical plan in regards to the degree of planned nerve-sparing and lymph node dissection. Two rounds of surveys were administered to six external urologic oncologists. The first survey included the case description only and the second included case description with mpMRI images and report. The correct surgical plan was analyzed by correlation of the degree of planned surgical excision and consistency with the final pathologic evaluation. A priori, an effect size of 20% change was used to determine statistical significance, at p?<?0.05. RESULTS:All cases had at least one change to surgical planning after mpMRI review. Forty (98%) patients had a change in the degree of planned nerve sparing: wider excision in 32% and increased nerve sparing in 24%. After mpMRI the correct surgical plan change was made in 49% for the right and left 51%, decreasing the potential for positive margins. Lymph node dissection was altered from standard to extended lymph node dissection in 17%. CONCLUSIONS:Although mpMRI is not integrated in guidelines for preoperative planning in HRPC, its use may impact surgical planning, cancer control, and quality of life.
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Project description:Purpose: Prostatectomy is one of the main therapeutic options for prostate cancer (PCa). Studies proved the benefit of adjuvant radiotherapy (aRT) on clinical outcomes, with more toxicities when compared to salvage radiotherapy. A better assessment of the likelihood of biochemical recurrence (BCR) would rationalize performing aRT. Our goal was to assess the prognostic value of MRI-derived radiomics on BCR for PCa with high recurrence risk. Methods: We retrospectively selected patients with a high recurrence risk (T3a/b or T4 and/or R1 and/or Gleason score>7) and excluded patients with a post-operative PSA > 0.04 ng/mL or a lymph-node involvement. We extracted IBSI-compliant radiomic features (shape and first order intensity metrics, as well as second and third order textural features) from tumors delineated in T2 and ADC sequences. After random division (training and testing sets) and machine learning based feature reduction, a univariate and multivariate Cox regression analysis was performed to identify independent factors. The correlation with BCR was assessed using AUC and prediction of biochemical relapse free survival (bRFS) with a Kaplan-Meier analysis. Results: One hundred seven patients were included. With a median follow-up of 52.0 months, 17 experienced BCR. In the training set, no clinical feature was correlated with BCR. One feature from ADC (SZEGLSZM) outperformed with an AUC of 0.79 and a HR 17.9 (p = 0.0001). Lower values of SZEGLSZM are associated with more heterogeneous tumors. In the testing set, this feature remained predictive of BCR and bRFS (AUC 0.76, p = 0.0236). Conclusion: One radiomic feature was predictive of BCR and bRFS after prostatectomy helping to guide post-operative management.
| S-EPMC6719613 | biostudies-literature
Project description:What's known on the subject? and What does the study add? Most men who are diagnosed with favourable-risk prostate cancer undergo some form of active intervention, despite evidence that treatment will not improve health outcomes for many. The decision to undergo treatment after diagnosis is, in part, related to the inability to precisely determine the long-term risk of harm without treatment. Nevertheless, physicians should consider patient age, overall health, and preferences for living with cancer and the potential side effects of curative treatments, before recommending a management option. This is especially important for older men, given the high level of evidence that those with low-risk disease are unlikely to accrue any benefit from curative intervention. What is known on the subject: Over treatment of favourable-risk prostate cancer is common, especially among older men. What does the study add: A review of the natural history of favourable-risk prostate cancer in the context of choices for management of the disease. •?The management of favourable-risk prostate cancer is controversial, and in the absence of controlled trials to inform best practice, choices are driven by personal beliefs with resultant wide variation in practice patterns. •?Men with favourable-risk prostate cancer diagnosed today often undergo treatments that will not improve overall health outcomes. •?A shared-decision approach for selecting optimal management of favourable-risk disease should account for patient age, overall health, and preferences for living with cancer and the potential side effects of curative treatments.
| S-EPMC4086468 | biostudies-literature
Project description:ImportanceSurgery after initial lumpectomy to obtain more widely clear margins is common and may lead to mastectomy.ObjectiveTo describe surgeons' approach to surgical margins for invasive breast cancer, and changes in postlumpectomy surgery rates, and final surgical treatment following a 2014 consensus statement endorsing a margin of "no ink on tumor."Design, setting, and participantsThis was a population-based cohort survey study of 7303 eligible women ages 20 to 79 years with stage I and II breast cancer diagnosed in 2013 to 2015 and identified from the Georgia and Los Angeles County, California, Surveillance, Epidemiology, and End Results registries. A total of 5080 (70%) returned a survey. Those with bilateral disease, missing stage or treatment data, and with ductal carcinoma in situ were excluded, leaving 3729 patients in the analytic sample; 98% of these identified their attending surgeon. Between April 2015 and May 2016, 488 surgeons were surveyed regarding lumpectomy margins; 342 (70%) responded completely. Pathology reports of all patients having a second surgery and a 30% sample of those with 1 surgery were reviewed. Time trends were analyzed with multinomial regression models.Main outcomes and measuresRates of final surgical procedure (lumpectomy, unilateral mastectomy, bilateral mastectomy) and rates of additional surgery after initial lumpectomy over time, and surgeon attitudes toward an adequate lumpectomy margin.ResultsThe 67% rate of initial lumpectomy in the 3729 patient analytic sample was unchanged during the study. The rate of final lumpectomy increased by 13% from 2013 to 2015, accompanied by a decrease in unilateral and bilateral mastectomy (P = .002). Surgery after initial lumpectomy declined by 16% (P < .001). Pathology review documented no significant association between date of treatment and positive margins. Of 342 responding surgeons, 69% endorsed a margin of no ink on tumor to avoid reexcision in estrogen receptor-positive progesterone receptor-positive cancer and 63% for estrogen receptor-negative progesterone- receptor-negative cancer. Surgeons treating more than 50 breast cancers annually were significantly more likely to report this margin as adequate (85%; n = 105) compared with those treating 20 cases or fewer (55%; n = 131) (P < .001).Conclusions and relevanceAdditional surgery after initial lumpectomy decreased markedly from 2013 to 2015 concomitant with dissemination of clinical guidelines endorsing a minimal negative margin. These findings suggest that surgeon-led initiatives to address potential overtreatment can reduce the burden of surgical management in patients with cancer.
| S-EPMC5710510 | biostudies-literature
Project description:Introduction:Dose escalation to dominant intraprostatic lesions (DILs) is a novel method to increase the therapeutic ratio in localised prostate cancer. The Stereotactic Prostate Augmented Radiotherapy with Cyberknife (SPARC) trial was designed to determine the feasibility of a focal boost defined with multiparametric magnetic resonance imaging (mpMRI) using stereotactic ablative body radiotherapy (SABR). Materials and methods:Patients were included with newly diagnosed intermediate to high risk prostate cancer with at least one of: Gleason score 4 + 3, stage T3a, or PSA > 20 ng/ml. Visible disease on mpMRI was mandatory and up to 2 separate nodules were allowed. All patients received androgen deprivation. Patients received 36.25 Gy in 5 fractions using CyberKnife® and the DIL received a simultaneous boost to a maximum of 47.5 Gy, as allowed by OAR constraints. Genitourinary (GU) and gastrointestinal (GI) toxicity was reported using the RTOG scoring criteria. International Index of Erectile Function (IIEF) and EQ-5D global health scores were regularly captured. Results:An interim safety analysis was performed on the first 8 patients, recruited between July 2013 and December 2015. Median follow up was 56 months (range 50-74). Median D95 values for the prostate PTV and boost volume were 36.55 Gy (range 35.87-36.99) and 46.62 Gy (range 44.85-48.25) respectively. Of the dose constraints, 10/80 were not achieved but all were minor dose variations. Grade 2+ acute GU and GI toxicities were 37.5% respectively while grade 2+ late GU and GI toxicities were 12.5% and 0% respectively. IIEF and quality of life scores recovered over time and all patients remain in biochemical remission. Conclusion:The first patients have been successfully treated with prostate SABR and focal boost on the SPARC trial, with excellent adherence to the planning protocol. Toxicity and efficacy results are promising and further recruitment is underway.
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Project description:Uveal melanoma, which is the most common primary intraocular malignancy in adults, arises from melanocytes within the iris, ciliary body and choroid. The diagnosis is based principally on clinical examination of the tumor with biomicroscopy and indirect ophthalmoscopy and confirmed by diagnostic techniques such as ultrasonography, fundus fluorescein angiography and optical coherence tomography. The clinical diagnosis of posterior uveal melanomas can be made when the classical appearance of a pigmented dome-shaped mass is detected on dilated fundus exam. Uveal melanomas classically show low to medium reflectivity on A-scan ultrasonography and on B-scan ultrasonography the tumor appears as a hyperechoic, acoustically hollow intraocular mass. Management of a suspicious pigmented lesion is determined by its risk factors of transforming into a choroidal melanoma, such as documentation of growth, thickness greater than 2 mm, presence of subretinal fluid, symptoms and orange pigment, margin within 3 mm of the optic disc, and absence of halo and drusen. Advances in the diagnosis and local and systemic treatment of uveal melanoma have caused a shift from enucleation to eye-conserving treatment modalities including transpupillary thermotherapy and radiotherapy over the past few decades. Prognosis can be most accurately predicted by genetic profiling of fine needle aspiration biopsy of the tumor before the treatment, and high-risk patients can now be identified for clinical trials that may lead to target-based therapies for metastatic disease and adjuvant therapy which aims to prevent metastatic disease.
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Project description:Background:High-risk non-muscle invasive bladder cancer (HR-NMIBC) is a clinically unpredictable disease. Despite clinical risk estimation tools, many patients are undertreated with intra-vesical therapies alone, whereas others may be over-treated with early radical surgery. Molecular biomarkers, particularly DNA methylation, have been reported as predictive of tumour/patient outcomes in numerous solid organ and haematologic malignancies; however, there are few reports in HR-NMIBC and none using genome-wide array assessment. We therefore sought to identify novel DNA methylation markers of HR-NMIBC clinical outcomes that might predict tumour behaviour at initial diagnosis and help guide patient management. Patients and methods:A total of 21 primary initial diagnosis HR-NMIBC tumours were analysed by Illumina HumanMethylation450 BeadChip arrays and subsequently bisulphite Pyrosequencing. In all, 7 had not recurred at 1?year after resection and 14 had recurred and/or progressed despite intra-vesical BCG. A further independent cohort of 32 HR-NMIBC tumours (17 no recurrence and 15 recurrence and/or progression despite BCG) were also assessed by bisulphite Pyrosequencing. Results:Array analyses identified 206 CpG loci that segregated non-recurrent HR-NMIBC tumours from clinically more aggressive recurrence/progression tumours. Hypermethylation of CpG cg11850659 and hypomethylation of CpG cg01149192 in combination predicted HR-NMIBC recurrence and/or progression within 1?year of diagnosis with 83% sensitivity, 79% specificity, and 83% positive and 79% negative predictive values. Conclusions:This is the first genome-wide DNA methylation analysis of a unique HR-NMIBC tumour cohort encompassing known 1-year clinical outcomes. Our analyses identified potential novel epigenetic markers that could help guide individual patient management in this clinically unpredictable disease.
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Project description:Approximately 15% of patients with prostate cancer are diagnosed with high-risk disease. However, the current definitions of high-risk prostate cancer include a heterogeneous group of patients with a range of prognoses. Some have the potential to progress to a lethal phenotype that can be fatal, while others can be cured with treatment of the primary tumour alone. The optimal management of this patient subgroup is evolving. A refined classification scheme is needed to enable the early and accurate identification of high-risk disease so that more-effective treatment paradigms can be developed. We discuss several principles established from clinical trials, and highlight other questions that remain unanswered. This Review critically evaluates the existing literature focused on defining the high-risk population, the management of patients with high-risk prostate cancer, and future directions to optimize care.
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