Purpose
Over the last decade, we have seen the emergence of tissue-based genomic prognostic markers that can be used for decision-making regarding the need for treatment. This review provides an ...up-to-date summary of the relevant literature surrounding these markers with a discussion of the relevant strength and limitations.
Methods
We performed a literature search of tissue-based genomic prognostic markers and selected those that were currently available for clinical use. We selected the following markers for further review: Decipher (Decipher Bioscience), Polaris (Myriad), Genome Prostate Score (Oncotype Dx), and Promark. We selected the initial validation study for each marker along with other validation studies in independent cohorts. Furthermore, we selected available clinical utility studies or studies combining multi parametric MRI.
Results
In this article, we provide an in-depth review of four commercially available biomarkers and discuss the current literature surrounding these markers, including the benefits and limitations of their use. We found that each of these markers has evidence supporting their role as an independent predictor of relevant prostate cancer endpoints, which can be helpful for clinical decision-making. However, issues related to heterogeneity and a lack of prospective randomized studies supporting their utility are limitations. Evidence appears to suggest that MRI and genomic risk assessment maybe complementary.
Conclusion
Although these markers can help in improved risk stratification of patients eligible for AS, more prospective studies with head to head comparison between markers are needed to elucidate the true potential of these markers in AS.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Background Few studies have reported on late declines and long-term health-related quality of life (HRQOL) after prostate cancer (PCa) treatment. Objective We assessed long-term HRQOL ...following various treatments for localized PCa. Design, setting, and participants This cohort study of HRQOL up to 10 yr after treatment used a prospectively accrued, nationwide PCa registry that collects longitudinal patient-reported HRQOL. Intervention Various primary treatments for localized PCa. Outcome measurements and statistical analysis The Medical Outcomes Studies 36-item Short Form and the University of California, Los Angeles, Prostate Cancer Index characterized physical function, mental health, and sexual, urinary, and bowel function and bother. Repeated measures mixed-model analysis assessed change in HRQOL by treatment over time, and logistic regression was used to measure the likelihood of a clinically significant decline in HRQOL. Results and limitations Among 3294 men, 1139 (34%) underwent nerve-sparing radical prostatectomy (NSRP), 860 (26%) underwent non-NSRP, 684 (21%) underwent brachytherapy, 386 (12%) underwent external beam radiotherapy, 161 (5%) underwent primary androgen deprivation therapy, and 64 (2%) pursued watchful waiting/active surveillance. Median follow-up was 74 mo (interquartile range: 50–102). Most treatments resulted in early declines in HRQOL, with some recovery over the next 1–2 yr and a plateau in scores thereafter. Surgery had the largest impact on sexual function and bother and on urinary function, radiation had the strongest effect on bowel function, and androgen deprivation therapy had the strongest effect on physical function. The main limitation was attrition among the cohort. Conclusions Although most men experience initial declines in HRQOL in the first 2 yr after treatment, there is little change from 3 to 10 yr and most differences between treatments attenuated over time. Patient summary Various treatments for prostate cancer result in a distinct constellation of adverse effects on health-related quality of life, which may have a long-term impact. These findings are helpful regarding shared decision making over choice of primary treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
To evaluate the performance of mpMRI and the 4Kscore test together for the detection of significant prostate cancer. Material and methods We selected a consecutive series of men who were referred for ...evaluation of prostate cancer at an academic institution and underwent mpMRI and the 4Kscore test. The primary outcome was the presence of Gleason 7 or higher cancer on biopsy of the prostate. We used logistic regression and Decision Curve Analysis to report the discrimination and clinical utility of using mpMRI and the 4Kscore test for prostate cancer detection. We modeled the probability of harboring a Gleason 7 or higher prostate cancer based on the 4Kscore test and mpMRI findings. Finally, we examined various combinations and sequences of mpMRI and the 4Kscore test and assessed the impact on biopsies avoided and cancers missed.
Among 300 men who underwent a 4Kscore test and mpMRI, 149 (49%) underwent a biopsy. Among those, 73 (49%) had cancer, and 49 (33%) had Gleason 7 cancer. The area under the curve (AUC) for using the 4Kscore test and mpMRI together 0.82 (0.75-0.89) was superior to using the 4Kscore 0.70 (0.62-0.79) or mpMRI 0.74 (0.66-0.81) individually (p = 0.001). Similarly, decision analysis revealed the highest net benefit was achieved using both tests.
The 4Kscore test and mpMRI results provide independent, but complementary, information that enhances the prediction of higher-grade prostate cancer and improves patient's selection for a prostate biopsy. Prospective trials are required to confirm these findings.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Context Despite excellent cancer control with the treatment of localized prostate cancer (PCa), some men will experience a recurrence of disease. The optimal management of recurrent disease ...remains uncertain. Objective To systematically review recent literature regarding management of biochemical recurrence after primary treatment for localized PCa. Evidence acquisition A comprehensive systematic review of the literature was performed from 2000 to 2012 to identify articles pertaining to management after recurrent PCa. Search terms included prostate cancer recurrence, salvage therapy, radiorecurrent prostate cancer, post HIFU, post cryoablation, postradiation , and postprostatectomy salvage. Studies were selected according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines and required to provide a comprehensive description of primary and secondary treatments along with outcomes. Evidence synthesis The data from 32 original publications were reviewed. The most common option for local salvage therapy after radical prostatectomy (RP) was radiation. Options for local salvage therapy after primary radiation included RP, brachytherapy, and cryotherapy. Different definitions of recurrence and risk profiles among patients make comparative assessment among salvage treatment modalities difficult. Triggers for intervention and factors predicting response to salvage therapy vary. Conclusions Radiation therapy (RT) after RP can provide durable prostate-specific antigen (PSA) responses in a sizeable percentage of men, especially when given early (ie, PSA <1 ng/ml). Though a few studies suggest improvements in mortality, prospective randomized trials are needed and underway. The role of salvage treatment after RT is less clear.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective
To compare survival outcome between chemoradiation therapy (CRT) and radical cystectomy (RC) for muscle‐invasive bladder cancer (MIBC).
Patients and Methods
We conducted a retrospective ...analysis of patients with MIBC (≥cT2, N0, M0) in the National Cancer Database (2004–2013). CRT was defined as a radiation dose of ≥40 Gy and chemotherapy within 90 days of radiation. Descriptive statistics were used to compare groups. RC and CRT patients were propensity matched. Kaplan–Meier analysis was used to compare overall survival (OS). Multivariable Cox regression was used to determine predictors of survival.
Results
In all, 8 379 (6 606 RC and 1 773 CRT) patients met the inclusion criteria and 1 683 patients in each group were propensity matched. On multivariable extended Cox analysis, significant predictors of decreased OS were age, Charlson‐Deyo Comorbidity score of 1, Charlson‐Deyo Comorbidity score of 2, stage cT3–4, and urothelial histology. CRT was associated with decreased mortality at year 1 (hazard ratio HR 0.84, 95% confidence interval CI 0.74–0.96; P = 0.01), but at 2 years (HR 1.4, 95% CI 1.2–1.6; P < 0.001) and 3 years onward (HR 1.5, 95% CI 1.2–1.8; P < 0.001) CRT was associated with increased mortality. The 5‐year OS was greater for RC than for CRT (38% vs 30%, P = 0.004).
Conclusions
Initially after treatment for MIBC the risk of mortality is lower with CRT compared to RC. However, at ≥2 years after treatment the mortality risk favours RC. Patients who are suitable surgical candidates, with a low risk of morbidity, may be better served by RC.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Abstract Background Decipher is a validated genomic classifier developed to determine the biological potential for metastasis after radical prostatectomy (RP). Objective To evaluate the ability of ...biopsy Decipher to predict metastasis and Prostate cancer-specific mortality (PCSM) in primarily intermediate- to high-risk patients treated with RP or radiation therapy (RT). Design, setting, and participants Two hundred and thirty-five patients treated with either RP ( n = 105) or RT ± androgen deprivation therapy ( n = 130) with available genomic expression profiles generated from diagnostic biopsy specimens from seven tertiary referral centers. The highest-grade core was sampled and Decipher was calculated based on a locked random forest model. Outcome measurements and statistical analysis Metastasis and PCSM were the primary and secondary outcomes of the study, respectively. Cox analysis and c-index were used to evaluate the performance of Decipher. Results and limitations With a median follow-up of 6 yr among censored patients, 34 patients developed metastases and 11 died of prostate cancer. On multivariable analysis, biopsy Decipher remained a significant predictor of metastasis (hazard ratio: 1.37 per 10% increase in score, 95% confidence interval CI: 1.06–1.78, p = 0.018) after adjusting for clinical variables. For predicting metastasis 5-yr post-biopsy, Cancer of the Prostate Risk Assessment score had a c-index of 0.60 (95% CI: 0.50–0.69), while Cancer of the Prostate Risk Assessment plus biopsy Decipher had a c-index of 0.71 (95% CI: 0.60–0.82). National Comprehensive Cancer Network risk group had a c-index of 0.66 (95% CI: 0.53–0.77), while National Comprehensive Cancer Network plus biopsy Decipher had a c-index of 0.74 (95% CI: 0.66–0.82). Biopsy Decipher was a significant predictor of PCSM (hazard ratio: 1.57 per 10% increase in score, 95% CI: 1.03–2.48, p = 0.037), with a 5-yr PCSM rate of 0%, 0%, and 9.4% for Decipher low, intermediate, and high, respectively. Conclusions Biopsy Decipher predicted metastasis and PCSM from diagnostic biopsy specimens of primarily intermediate- and high-risk men treated with first-line RT or RP. Patient summary Biopsy Decipher predicted metastasis and prostate cancer-specific mortality risk from diagnostic biopsy specimens.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The potential association between androgen deprivation therapy (ADT) and cardiovascular mortality (CVM) remains controversial. This study assessed mortality outcomes in a large national registry to ...further elucidate the association between treatment selection and cause of mortality.
A total of 7,248 men in the CaPSURE registry were analyzed. Treatment was categorized as local only, primary ADT monotherapy, local treatment plus ADT, and watchful waiting/active surveillance (WW/AS). Competing hazards survival analysis was performed for prostate cancer-specific mortality (PCSM), CVM, and all-cause mortality. A propensity score-adjusted and a propensity-matched analysis were undertaken to adjust for imbalances in covariates among men receiving various treatments.
Patients treated with ADT or WW/AS had a higher likelihood of PCSM than those treated with local therapy alone. Patients treated with primary ADT had an almost two-fold greater likelihood of CVM (HR, 1.94; 95% CI, 1.29 to 2.97) than those treated with local therapy alone; however, patients treated with WW/AS had a greater than two-fold increased risk of CVM (HR, 2.46; 95% CI, 1.53 to 3.95). A propensity-matching algorithm in a subset of 1,391 patients was unable to find a significant difference in CVM between those who did or did not receive ADT.
Patients matched on propensity to receive ADT did not show an association between ADT and CVM. This suggests that potential unmeasured variables affecting treatment selection may confound the relationship between ADT use and cardiovascular risk. However, an association may yet exist, because the propensity score could not include all known risk factors for CVM.
An observed decrease of physician scientists in medical practice has generated much recent interest in increasing the exposure of research programs in medical school. The aim of this study was to ...review the experience and attitudes regarding research by medical students in Canada.
An anonymous, cross-sectional, self-report questionnaire was administered to second and fourth year students in three medical schools in Ontario between February and May of 2005. Questions were primarily closed-ended and consisted of Likert scales. Descriptive and correlative statistics were used to analyze the responses between students of different years and previous research experience.
There was a 47% (327/699) overall response rate to the questionnaire. Despite 87% of respondents reporting that they had been involved in some degree of research prior to medical school, 43% report that they have not been significantly involved in research activity during medical school and 24% had no interest in any participation. There were significant differences in the attitudes towards research endeavors during medical school between students in their fourth year compared to second year. The greatest barriers to involvement in research in medical school appear to be time, availability of research mentors, formal teaching of research methodology and the perception that the student would not receive appropriate acknowledgement for work put towards a research project.
The results of this self-report survey outline the significant differences in attitudes towards mandatory research as a component of critical inquiry and scholarship in the undergraduate curriculum in Ontario medical schools.
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