Is moderate hypofractionation accepted as a new standard of care in north america for prostate cancer patients treated with external beam radiotherapy? Survey of genitourinary expert radiation oncologists

INTRODUCTION: Several recent randomized clinical trials have evaluated hypofractionated regimens against conventionally fractionated EBRT and shown similar effectiveness with conflicting toxicity results. The current view regarding hypofractionation compared to conventional EBRT among North American genitourinary experts for management of prostate cancer has not been investigated. MATERIALS AND METHODS: A survey was distributed to 88 practicing North American GU physicians serving on decision - making committees of cooperative group research organizations. Questions pertained to opinions regarding the default EBRT dose and fractionation for a hypothetical example of a favorable intermediate - risk prostate cancer (Gleason 3 + 4). Treatment recommendations were correlated with practice patterns using Fisher's exact test. RESULTS: Forty - two respondents (48%) completed the survey. We excluded from analysis two respondents who selected radical hypofractionation with 5 - 12 fractions as a preferred treatment modality. Among the 40 analyzed respondents, 23 (57.5%) recommend conventional fractionation and 17 (42.5%) recommended moderate hypofractionation. No demographic factors were found to be associated with preference for a fractionation regimen. Support for brachytherapy as a first choice treatment modality for low - risk prostate cancer was borderline significantly associated with support for moderate hypofractionated EBRT treatment modality (p = 0.089). CONCLUSIONS: There is an almost equal split among North American GU expert radiation oncologists regarding the appropriateness to consider moderately hypofractionated EBRT as a new standard of care in management of patients with prostate cancer. Physicians who embrace brachytherapy may be more inclined to support moderate hypofractionated regimen for EBRT. It is unclear whether reports with longer followups will impact this balance, or whether national care and reimbursement policies will drive the clinical decisions. In the day and age of patient - centered care delivery, patients should receive an objective recommendation based on available clinical evidence. The stark division among GU experts may influence the design of future clinical trials utilizing EBRT for patients with prostate cancer

Is lymphovascular invasion a powerful predictor for biochemical recurrence in pT3 N0 prostate cancer?: Results from the K-CaP database

To assess the impact of lymphovascular invasion (LVI) on the risk of biochemical recurrence (BCR) in pT3 N0 prostate cancer, clinical data were extracted from 1,622 patients with pT3 N0 prostate cancer from the K-CaP database. Patients with neoadjuvant androgen deprivation therapy (n = 325) or insufficient pathologic or follow-up data (n = 87) were excluded. The primary endpoint was the oncologic importance of LVI, and the secondary endpoint was the hierarchical relationships for estimating BCR between the evaluated variables. LVI was noted in 260 patients (21.5%) and was significantly associated with other adverse clinicopathologic features. In the multivariate Cox regression analysis, LVI was significantly associated with an increased risk of BCR after adjusting for known prognostic factors. In the Bayesian belief network analysis, LVI and pathologic Gleason score were found to be first-degree associates of BCR, whereas prostate-specific antigen (PSA) level, seminal vesicle invasion, perineural invasion, and high-grade prostatic intraepithelial neoplasia were considered second-degree associates. In the random survival forest, pathologic Gleason score, LVI, and PSA level were three most important variables in determining BCR of patients with pT3 N0 prostate cancer. In conclusion, LVI is one of the most powerful adverse prognostic factors for BCR in patients with pT3 N0 prostate cancer.1132Ysciescopu

Active surveillance - Is it feasible for intermediate-risk localised prostate cancer?

Background Although active surveillance (AS) is a well-recognised treatment option for localised low-risk prostate cancer (LRPC), its role in the management of localised intermediate-risk prostate cancer (IRPC) is not clear yet and the available literature is slightly contradictory. Objective To compare the outcome of AS between LRPC and IRPC patients. Design, setting, and participants Between November 2002 and August 2019, 372 men with localised prostate cancer (PC) underwent AS in our hospital based on local departmental protocol. Outcome measurements and statistical analysis The primary outcome measures were overall survival, disease progression–free survival, treatment-free survival, and biochemical recurrence–free survival. Survival times in the low- and intermediate-risk groups were compared using Cox regression analysis. Results and limitations Out of 372 localised PC patients, 276 (74%) had LRPC and 96 (26%) IRPC. Overall, 86 (31.2%) low-risk and 25 (26%) intermediate-risk patients developed disease progression, and 86 (31.2%) low-risk and 22 (23%) intermediate-risk patients underwent active treatment. Among the treated patients, eight (2.9%) LRPC patients and one (1%) IRPC patient developed biochemical recurrence. In total, only one patient (from the low-risk group) had metastasis and 25 patients passed away (18 from the low-risk and seven from the intermediate-risk group). No death was recorded due to PC in the cohort. There was no difference in any of the survival outcomes between LRPC and IRPC patients in unadjusted analysis as well as when analysis was performed after adjusting the potentially confounding factors. Limitations include relatively short median follow-up time and failure to objectively define the criteria for the selection of IRPC patients suitable for AS. Conclusions The option of AS could be considered for carefully selected and well-informed patients with IRPC provided close structured monitoring is maintained. Patient summary In this report, we looked at various survival outcomes of active surveillance between low- and intermediate-risk prostate cancer patients in a large British population. There was no difference in any of the survival outcomes between the two groups. We concluded that carefully selected intermediate-risk prostate cancer patients could be offed the option of active surveillance

Expression of the TMPRSS2:ERG fusion gene predicts cancer recurrence after surgery for localised prostate cancer

The prostate-specific gene, TMPRSS2 is fused with the gene for the transcription factor ERG in a large proportion of human prostate cancers. The prognostic significance of the presence of the TMPRSS2:ERG gene fusion product remains controversial. We examined prostate cancer specimens from 165 patients who underwent surgery for clinically localised prostate cancer between 1998 and 2006. We tested for the presence of TMPRSS2:ERG gene fusion product, using RT–PCR and direct sequencing. We conducted a survival analysis to determine the prognostic significance of the presence of the TMPRSS2:ERG fusion gene on the risk of prostate cancer recurrence, adjusting for the established prognostic factors. We discovered that the fusion gene was expressed within the prostate cancer cells in 81 of 165 (49.1%) patients. Of the 165 patients, 43 (26.1%) developed prostate-specific antigen (PSA) relapse after a mean follow-up of 28 months. The subgroup of patients with the fusion protein had a significantly higher risk of recurrence (58.4% at 5 years) than did patients who lacked the fusion protein (8.1%, P<0.0001). In a multivariable analysis, the presence of gene fusion was the single most important prognostic factor; the adjusted hazard ratio for disease recurrence for patients with the fusion protein was 8.6 (95% CI=3.6–20.6, P<0.0001) compared to patients without the fusion protein. Among prostate cancer patients treated with surgery, the expression of TMPRSS2:ERG fusion gene is a strong prognostic factor and is independent of grade, stage and PSA level

Genomic Classifier Augments the Role of Pathological Features in Identifying Optimal Candidates for Adjuvant Radiation Therapy in Patients With Prostate Cancer: Development and Internal Validation of a Multivariable Prognostic Model.

Purpose Despite documented oncologic benefit, use of postoperative adjuvant radiotherapy (aRT) in patients with prostate cancer is still limited in the United States. We aimed to develop and internally validate a risk-stratification tool incorporating the Decipher score, along with routinely available clinicopathologic features, to identify patients who would benefit the most from aRT. Patient and Methods Our cohort included 512 patients with prostate cancer treated with radical prostatectomy at one of four US academic centers between 1990 and 2010. All patients had ≥ pT3a disease, positive surgical margins, and/or pathologic lymph node invasion. Multivariable Cox regression analysis tested the relationship between available predictors (including Decipher score) and clinical recurrence (CR), which were then used to develop a novel risk-stratification tool. Our study adhered to the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines for development of prognostic models. Results Overall, 21.9% of patients received aRT. Median follow-up in censored patients was 8.3 years. The 10-year CR rate was 4.9% vs. 17.4% in patients treated with aRT versus initial observation ( P \u3c .001). Pathologic T3b/T4 stage, Gleason score 8-10, lymph node invasion, and Decipher score \u3e 0.6 were independent predictors of CR (all P \u3c .01). The cumulative number of risk factors was 0, 1, 2, and 3 to 4 in 46.5%, 28.9%, 17.2%, and 7.4% of patients, respectively. aRT was associated with decreased CR rate in patients with two or more risk factors (10-year CR rate 10.1% in aRT v 42.1% in initial observation; P = .012), but not in those with fewer than two risk factors ( P = .18). Conclusion Using the new model to indicate aRT might reduce overtreatment, decrease unnecessary adverse effects, and reduce risk of CR in the subset of patients (approximately 25% of all patients with aggressive pathologic disease in our cohort) who benefit from this therapy

Prevalence and factors associated to incidental prostate carcinoma among patients undergoing turp for benign prostatic enlargement.

Background: Prostate carcinoma carries higher morbidity and mortality when diagnosed late. Prostate cancer screening is paramount, however, there are no specific clinical signs for early-stage prostate cancer. As an independent variable, prostate-specific antigen is an established predictor of cancer. Incidental prostate cancer is detected by histological examination of resected biopsy tissue that had been previously diagnosed as benign. In the current PSA-use era the prevalence of incidental prostate cancer ranges from 1.4 to 13%. The prevalence in Tanzania as published by Gunda et al was 21.71%. This is alarmingly high. However, in his study, patients with high prostate-specific antigens were included. Objective: To determine the prevalence of incidental prostate carcinoma among patients undergoing transurethral resection of the prostate for benign prostate enlargement with prostate-specific antigen less than 5.5 ng/ml. Methods: A retrospective hospital-based cross-sectional study was conducted to establish the prevalence of incidental prostate cancer among men who underwent transurethral resection of the prostate with a considered normal range of prostate-specific antigen from 2010 to 2019 in Dar es Salaam, Tanzania. A minimum of 195 participants were reviewed, and factors associated with incidental prostate carcinoma were evaluated by binary regression analysis. Results: A total of 195 men were included in the study. The prevalence of incidental prostate cancer among men with prostate-specific antigen levels of less than 5.5ng/mL was 7.2%. More than half of the patients had high-grade cancer, and three quarters had T1b histological subtype making up the clinically significant category. For every one year increase in age from 76 years, v the risk of incidental prostate cancer increased by 1.6, and for every unit increase in prostate specific antigen, incidental prostate cancer increased by 2.2. Conclusion: The Incidental prostate cancer detection rate of 7.2% in our settings is within the Internationals range. Factors associated, were prostate-specific antigen levels and Age. 3.6% of all patient had high grade cancer with potential chance of progressing to an advance stage of prostate cance

Re-stratification of Patients with High-Risk Prostate Cancer According to the NCCN Guidelines among Patients Who Underwent Radical Prostatectomy: An Analysis Based on the K-CaP Registry

PURPOSE: The present study aimed to re-stratify patients with high-risk prostate cancer according to the National Comprehensive Cancer Network guidelines among patients who underwent radical prostatectomy (RP). MATERIALS AND METHODS: This study used the Korean Prostate Cancer Database registry and identified 1,060 patients with high-risk prostate cancer who underwent RP between May 2001 and April 2013. All patients were categorized into risk groups, and subgroups were identified according to the type and number of high-risk factors. RESULTS: Of the 1,060 high-risk patients, 599 (56.5%), 408 (38.5%), and 53 (5.0%) had 1, 2, and 3 risk factors, respectively. In multivariate analysis, the Gleason score, percentage of positive biopsy cores, and number of risk factors present were identified as independent predictors of biochemical recurrence. There were significant differences in the 5-year postoperative biochemical failure-free survival (BCFFS) rate among the different high-risk factor subgroups (log-rank p 20 ng/mL alone and the intermediate-risk group with all factors (log-rank p=0.919 and p=0.781, respectively). Additionally, no significant difference was noted in the BCFFS rate between high-risk patients having all factors and those in the very-high-risk group (p=0.566). CONCLUSION: We successfully re-stratified patients with high-risk prostate cancer and identified the combinations of high-risk criteria that will help in the selection of patients for RP.ope

Prognostic Factors for Overall Survival and Risk Stratification of Prostate Cancer Patients with Biochemical Failure

Purpose: This study aims to determine prognostic factors for overall survival (OS) after biochemical failure (BF), and identify a risk stratification system to predict OS for prostate cancer patients with BF. Methods: Univariable and multivariable Cox proportional hazards regression analyses, and recursive partitioning analysis (RPA) were conducted using data from 1246 patients who experienced BF in the Genitourinary Radiation Oncologists of Canada (GUROC) Prostate Cancer Risk Stratification (ProCaRS) database. Two thirds of patients were randomized into a Training cohort (n=831), and the final third into a Validating cohort (n=415). Results: Age, baseline PSA, T stage, Gleason score, hormone therapy, radiation therapy, nadir PSA, TTBF and pre-BF PSADT were significant (p Conclusions: The 2-class post-treatment risk stratification system allows for the identification of high risk and low risk patients in terms of OS after BF to help guide patient selection for future clinical trials and clinical treatment decision-making

Tea and lycopene protect against prostate cancer

Prostate cancer is the most common male cancer in developed countries and is increasing in the developing world. Its long latency and geographical variation suggest the possibility of prevention or postponement of onset by dietary modification. To investigate the possible joint effect of lycopene and green tea on prostate cancer risk, a case-control study was conducted in Hangzhou, China, with 130 prostate cancer patients and 274 hospital controls. Information on tea and dietary intakes, and possible confounders was collected using a structured questionnaire. The risk of prostate cancer for the intake of tea and lycopene and their joint effect were assessed using multivariate logistic regression models. Prostate cancer risk was reduced with increased consumption of green tea. The protective effect of green tea was significant (odds ratio 0.14, 95% CI: 0.06-0.35) for the highest quartile relative to the lowest after adjusting for total vegetables and fruits intakes and other potential confounding factors. Intakes of vegetables and fruits rich in lycopene were also inversely associated with prostate cancer risk (odds ratio 0.18, 95% CI 0.08-0.39). Interaction analysis showed that the protective effect from tea and lycopene consumption was synergistic (p<0.01). This study suggests that habitual drinking tea and intakes of vegetables and fruits rich in lycopene could lead to a reduced risk of prostate cancer in Chinese men.Together they have a stronger preventive effect than either component taken separately. This is the first epidemiological study to investigate the joint effect between tea drinking and lycopene intake

Meta-analysis: Racial Disparities in Prostate Cancer Survival and Case-Control Study: Association between Family History of Cancers, Obesity and Prostate Cancer

This is a compilation of 3 abstracts for the three manuscripts included in this dissertation. I. Meta-Analysis: Racial Disparities in Prostate Cancer Survival: Prostate cancer is the second leading cause of cancer-related mortality in men. Previous studies have drawn inconsistent conclusions on racial differences in prostate cancer survival. This meta-analysis was conducted to investigate the relationship between race and survival from prostate cancer. A systematic review of published articles from 1968 to 2007 assessing survival from prostate cancer among African American and White men was conducted. The search yielded 20 eligible published manuscripts. Analysis of unadjusted studies showed African American men have an increased risk of all-cause mortality (Hazard ratio (HR) = 1.47, 95% confidence interval (CI): 1.31, 1.65, P \u3c 0.001). However, examination of adjusted studies showed no difference (HR = 1.07, 95% CI: 0.94, 1.22, P = 0.308). No statistically significant difference was observed in prostate cancer-specific survival in both analyses using unadjusted (HR = 1.11, 95% CI: 0.94, 1.31, P = 0.209) and adjusted studies (HR = 1.15, 95% CI: 0.95, 1.41, P = 0.157). There was evidence of heterogeneity that was unexplained by factors analyzed in overall survival but explained by stage in prostate cancer-specific survival. This meta-analysis concludes that there are no racial differences in the overall and prostate cancer-specific survival between African American and White men. II. Case-Control study: Association between Family History of Cancers and Prostate Cancer: Family history of prostate cancer is an established risk factor for prostate cancer. However, the relationship between family history of cancers other than prostate cancer and prostate cancer risk is inconclusive. This study sought to examine the association between family history of cancers and prostate cancer. A case-control study was conducted in which cases and controls were randomly selected from a large urology clinic in Central Virginia. Cases were 600 histologically confirmed prostate cancer patients who were diagnosed between January 2000 and December 2005, and controls were 686 patients who visited the clinic during the same period and diagnosed with urological illnesses other than cancers and prostate-related problems. Data on family history of cancers, lifestyle and demographic factors were collected. Unconditional logistic regression analysis was used to estimate the odds ratios and the corresponding 95% confidence intervals after adjustment for potential confounding factors. Multiple comparisons adjustments were made using Bonferroni adjustment. Men with family history of any cancer in first-degree relatives including parents (OR=2.42, 95% CI: 1.53, 3.84) and parents only (OR=1.90, 95% CI: 1.23, 2.94) were at increased risk of developing prostate cancer compared to men with no such family history of cancer. Significant increased risk was also observed with family history of prostate cancer in first-degree relatives (OR=2.68, 95% CI: 1.53, 4.69) and parents only (OR=3.26, 95% CI: 1.71, 6.24) compared to men with no family history of prostate cancer. Even after adjustments for multiple comparisons, the significance persisted both in first-degree relatives (OR=2.68, 95% CI: 1.16, 6.21) and parents alone (OR=3.26, 95% CI: 1.24, 8.63). No association was found with family history of other cancers including breast, colon, lung, skin, digestive tract, stomach, liver, pancreas, female cancers, urogenital, urinary bladder, brain, blood and lymph node and other cancers and risk of prostate cancer. This study demonstrated an increased prostate cancer risk for men with a family history of any cancer or prostate cancer in first-degree relatives including parents and parents alone. Health care providers need to be aware of the potential risk of family history of cancers on prostate cancer. III. Case-Control study: Association between Obesity and Prostate Cancer: Obesity is a major public health problem in the United States. Several studies have investigated the association between obesity and prostate cancer risk. However the impact of early-adult obesity on prostate cancer is not well studied. This study proposes to investigate the relationship between prostate cancer and early-onset obesity and current obesity. A case-control study was conducted to investigate the relationship between obesity and prostate cancer in a large urology clinic population in Central Virginia. Cases included histologically confirmed prostate cancer patients of all stages and grades diagnosed from January 2000 to December 2005. Controls were patients who were diagnosed with urological illness other than cancers and prostate-related problems. Self-reported data was collected on anthropometric, lifestyle and demographic factors through a mail survey. Unconditional logistic regression analysis was conducted to investigate the association between prostate cancer and early-onset obesity (BMI at age 18) and current obesity. Odds ratios and corresponding 95% confidence intervals were calculated after accounting for significant interaction terms and adjusting for potential confounding variables. This study showed statistically significant association between BMI at age 18 and prostate cancer risk in the multivariate analysis when BMI was evaluated as a continuous variable. There was a 7% decrease in the odds of prostate cancer risk for every 1 kg/m(2) increment in BMI at age 18 (OR=0.93, 95% CI: 0.87, 0.98). Analysis of BMI at age 18 as a categorical variable also showed reduced risk though statistically non-significant. Obese men (OR=0.62, 95% CI: 0.12, 3.08) and overweight men (OR=0.60, 95% CI: 0.35, 1.05) had a non-significant decreased risk of developing prostate cancer compared to normal weight men at age 18. Examination of current BMI showed a non-statistically significant decreased risk of prostate cancer when examined as a continuous variable. However, there was significant interaction between current BMI treated categorically and age. This study concludes that there is decreased prostate cancer risk associated with increasing BMI at age 18. Future large prospective studies are needed to better understand the association between early-onset obesity and risk of prostate cancer and explore the biological factors associated especially in the early ages. This document was created in Microsoft Word 2003