Secondary analysis of late major gastrointestinal and genitourinary toxicities in unfavorable-risk prostate cancer patients receiving docetaxel: Insights from a randomized trial.

BACKGROUND: This study sought to evaluate the late toxicity associated with neoadjuvant and concurrent docetaxel and radiation therapy in patients with prostate cancer. METHODS: A secondary analysis was performed of the phase 3 multicenter randomized trial (Dana-Farber Cancer Institute 05-043) including 350 patients with nonmetastatic unfavorable-risk prostate cancer. Patients were randomized 1:1 to receive androgen deprivation therapy, radiation therapy, and docetaxel versus androgen deprivation therapy and radiation therapy. The study assessed the cumulative incidence rates of grade 2 and grade 3 or higher gastrointestinal, genitourinary, and sexual toxicity. A multivariable Fine and Gray's competing risks regression model adjusted for age at randomization and pelvic lymph node radiation therapy was used to evaluate the treatment effect of docetaxel on time to late genitourinary and gastrointestinal toxicities. RESULTS: The study included 338 patients who primarily had minimal or no comorbidity (74.9%) and median age 66 years (interquartile range: 61,71). At a median follow-up of 10.2 years, docetaxel was not associated with increased risk of any grade 3 or higher (adjusted hazard ratio [AHR], 0.98; 95% confidence interval [CI], 0.36-2.67; p = .96) or grade 2 gastrointestinal (p = .75), genitourinary (p = .44), and sexual (p = .29) toxicity. Age was associated with increased grade 3 or higher (AHR, 1.08; 95% CI, 1.01-1.16; p = .03) and grade 2 gastrointestinal toxicity (AHR, 1.11; 95% CI, 1.03-1.20; p = .005). A nonsignificant trend (p = .09) toward increased late grade 3 or higher toxicity was observed for pelvic radiation therapy use. CONCLUSIONS: Docetaxel combined with radiotherapy has an acceptable long-term toxicity profile.

Prostate cancer presentation and management in the Middle East.

BACKGROUND: Although prostate cancer is a prevalent malignancy worldwide, its clinical presentation and management in the Middle East are not well-documented. This study aims to provide insights into the initial clinical presentation and management of prostate cancer in this region. METHODS: A retrospective review was conducted on seven institutional databases from six Middle Eastern countries, including Türkiye, Lebanon, Iraq, Syria, Bahrain, and Jordan, to identify patients diagnosed with prostate cancer in 2021. Descriptive analysis was performed on the collected data to provide an overview of the demographic, clinical, and treatment variables. RESULTS: A total of 1,136 patients were identified with a median age of 70 (range, 50-84). Most patients (78%) received their prostate cancer diagnosis after presenting with symptoms, as opposed to routine PSA screening. At the time of diagnosis, 35% of men had clinical T3 or T4 disease, 54% with Stage IV disease and 50% with Gleason score ≥ 8. Regarding treatment, 20% of non-metastatic and 22% of metastatic patients received no treatment. CONCLUSION: Most men in this study sought prostate cancer evaluation due to symptoms and were subsequently diagnosed with advanced-stage disease, providing a foundation for future research aimed at understanding the underlying factors behind the observed trends and enabling informed interventions.

Race- and Age-Related Disparities in Cervical Cancer Mortality.

BACKGROUND: Although the incidence of cervical cancer among younger Black women is now equivalent to that of White women, it is unknown whether the reduced incidence has affected survival rates among younger Black women. The goal of this study was to assess differences in survival by age and race. PATIENTS AND METHODS: A retrospective cohort study was performed using the National Cancer Database to analyze women with nonmetastatic cervical cancer diagnosed between 2004 and 2014. Women with unknown survival data and those who died within 3 months of diagnosis were excluded. Multivariable logistic regression models evaluated interactions between age and race (Black vs non-Black) for presentation with stage I disease and receipt of optimal treatment. A multivariable Cox regression model was used to evaluate survival differences by age and race. RESULTS: Of 55,659 women included, 16.4% were Black. Compared with their non-Black counterparts, fewer Black women presented with stage I disease (37.8% vs 47.8%; P<.01) and received optimal treatment (46.2% vs 58.3%; P<.01). Fewer Black women had private insurance if they were aged <65 years (39.6% vs 55.7%; P<.01), but not if they were aged ≥65 years (11.7% vs 12.4%; P=.43). According to multivariable logistic regression, Black women aged ≤39 years were less likely to present with stage I disease, with a significant interaction term between age and race (P<.01 for interaction). Disparities in overall survival by race were greatest for Black women aged ≤39 years (adjusted hazard ratio, 1.32; 95% CI, 1.20-1.46; P<.01) but decreased with increasing age interval until no disparity was noted for women aged ≥65 years (P<.01 for interaction). CONCLUSIONS: Younger Black women with cervical cancer are at risk for presenting with higher-stage disease and having worse overall survival. These findings may be related to insurance-related disparities and inadequate follow-up for abnormal Papanicolaou test results. Younger Black women with cervical cancer may be a particularly vulnerable population.

Patterns of care and predictors of adjuvant radiation therapy in phyllodes tumor of the breast.

Patterns of care, utilization, and predictors of adjuvant radiation therapy (RT) for phyllodes tumors of the breast were retrospectively analyzed using the National Cancer Database. We identified 3080 patients; 53.4% received lumpectomy and 35.9% mastectomy. 25.9% of patients had lymph node sampling or dissection. 23.2% received adjuvant RT, which doubled in utilization over a decade. Predictors of RT were younger age, fewer comorbidities, less favorable pathologic features, and treatment at academic centers. There was no association between RT and overall survival (AHR 1.21, 95% CI 0.97-1.53, P = .097). Despite national guidelines recommending against nodal sampling or RT, it remains prevalent. Further research on indications for adjuvant radiation for phyllodes is needed.

Combined External Beam Radiation Therapy and Brachytherapy versus Radical Prostatectomy with Adjuvant Radiation Therapy for Gleason 9-10 Prostate Cancer.

PURPOSE: It remains controversial whether external beam radiation therapy with a brachytherapy boost provides oncologic outcomes equivalent to those of radical prostatectomy with or without adjuvant radiation therapy in men with Gleason 9-10 prostate cancer. We compared external beam radiation therapy plus brachytherapy to radical prostatectomy plus adjuvant radiation therapy for Gleason 9-10 prostate cancer in terms of overall survival and prostate cancer specific mortality in 2 large national databases. MATERIALS AND METHODS: Using the NCDB (National Cancer Database) and the SEER (Surveillance, Epidemiology, and End Results) database, we identified 4,367 and 2,276 patients, respectively, diagnosed with clinical T1-T3N0M0, Gleason 9-10, prostate specific antigen 0 to 40 ng/ml prostate cancer treated with external beam radiation therapy plus brachytherapy or radical prostatectomy plus adjuvant radiation therapy. We compared overall survival and prostate cancer specific mortality using inverse probability of treatment weighted multivariable Cox proportional hazards regression modeling after accounting for clinical and demographic factors. RESULTS: Median followup in the NCDB and SEER cohorts was 6.0 years and 5.8 years, respectively. In the NCDB cohort there was no significant difference in 5-year overall survival between radical prostatectomy plus adjuvant radiation therapy vs external beam radiation therapy plus brachytherapy (86.7% vs 87.0%, AHR 1.10, 95% CI 0.95-1.27, p=0.220). Results were unchanged when including only patients who received androgen deprivation therapy. In the SEER cohort there was no difference in 5-year prostate cancer specific mortality (6.0% vs 5.7%, AHR 1.22, 95% CI 0.0.88-1.71, p=0.234). There was no significant interaction between patient age (65 years or greater vs less than 65) and treatment modality in the NCDB or SEER cohorts. CONCLUSIONS: In men with Gleason 9-10 prostate cancer multimodality surgical therapy is equivalent to external beam radiation therapy plus brachytherapy.

Racial disparities in brachytherapy administration and survival in women with locally advanced cervical cancer.

OBJECTIVE: Black women have the highest incidence and mortality from cervical cancer in the United States. This study evaluated whether racial disparities in the receipt of brachytherapy (BT) for locally advanced cervical cancer mediate survival differences by race using the National Cancer Database. METHODS: A retrospective cohort study was performed using 16,116 women with stage IB2-IVA cervical cancer treated from 2004 to 2014. Women who did not receive external beam radiation therapy, those with unknown survival data or stage, and those status post hysterectomy or pelvic exenteration were excluded. Multivariate logistic regression was performed to evaluate factors associated with BT use. Using a propensity score adjusted model with inverse probability treatment weighting, adjusted hazard ratios for overall survival were calculated, including an interaction term between BT and race. RESULTS: Of 16,116 patients, 19.2% were black and 55.8% received BT. Black women were significantly less likely to receive BT (AOR 0.87, 95% confidence interval [CI] 0.79-0.96, p = 0.007) and had worse all-cause mortality (median survival 3.9 years [95% CI 3.6-4.6] versus 5.2 years [95% CI 4.9-5.5] for non-black women, p < 0.001). In the adjusted model, black patients had an increased risk of death compared to non-black patients (AHR 1.14, 95% CI 1.05-1.24; p = 0.002) among women who did not receive BT. However, there was no difference in survival by race when both groups received BT (AHR 1.04, 95% CI 0.95-1.13, p = 0.42; p-interaction = 0.005). CONCLUSIONS: Black women with locally advanced cervical cancer are less likely to receive brachytherapy, which mediates survival differences by race. Improving access to brachytherapy may improve overall survival.

Practice Patterns and Outcomes Among Patients With N0M0 Prostate Cancer and a Very High Prostate-Specific Antigen Level.

BACKGROUND: Management of patients with a very high prostate-specific antigen (PSA) level (≥98.0 ng/mL) but clinically localized (N0M0) prostate cancer is challenging. This study sought to determine practice patterns and outcomes among these patients. PATIENTS AND METHODS: A total of 748,825 patients with prostate cancer from 2004 through 2012 were identified using the National Cancer Database. These patients were subdivided by PSA level (0-9.9, 10.0-19.9, 20.0-39.9, 40.0-59.9, 60.0-79.9, 80.0-97.9, and ≥98.0 ng/mL), nodal status (N0 vs N1), and distant metastases (M0 vs M1). Rates of locoregional treatment and 5-year overall survival (OS) in each group were determined. Survival was compared using Cox regression after adjusting for multiple patient-specific factors. RESULTS: The rate of locoregional treatment for patients with N0M0 disease and PSA level ≥98.0 ng/mL was significantly lower than for those with N1M0 disease (52.6% vs 60.4%; P<.001) or N0M0 disease and PSA level <98.0 ng/mL (52.6% vs 86.6%; P<.001). The 5-year OS rate was similar for patients with N1M0 disease and those with N0M0 disease and a very high PSA level (63.2% vs 59.1%; adjusted hazard ratio [aHR], 0.91; P=.063). The survival benefit associated with locoregional treatment was higher among those with N0M0 disease and a very high PSA level than among those with N1M0 disease (aHR, 0.28 vs 0.44; P<.001). CONCLUSIONS: Patients with clinical N0M0 disease and a very high PSA level (≥98.0 ng/mL) have outcomes similar to those with N1 disease but receive locoregional treatment at a lower rate. Future work is needed to investigate the utility of locoregional treatment in this population.

Long-term outcomes of partial prostate treatment with magnetic resonance imaging-guided brachytherapy for patients with favorable-risk prostate cancer.

BACKGROUND: Partial prostate treatment has emerged as a potential method for treating patients with favorable-risk prostate cancer while minimizing toxicity. The authors previously demonstrated poor rates of biochemical disease control for patients with National Comprehensive Cancer Network (NCCN) intermediate-risk disease using partial gland treatment with brachytherapy. The objective of the current study was to estimate the rates of distant metastasis and prostate cancer-specific mortality (PCSM) for this cohort. METHODS: Between 1997 and 2007, a total of 354 men with clinical T1c disease, a prostate-specific antigen (PSA) level < 15 ng/mL, and Gleason grade ≤3 + 4 prostate cancer underwent partial prostate treatment with brachytherapy to the peripheral zone under 0.5-Tesla magnetic resonance guidance. The cumulative incidences of metastasis and PCSM for the NCCN very low-risk, low-risk, and intermediate-risk groups were estimated. Fine and Gray competing risk regression was used to evaluate clinical factors associated with time to metastasis. RESULTS: A total of 22 patients developed metastases at a median of 11.0 years (interquartile range, 6.9-13.9 years). The 12-year metastasis rates for patients with very low-risk, low-risk, and intermediate-risk disease were 0.8% (95% confidence interval [95% CI], 0.1%-4.4%), 8.7% (95% CI, 3.4%-17.2%), and 15.7% (95% CI, 5.7%-30.2%), respectively, and the 12-year PCSM estimates were 1.6% (95% CI, 0.1%-7.6%), 1.4% (95% CI, 0.1%-6.8%), and 8.2% (95% CI, 1.9%-20.7%), respectively. On multivariate analysis, NCCN risk category (low risk: hazard ratio, 6.34 [95% CI, 1.18-34.06; P = .03] and intermediate risk: hazard ratio, 6.98 [95% CI, 1.23-39.73; P = .03]) was found to be significantly associated with the time to metastasis. CONCLUSIONS: Partial prostate treatment with brachytherapy may be associated with higher rates of distant metastasis and PCSM for patients with intermediate-risk disease after long-term follow-up. Treatment of less than the full gland may not be appropriate for this cohort.

Travel distance and stereotactic body radiotherapy for localized prostate cancer.

BACKGROUND: Definitive stereotactic body radiotherapy (SBRT) represents an emerging and debated treatment option for patients with prostate cancer, with potential economic savings and reports of short-term efficacy since 2006. The current study sought to define national trends in definitive prostate SBRT use and determine whether patterns vary by travel distance for treatment. METHODS: The National Cancer Data Base identified 181,544 men with localized prostate cancer who were treated with definitive external beam radiotherapy from 2004 through 2012. Joinpoint regression analyzed definitive prostate SBRT trends over time, whereas multivariable logistic regression defined the odds for its receipt by travel distance for treatment. RESULTS: Definitive prostate SBRT use increased from 1.8% in 2004 to 5.9% in 2012 (P for trend <.0001), with a joinpoint for increased use noted in 2006 (P<.0001). Higher SBRT use was found to be associated with longer travel distance for treatment, younger age, white race, more affluent zip code of residence, academic treatment center, favorable disease characteristics, and fewer comorbidities (all P<.0001). Compared with travel distances <25 miles for treatment, travel distances of 25 to 50 miles and >50 miles were associated with increasing adjusted odds of receipt of definitive prostate SBRT (1.63 [95% confidence interval, 1.51-1.76] and 2.35 [95% confidence interval, 2.14-2.57], respectively; both P < .0001). CONCLUSIONS: Definitive prostate SBRT use increased more than 3-fold since 2004, with a significant increase in use coinciding with early reports of short-term efficacy. Long-distance travel for treatment was associated with greater than twice the odds of receipt of definitive prostate SBRT compared with short-distance travel, suggesting that treatment decisions with unknown long-term clinical implications may be strongly driven by sociodemographic factors. Cancer 2018;124:1141-9. © 2017 American Cancer Society.

Receipt of definitive therapy in elderly patients with unfavorable-risk prostate cancer.

BACKGROUND: Conservative management of aggressive prostate cancer in the elderly without definitive therapy has been associated with a 10-year prostate cancer-specific mortality of approximately 50%. The authors examined the prevalence of definitive therapy in elderly patients with intermediate-risk or high-risk disease. METHODS: 411,343 patients who were diagnosed from 2004 through 2012 with intermediate-risk or high-risk prostate cancer were identified in the National Cancer Database. Multivariable logistic regression adjusting for sociodemographic characteristics and comorbidity was used to examine the association between age and receipt of definitive therapy, defined as radical prostatectomy or radiotherapy, and of primary androgen deprivation therapy (ADT) among patients who did not receive definitive therapy. RESULTS: In total, 87.1% of high-risk patients and 91.9% of intermediate-risk patients received definitive therapy. When stratified by age, 93.7%, 92.1%, 90.8%, 87.6%, 80.9%, and 55.2% of high-risk patients and 96.1%, 94.7%, 93.4%, 89.7%, 82.7%, and 62.8% of intermediate-risk patients ages <60, 60 to 64, 65 to 69, 70 to 74, 75 to 79, and ≥80 years received definitive therapy, respectively. For both high-risk and intermediate-risk patients, increasing age was significantly associated with a decreased likelihood of receiving definitive therapy overall (both P < .001) and a greater likelihood of receiving primary ADT among those who did not receive definitive therapy (both P < .001). CONCLUSIONS: Older age was significantly associated with a decreased likelihood of receiving definitive therapy and an increased likelihood of receiving primary ADT in this national cohort of patients with intermediate-risk or high-risk prostate cancer. Notably, approximately 40% to 45% of patients aged ≥80 years did not receive definitive therapy. These findings are alarming given the dismal outcomes of conservatively managed unfavorable-risk prostate cancer. Cancer 2017;123:4832-40. © 2017 American Cancer Society.

National trends and determinants of proton therapy use for prostate cancer: A National Cancer Data Base study.

BACKGROUND: In the current study, the authors sought to both characterize the national trends in proton therapy use for prostate cancer and determine the factors associated with receipt of this limited resource, using what to the best of their knowledge is the largest nationwide cancer registry. METHODS: The National Cancer Data Base was used to identify 187,730 patients diagnosed with nonmetastatic prostate cancer from 2004 through 2012 who received external beam radiotherapy as their initial form of definitive therapy. Multivariable logistic regression analysis adjusted for sociodemographic and clinical factors was used to identify independent determinants of proton therapy use. RESULTS: The rate of proton therapy use increased significantly from 2.3% in 2004 to 5.2% in 2011 and 4.8% in 2012 (P value for trend <.0001). Proton therapy for prostate cancer was much more likely to be delivered at an academic compared with nonacademic center and to patients who were white, younger, healthier, from metropolitan areas, from zip codes with higher median household incomes, and who did not have an advanced stage of or high-grade disease (all P<.0001). Compared with white patients, those who were black and Hispanic were found to be significantly less likely to receive proton therapy even after robust multivariable adjustments (adjusted odds ratio, 0.20 [95% confidence interval, 0.18-0.22; P<.0001] and adjusted odds ratio, 0.57 [95% confidence interval, 0.48-0.66; P<.0001], respectively). CONCLUSIONS: The use of proton therapy to treat patients with prostate cancer more than doubled from 2004 to 2012, with striking racial disparities in its use noted despite robust multivariable adjustments. Long-term follow-up is needed to determine whether the increased use of proton therapy for prostate cancer is justified, and ongoing efforts should be made to ensure equal access to resource-limited oncologic therapies. Cancer 2016;122:1505-12. © 2016 American Cancer Society.

Risk of prostate cancer mortality in men with a history of prior cancer.

OBJECTIVES: To describe outcomes of patients with prostate cancer diagnosed after another malignancy and identify factors associated with prostate cancer death in this population, as little is known about the clinical significance of prostate cancer as a subsequent malignancy. PATIENTS AND METHODS: We studied 18 225 men diagnosed with prostate cancer after another malignancy from 1973 to 2006. We compared demographic and clinical variables, and the proportion of death from prostate cancer vs prior malignancy with t-test and chi-squared analyses. Fine and Gray's regression was used to consider the effect of treatment on prostate cancer death. We then studied a second cohort of 88 013 men with prostate cancer as a first or second malignancy to describe current diagnostic and treatment patterns. RESULTS: One in seven men died from prostate cancer in our first cohort. More died from prostate cancer following colorectal cancer (16.8% vs 13.7%), melanoma (13.4% vs 7.56%), and oral cancer (19.1% vs 4.04%), but fewer following bladder cancer, kidney cancer, lung cancer, leukaemia and non-Hodgkin's lymphoma (all P < 0.001). Prostate cancer treatment was associated with a nearly 50% lower risk of death when high-grade or high-stage (adjusted hazard ratio 0.55, 95% confidence interval [CI] 0.47-0.64). Patients who died from prostate cancer had higher grade and stage disease, and received less treatment than patients who died from prior malignancy. The second cohort showed subsequent prostate cancer had more high-risk disease (36.3% vs 22.2%, P < 0.001) and less prostate cancer treatment (adjusted odds ratio 0.872, 95% CI 0.818-0.930) than primary prostate cancer. CONCLUSIONS: Prostate cancer remains a significant cause of mortality when diagnosed as a subsequent cancer. These results suggest prostate cancer treatment should be seriously considered in patients with prior malignancies, especially those with high-grade or locally advanced prostate cancer.

Incidence and Predictors of Upgrading and Up Staging among 10,000 Contemporary Patients with Low Risk Prostate Cancer.

PURPOSE: We determined the incidence of pathological upgrading and up staging for contemporary, clinically low risk patients, and identified predictors of having occult, advanced disease to inform the selection of patients for active surveillance. MATERIALS AND METHODS: We studied 10,273 patients in the SEER database diagnosed with clinically low risk disease (cT1c/T2a, prostate specific antigen less than 10 ng/ml, Gleason 3 + 3 = 6) in 2010 to 2011 and treated with prostatectomy. The primary outcome was the incidence of upgrading to pathological Gleason score 7-10 or up staging to pathological T3-T4/N1 disease. Multivariable logistic regression of cases with complete biopsy data (5,581) identified significant predictors of upgrading or up staging, which were then used to create a risk stratification table. RESULTS: At prostatectomy 44% of cases were upgraded and 9.7% were up staged. Multivariable analysis of 5,581 patients showed age, prostate specific antigen and percent positive cores (all p < 0.001) but not race were associated with occult, advanced disease. With these variables dichotomized at the median, age older than 60 years (AOR 1.39), prostate specific antigen greater than 5.0 ng/ml (AOR 1.28) and more than 25% positive cores (AOR 1.76) were significantly associated with upgrading (all p < 0.001). Similarly, age older than 60 years (AOR 1.42), prostate specific antigen greater than 5.0 ng/ml (AOR 1.44) and more than 25% positive cores (AOR 2.26) were associated with up staging (all p < 0.001). Overall 60% of 5,581 low risk cases with prostate specific antigen 7.5 to 9.9 ng/ml and more than 25% positive cores were upgraded. This study is limited by possible bias introduced by only using patients selected for prostatectomy. CONCLUSIONS: Nearly half of clinically low risk patients harbor Gleason 7 or greater, or pT3 or greater disease, and should be risk stratified by prostate specific antigen and percent positive cores for consideration of further testing before deciding on active surveillance.

Elective Pelvic Lymph Node Radiation Therapy and the Risk of Death in Patients With Unfavorable-Risk Prostate Cancer: A Postrandomization Analysis.

PURPOSE: Although a contemporary randomized clinical trial has led to the use of whole-pelvic radiation therapy (WPRT), long-term data evaluating a potential reduction in mortality are lacking and are addressed in the current study. MATERIALS AND METHODS: From 2005 to 2015, 350 men with localized, unfavorable-risk prostate cancer (PC) were randomly assigned to receive androgen deprivation therapy (ADT) and RT plus docetaxel versus ADT and RT. Treatment of the pelvic lymph nodes was at the discretion of the treating physician. Multivariable Cox and Fine and Grays regression analyses were performed to assess whether a significant association existed between radiation treatment volume and all-cause mortality (ACM) and PC-specific mortality (PCSM), respectively, adjusting for known PC prognostic factors and comorbidity. An interaction term between age (categorized by dichotomization at 65 years to enable clinical interpretation and applicability of the results and which approximates the median (66 years [IQR, 61-70]) and radiation treatment volume was included in the analysis. RESULTS: After a median follow-up of 10.20 years (IQR, 7.96-11.41), 89 men died (25.43%); of these, 42 died of PC (47.19%). Of the 350 randomly assigned patients, 88 (25.14%) received WPRT. In men younger than 65 years, WPRT was associated with a significantly lower ACM risk (adjusted hazard ratio [AHR], 0.33 [95% CI, 0.11 to 0.97]; P = .04) and lower PCSM risk (AHR, 0.17 [95% CI, 0.02 to 1.35]; P = .09) after adjusting for covariates, whereas this was not the case for men 65 years or older. CONCLUSION: WPRT has the potential to reduce mortality in younger men with unfavorable-risk PC.

Histologically Overt Stromal Response and the Risk of Progression after Radical Prostatectomy for Prostate Cancer.

PURPOSE: Given the variable clinical course of prostate cancer and the limitations of current prognostic factors, this study was conducted to investigate the impact of a histologically overt stromal response (HOST-response) to prostate cancer on clinical outcomes after radical prostatectomy. METHODS: This retrospective analysis utilized The Cancer Genome Atlas (TCGA) to evaluate data from individuals with a confirmed diagnosis of prostate cancer who underwent radical prostatectomy and had available pathology slides. These slides were assessed for the presence of a HOST-response, similar to desmoplasia. The primary endpoint was progression-free survival (PFS). A multivariable competing risk regression analysis was used to assess whether a significant association existed between HOST-response and PFS, adjusting for known prostate cancer prognostic factors. RESULTS: Among the 348 patients analyzed, 166 (47.70%) demonstrated a HOST-response. After a median follow-up of 37.87 months (IQR: 21.20, 65.50), the presence of a HOST-response was significantly associated with a shorter PFS (SDHR, 2.10; 95% CI, 1.26 to 3.50; p = 0.004), after adjusting for covariates. CONCLUSIONS: HOST-response in prostate cancer patients treated with radical prostatectomy is significantly associated with reduced PFS, suggesting a potential benefit from adjuvant therapy and highlighting the need for further investigation in a prospective randomized clinical trial.

Prognostic Significance of the Cribriform Pattern in Prostate Cancer: Clinical Outcomes and Genomic Alterations.

PURPOSE: Given the diverse clinical progression of prostate cancer (PC) and the evolving significance of histopathological factors in its management, this study aimed to explore the impact of cribriform pattern 4 (CP4) on clinical outcomes in PC patients and examine its molecular characteristics. METHODS: This retrospective study analyzed data from The Cancer Genome Atlas (TCGA) database and included PC patients who underwent radical prostatectomy (RP) and had pathology slides available for the assessment of CP4. A multivariable competing risk regression analysis was used to assess the association between CP4 and progression-free survival (PFS) while adjusting for established PC prognostic factors. The frequency of genomic alterations was compared between patients with and without CP4 using the Fisher's exact test. RESULTS: Among the 394 patients analyzed, 129 (32.74%) had CP4. After a median follow-up of 40.50 months (IQR: 23.90, 65.60), the presence of CP4 was significantly associated with lower PFS (AHR, 1.84; 95% CI, 1.08 to 3.114; p = 0.023) after adjusting for covariates. Seven hub genes-KRT13, KRT5, KRT15, COL17A1, KRT14, KRT16, and TP63-had significantly lower mRNA expression levels in patients with CP4 compared to those without. CONCLUSIONS: PC patients with CP4 have distinct genomic alterations and are at a high risk of disease progression following RP. Therefore, these patients may benefit from additional post-RP treatments and should be the subject of a prospective randomized clinical trial.

Evaluating the Quality-of-Life Effect of Apical Spacing with Hyaluronic Acid Prior to Hypofractionated Prostate Radiation Therapy: A Secondary Analysis.

PURPOSE: Recently, a randomized trial demonstrated that a hyaluronic acid (HA) spacer placed before prostate hypofractionated intensity modulated radiation therapy improved rectal dosimetry and reduced acute grade 2+ gastrointestinal toxicity. However, 26.5% of patients receiving the spacer experienced a minimal clinically important decline (MCID) in bowel quality-of-life (QOL). The purpose of this study is to evaluate whether certain characteristics of the rectal spacer, as determined on postimplant imaging, were associated with change in bowel QOL at 3-months. METHODS AND MATERIALS: This is a secondary analysis of the 136 patients who received the HA spacer on the randomized trial. Postimplant spacer characteristics (ie, prostate-rectum spacing at superior/midgland/inferior/apex planes, symmetry, prostate volume, spacer volume) were systematically analyzed from structure sets using custom software code. Characteristics demonstrating significant associations with rectal V30 on multivariate linear regression were identified. Linear regression models were used to analyze the associations of such characteristics with change (baseline to 3 months) in both bowel and urinary QOL. RESULTS: Apical spacing (mean 9.4 (standard deviation 4.0)) was significantly smaller than spacing measurements at more superior planes. 95.6% of patients had a symmetrical implant. Apical spacing (P < .001) and prostate volume (P = .01) were significantly associated with rectal V30 on multivariate analysis. However, only apical spacing (0.38/mm; P = .01) was associated with change in bowel QOL, even with adjustment of baseline bowel score (-0.33; P < .01). Percentages of patients with bowel MCID were 14.8% for >= 10 mm versus 36.6% for <10 mm apical spacing (P = .01). Apical spacing was not associated with change in urinary QOL (-0.09; P = .72), when adjusted for baseline urinary QOL (-0.52; P < .01). CONCLUSION: Greater apical spacing was associated with improved rectal dosimetry and smaller decline in bowel QOL at 3-months. Further prospective data are needed to fully understand the ramifications of increased apical spacing.

Observer preference of artificial intelligence-generated versus clinical prostate contours for ultrasound-based high dose rate brachytherapy.

BACKGROUND: For trans-rectal ultrasound (TRUS)-based high dose rate (HDR) prostate brachytherapy, prostate contouring can be challenging due to artifacts from implanted needles, bleeding, and calcifications. PURPOSE: To evaluate the geometric accuracy and observer preference of an artificial intelligence (AI) algorithm for generating prostate contours on TRUS images with implanted needles. METHODS: We conducted a retrospective study of 150 patients, who underwent HDR brachytherapy. These patients were randomly divided into training (104), validation (26) and testing (20) sets. An AI algorithm was trained/validated utilizing the TRUS image and reference (clinical) contours. The algorithm then provided contours for the test set. For evaluation, we calculated the Dice coefficient between AI and reference prostate contours. We then presented AI and reference contours to eight clinician observers, and asked observers to select their preference. Observers were blinded to the source of contours. We calculated the percentage of cases in which observers preferred AI contours. Lastly, we evaluate whether the presence of AI contours improved the geometric accuracy of prostate contours provided by five resident observers for a 10-patient subset. RESULTS: The median Dice coefficient between AI and reference contours was 0.92 (IQR: 0.90-0.94). Observers preferred AI contours for a median of 57.5% (IQR: 47.5, 65.0) of the test cases. For resident observers, the presence of AI contours was associated with a 0.107 (95% CI: 0.086, 0.128; p < 0.001) improvement in Dice coefficient for the 10-patient subset. CONCLUSION: The AI algorithm provided high-quality prostate contours on TRUS with implanted needles. Further prospective study is needed to better understand how to incorporate AI prostate contours into the TRUS-based HDR brachytherapy workflow.

Burden of prostate cancer in the Middle East: A comparative analysis based on global cancer observatory data.

BACKGROUND: Prostate cancer represents a significant global health issue, yet our understanding of its impact in the Middle East remains limited. This study aimed to assess the incidence and mortality of prostate cancer in the Middle East, and compare these rates to those in Europe and North America. MATERIALS AND METHODS: We utilized the 2020 Global Cancer Observatory data, compiling incidence and mortality rates of prostate cancer in 20 Middle Eastern countries. We calculated mortality-to-incidence ratios (MIR) and compared the age-standardized incidence rate (ASIR) and MIR between the Middle East and the combined regions of North America and Europe. The countries were further stratified based on the Human Development Index (HDI) and income level for additional analysis. RESULTS: In 2020, the Middle East documented an estimated 51,649 new prostate cancer diagnoses, accounting for 3.7% of global cases. Despite a significantly lower ASIR in the Middle East compared with Europe and North America (10.50 vs. 21.50, p = 0.0087), the region had a higher MIR (12.35 vs. 3.00, p = 0.0476). When stratified based on HDI or income levels, there was no significant difference in MIRs; however, a significant trend of increasing MIR with decreasing HDI (p = 0.028) and income levels (p = 0.016) was observed. CONCLUSIONS: Despite a lower incidence, our analysis showed a significantly higher MIR for prostate cancer in the Middle East compared with Europe and North America. These findings underscore the unique challenges posed by prostate cancer in the Middle East and emphasize the necessity of tailored strategies to address this pressing public health issue.