Select black men are potential candidates for prostate hemi-ablation based on radical prostatectomy histopathology for intermediate-risk prostate cancer-a multicenter SEARCH cohort study.

IMPORTANCE AND OBJECTIVE: Partial gland ablation (PGA) is increasingly popular as a treatment for men with intermediate-risk prostate cancer (IR-PCa) to preserve functional outcomes while controlling their cancer. We aimed to determine the impact of race and clinical characteristics on the risk of upstaging (≥pT2c) and having adverse pathological outcomes including seminal vesicle invasion (SVI), extra prostatic extension (EPE) and lymph node invasion (LNI) at radical prostatectomy (RP) among men with IR disease eligible for PGA with hemi-ablation (HA). DESIGN: Retrospective analysis. SETTING: Multicenter. PARTICIPANTS AND MEASURES: We studied patients diagnosed with unilateral IR-PCa treated with RP between 1988 and 2020 at 9 different Veterans Affairs hospitals within the SEARCH cohort. We analyzed differences in clinicopathological characteristics and outcome variables (odds of ≥pT2c and SVI, EPE and LNI) by race using multivariable logistic regression after adjusting for covariates. RESULTS: Among 3127 patients, 33% were African American (AA) men with unilateral IR-PCa undergoing RP. Compared to non-AA men, AA individuals were younger (61 vs. 65 years, p < 0.001), presented with a higher prostate specific antigen (PSA) category (≥10 ng/ml; 34 vs. 26%, p < 0.001), and had a lower clinical stage (p < 0.001). Among the 2,798 (89.5%) with ≥pT2c stage, AA men exhibited higher ≥ pT2c rates (93 vs. 89%, p < 0.001), primarily due to increased pT2c staging (64 vs. 57%), where upstaging beyond pT2 was lower than non-AA men (29 vs. 32%). On multivariable analysis, AA men were found to have higher odds of ≥pT2c (odds ratio [OR]: 1.39 CI, 1.02-1.88, p = 0.04), lower odds of EPE (OR: 0.73 CI, 0.58-0.91, p < 0.01) and no statistically significant associations with LNI (OR: 0.79 CI, 0.42-1.46, p = 0.45) and SVI (OR: 1 CI, 0.74-1.35, p = 0.99) compared to non-AA men. On multivariable analysis, clinical features associated with higher odds of ≥pT2c were pre-operative PSA ≥ 15 (OR = 2.07, P = 0.01) and higher number of positive cores (HPC) on biopsy (OR = 1.36, P < 0.001). Similarly, PSA ≥ 15, Gleason grade ≥3 and HPC on biopsy were associated with higher odds of SVI, EPE and LNI, respectively. CONCLUSIONS: In men with IR-PCa undergoing RP, AA men demonstrated an overall higher likelihood of ≥pT2c with lower upstaging beyond pT2, lower likelihood of EPE and no significant difference in likelihood of SVI and LNI compared to non-AA men. These findings support select AA men to be potential candidates for PGA, such as HA. Clinical factors are predictive of higher pathological stage and adverse pathological outcomes at RP and could be considered when selecting candidates for PGA.

Addressing racial disparities in prostate cancer pathology prediction models: external validation and comparison of four models of pathological outcome prediction before radical prostatectomy in the multiethnic SEARCH cohort.

BACKGROUND: Certain widely used pathological outcome prediction models that were developed in tertiary centers tend to overpredict outcomes in the community setting; thus, the Michigan Urological-Surgery Improvement Collaborative (MUSIC) model was developed in general urology practice to address this issue. Additionally, the development of these models involved a relatively small proportion of Black men, potentially compromising the accuracy of predictions in this patient group. We tested the validity of the MUSIC and three widely used nomograms to compare their overall and race-stratified predictive performance. METHODS: We extracted data from 4139 (1138 Black) men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database of the Veterans Affairs health system. The predictive performance of the MUSIC model was compared to the Memorial-Sloan Kettering (MSK), Briganti-2012, and Partin-2017 models for predicting lymph-node invasion (LNI), extra-prostatic extension (EPE), and seminal vesicle invasion (SVI). RESULTS: The median PSA of Black men was higher than White men (7.8 vs. 6.8 ng/ml), although they were younger by a median of three years and presented at a lower-stage disease. MUSIC model showed comparable discriminatory capacity (AUC:77.0%) compared to MSK (79.2%), Partin-2017 (74.6%), and Briganti-2012 (76.3%), with better calibration for LNI. AUCs for EPE and SVI were 72.7% and 76.9%, respectively, all comparable to the MSK and Partin models. LNI AUCs for Black and White men were 69.6% and 79.6%, respectively, while EPE and SVI AUCs were comparable between races. EPE and LNI had worse calibration in Black men. Decision curve analysis showed MUSIC superiority over the MSK model in predicting LNI, especially among Black men. CONCLUSION: Although the discriminatory performance of all models was comparable for each outcome, the MUSIC model exhibited superior net benefit to the MSK model in predicting LNI outcomes among Black men in the SEARCH population.

Do Hispanic Puerto Rican men have worse outcomes after radical prostatectomy? Results from SEARCH.

BACKGROUND: We previously reported that outcomes after radical prostatectomy (RP) were similar among non-Hispanic Black, non-Hispanic White, and Hispanic White Veterans Affairs (VA) patients. However, prostate cancer (PC) mortality in Puerto Rican Hispanics (PRH) may be higher than in other Hispanic groups. Data focused on PRH patients is sparse; thus, we tested the association between PR ethnicity and outcomes after RP. METHODS: Analysis included men in SEARCH cohort who underwent RP (1988-2020, n = 8311). PRH patients (n = 642) were treated at the PR VA, and outcomes were compared to patients treated in the Continental US regardless of race. Logistic regression was used to test the associations between PRH and PC aggressiveness, adjusting for demographic and clinicopathological features. Multivariable Cox models were used to investigate PRH versus Continental differences in biochemical recurrence (BCR), metastases, castration-resistant PC (CRPC), and PC-specific mortality (PCSM). RESULTS: Compared to Continental patients, PRH patients had lower adjusted odds of pathological grade group ≥2 (p < 0.001), lymph node metastasis (p < 0.001), and positive margins (p < 0.001). In contrast, PRH patients had higher odds of extracapsular extension (p < 0.001). In Cox models, PRH patients had a higher risk for BCR (HR = 1.27, p < 0.001), metastases (HR = 1.49, p = 0.014), CRPC (HR = 1.80, p = 0.001), and PCSM (HR = 1.74, p = 0.011). Further adjustment for extracapsular extension and other pathological variables strengthened these findings. CONCLUSIONS: In an equal access setting, PRH RP patients generally had better pathological features, but despite this, they had significantly worse post-treatment outcomes than men from the Continental US, regardless of race. The reasons for the poorer prognosis among PRH men require further research.

Contemporary risk of biochemical recurrence after radical prostatectomy in the active surveillance era.

OBJECTIVES: To assess whether contemporary risks of biochemical recurrence (BCR) after radical prostatectomy (RP) in the AS era differ from historical estimates due to changes in tumor risk case mix and improvements in risk stratification. MATERIALS AND METHODS: We sampled 6,682 men who underwent RP for clinically localized disease between 2000 and 2017 from the VA SEARCH database. Kaplan Meier analysis was used to calculate incidence of BCR before and after 2010 overall and within tumor risk subgroups. Multivariable Cox proportional hazard regression analysis including an interaction term between era and tumor risk was used to compare risk of BCR before and after 2010 overall and across tumor risk subgroups. RESULTS: About 3,492 (52%) and 3,190 (48%) men underwent RP before and after 2010, respectively. In a limited multivariable model excluding tumor risk, overall BCR risk was higher post-2010 vs. pre-2010 (HR: 1.15, 95%CI: 1.05-1.25; 40% vs 36% at 8 years post-RP). However, this effect was eliminated after correcting for tumor risk (HR: 0.95, 95%CI: 0.87-1.04), suggesting that differences in tumor risk between eras mediated the change. Yet, within tumor-risk subgroups, BCR risk was significantly lower for favorable intermediate-risk (HR: 0.76, 95%CI:0.60-0.96) and unfavorable intermediate-risk PC (HR: 0.78, 95%CI: 0.67-0.90), but significantly higher for high-risk PC (HR: 1.22, 95%CI: 1.07-1.38) in the post-2010 era. 8-year risks of BCR in the post-2010 era were 21% (95%CI: 16%-25%), 25% (95%CI: 20%-30%), 41% (95%CI: 37%-46%), and 60% (95%CI: 56%-64%) for low-, FIR-, UIR-, and high-risk disease, respectively. Limitations include limited long-term follow-up in the post-2010 subgroup. CONCLUSIONS: Overall BCR risk has increased in the AS era, driven by a higher risk case mix and increased BCR risk among high-risk patients. Physicians should quote contemporary estimates of BCR when counseling patients.

Postradical prostatectomy prostate-specific antigen outcomes after 6 versus 18 months of perioperative androgen-deprivation therapy in men with localized, unfavorable intermediate-risk or high-risk prostate cancer: Results of part 2 of a randomized phase 2 trial.

BACKGROUND: Patients with localized, unfavorable intermediate-risk and high-risk prostate cancer have an increased risk of relapse after radical prostatectomy (RP). The authors previously reported on part 1 of this phase 2 trial testing neoadjuvant apalutamide, abiraterone, prednisone, plus leuprolide (AAPL) or abiraterone, prednisone, and leuprolide (APL) for 6 months followed by RP. The results demonstrated favorable pathologic responses (tumor <5 mm) in 20.3% of patients (n = 24 of 118). Herein, the authors report the results of part 2. METHODS: For part 2, patients were randomized 1:1 to receive either AAPL for 12 months (arm 2A) or observation (arm 2B), stratified by neoadjuvant therapy and pathologic tumor classification. The primary end point was 3-year biochemical progression-free survival. Secondary end points included safety and testosterone recovery (>200 ng/dL). RESULTS: Overall, 82 of 118 patients (69%) enrolled in part 1 were randomized to part 2. A higher proportion of patients who were not randomized to adjuvant therapy had a favorable prostatectomy pathologic response (32.3% in nonrandomized patients compared with 17.1% in randomized patients). In the intent-to-treat analysis, the 3-year biochemical progression-free survival rate was 81% for arm 2A and 72% for arm 2B (hazard ratio, 0.81; 90% confidence interval, 0.43-1.49). Of the randomized patients, 81% had testosterone recovery in the AAPL group compared with 95% in the observation group, with a median time to recovery of <12 months in both arms. CONCLUSIONS: In this study, because 30% of patients declined adjuvant treatment, part B was underpowered to detect differences between arms. Future perioperative studies should be biomarker-directed and include strategies for investigator and patient engagement to ensure compliance with protocol procedures.

What is the Incidence of Kidney Stones after Chemotherapy in Patients with Lymphoproliferative or Myeloproliferative Disorders?

Introduction This study describes the incidence and risk factors of de novo nephrolithiasis among patients with lymphoproliferative or myeloproliferative diseases who have undergone chemotherapy. Materials and Methods From 2001 to 2011, patients with lymphoproliferative or myeloproliferative disorders treated with chemotherapy were retrospectively identified. The incidence of image proven nephrolithiasis after chemotherapy was determined. Demographic and clinical variables were recorded. Patients with a history of nephrolithiasis prior to chemotherapy were excluded. The primary outcome was incidence of nephrolithiasis, and secondary outcomes were risk factors predictive of de novo stone. Comparative statistics were used to compare demographic and disease specific variables for patients who developed de novo stones versus those who did not. Results A total of 1,316 patients were identified and the incidence of de novo nephrolithiasis was 5.5% (72/1316; symptomatic stones 1.8% 24/1316). Among patients with nephrolithiasis, 72.2% had lymphoproliferative disorders, 27.8% had myeloproliferative disorders, and 25% utilized allopurinol. The median urinary pH was 5.5, and the mean serum uric acid, calcium, potassium and phosphorus levels were 7.5, 9.6, 4.3, and 3.8 mg/dL, respectively. In univariate analysis, mean uric acid (p=0.013), calcium (p<0.001)), and potassium (p=0.039) levels were higher in stone formers. Diabetes mellitus (p<0.001), hypertension (p=0.003), and hyperlipidemia (p<0.001) were more common in stone formers. In multivariate analysis, diabetes mellitus, hyperuricemia, and hypercalcemia predicted stone. Conclusions We report the incidence of de novo nephrolithiasis in patients who have undergone chemotherapy. Diabetes mellitus, hyperuricemia, and hypercalcemia are patient-specific risk factors that increase the odds of developing an upper tract stone following chemotherapy. .

High serum folate is associated with reduced biochemical recurrence after radical prostatectomy: Results from the SEARCH Database

Introduction To analyze the association between serum levels of folate and risk of biochemical recurrence after radical prostatectomy among men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Materials and Methods Retrospective analysis of 135 subjects from the SEARCH database treated between 1991-2009 with available preoperative serum folate levels. Patients' characteristics at the time of the surgery were analyzed with ranksum and linear regression. Uni- and multivariable analyses of folate levels (log-transformed) and time to biochemical recurrence were performed with Cox proportional hazards. Results The median preoperative folate level was 11.6ng/mL (reference = 1.5-20.0ng/mL). Folate levels were significantly lower among African-American men than Caucasians (P = 0.003). In univariable analysis, higher folate levels were associated with more recent year of surgery (P < 0.001) and lower preoperative PSA (P = 0.003). In univariable analysis, there was a trend towards lower risk of biochemical recurrence among men with high folate levels (HR = 0.61, 95%CI = 0.37-1.03, P = 0.064). After adjustments for patients characteristics' and pre- and post-operative clinical and pathological findings, higher serum levels of folate were independently associated with lower risk for biochemical recurrence (HR = 0.42, 95%CI = 0.20-0.89, P = 0.023). Conclusion In a cohort of men undergoing radical prostatectomy at several VAs across the country, higher serum folate levels were associated with lower PSA and lower risk for biochemical failure. While the source of the folate in the serum in this study is unknown (i.e. diet vs. supplement), these findings, if confirmed, suggest a potential role of folic acid supplementation or increased consumption of folate rich foods to reduce the risk of recurrence. .

The effect of kidney morcellation on operative time, incision complications, and postoperative analgesia after laparoscopic nephrectomy

INTRODUCTION: Compare the outcomes between kidney morcellation and two types of open specimen extraction incisions, several covariates need to be taken into consideration that have not yet been studied. MATERIALS AND METHODS: We retrospectively reviewed 153 consecutive patients who underwent laparoscopic nephrectomy at our institution, 107 who underwent specimen morcellation and 46 with intact specimen removal, either those with connected port sites with a muscle-cutting incision and those with a remote, muscle-splitting incision. Operative time, postoperative analgesia requirements, and incisional complications were evaluated using univariate and multivariate analysis, comparing variables such as patient age, gender, body mass index (BMI), laterality, benign versus cancerous renal conditions, estimated blood loss, specimen weight, overall complications, and length of stay. RESULTS: There was no significant difference for operative time between the 2 treatment groups (p = 0.65). Incision related complications occurred in 2 patients (4.4 percent) from the intact specimen group but none in the morcellation group (p = 0.03). Overall narcotic requirement was lower in patients with morcellated (41 mg) compared to intact specimen retrieval (66 mg) on univariate (p = 0.03) and multivariate analysis (p = 0.049). Upon further stratification, however, there was no significant difference in mean narcotic requirement between the morcellation and muscle-splitting incision subgroup (p = 0.14). CONCLUSION: Morcellation does not extend operative time, and is associated with significantly less postoperative pain compared to intact specimen retrieval overall, although this is not statistically significant if a remote, muscle-splitting incision is made. Morcellation markedly reduces the risk of incisional-related complications.