Impact of PSA nadir, PSA response and time to PSA nadir on overall survival in real-world setting of metastatic hormone-sensitive prostate cancer patients.

BACKGROUND: To evaluate the impact of prostate-specific antigen (PSA) nadir, PSA response and time to PSA nadir (TTN) in metastatic hormone-sensitive prostate cancer (mHSPC) patients on overall survival (OS) in the era of combination therapies. METHODS: Different PSA nadir cut-offs (including ultra-low PSA) were tested for OS analyses. Additionally, PSA response ≥99% was evaluated, as well as TTN categorized as <3 versus 3-6 versus 6-12 versus >12 months. Multivariable Cox regression models predicted the value of PSA nadir cut-offs, PSA response and TTN on OS. Sensitivity analyses were performed in de novo and high volume mHSPC patients. RESULTS: Of 238 eligible patients, PSA cut-offs of <0.2 versus 0.2-4.0 versus >4.0 ng/mL differed significantly regarding median OS (96 vs. 56 vs. 44 months, p < 0.01), as well as in subgroup analyses of de novo mHSPC patients and multivariable Cox regression models. A more stringent PSA cut-off of <0.02 versus 0.02-0.2 versus >0.2 ng/mL also yielded significant median OS differences (not reached vs. 96 vs. 50 months, p < 0.01), even after additional multivariable adjustment. A PSA response ≥99% was also significantly associated with better OS than counterparty with <99% response, even after multivariable adjustment (both p < 0.02). When TTN groups were compared, patients with longer TTN harbored more extended OS than those with short TTN (<3 vs. 3-6 vs. 6-12 vs. >12 months: 34 vs. 50 vs. 67 vs. 96 months, p < 0.01). Virtually similar results were observed in sensitivity analyses for high volume mHSPC patients. CONCLUSIONS: In times of combination therapies for mHSPC, a PSA nadir of respectively, <0.2 and <0.02 ng/mL are associated with best OS rates. Moreover, a relative PSA response ≥99% and a longer TTN are clinical important proxies for favorable OS estimates.

Metastatic Squamous Cell Carcinoma of the Urinary Bladder: Urgent Call for New Therapies.

BACKGROUND: Squamous cell carcinoma (SCC) of the urinary bladder is the most common non-urothelial variant histology. Currently, upfront radical cystectomy is the gold standard for non-metastatic SCC of the bladder. However, several studies have shown that SCC of the bladder is associated with higher aggressiveness and worse survival outcomes, such as progression-free and cancer-specific survival, relative to the urothelial histological subtype. Moreover, metastatic SCC seems to poorly respond to systemic treatments and/or radiotherapy. SUMMARY: This review summarizes the current knowledge and medical evidence regarding local and systematic treatment of mSCC of the bladder, including a case series of four initially locally advanced and later metastatic SCC patients of our tertiary care hospital. KEY MESSAGES: Despite being the second most common variant histology of bladder cancer, current therapies for SCC do not provide satisfactory therapeutic responses.

Real-world evidence of tumor and patient characteristics and survival with avelumab maintenance after chemotherapy for advanced and metastatic urothelial carcinoma.

PURPOSE: Despite the prospective randomized controlled JAVELIN Bladder 100 trial, no real-world evidence exists regarding tumor characteristics, adverse events (AE) and survival of avelumab maintenance (AVM) treated patients with partial/complete response or stable disease after previous platinum-based chemotherapy for advanced/metastatic urothelial carcinoma (mUC). METHODS: We relied on our institutional database to identify mUC patients who received AVM between 01/2021-12/2023. The main outcomes consisted of overall (OS) and progression-free survival (PFS) and were computed by Kaplan-Meier estimates. Stratification was performed according to PD-L1 status. RESULTS: Overall, 24 AVM patients were identified at a median age of 71 (interquartile range [IQR]: 67-76) years of which 67% were males. Of these, 63%, 21% and 17% received AVM therapy for bladder cancer and upper tract urothelial carcinoma or both, respectively. PD-L1 status was positive in 45% of patients. During AVM treatment, AEs were observed in 33% of patients, however, were limited to ≤2 grade AEs. At a median follow-up of eight (IQR 4-20) months, 71% of patients had progressed under AVM with median PFS of 6.2 months (CI: 3.2-18.2). Median OS was 13.4 (CI: 6.9-not reached [NR]) months. One-year OS after AVM was 52%. In PD-L1 positive patients, median PFS and OS were 6.4 (CI: 2.7 - NR) months and 13.4 (CI: 7.7 months - NR), respectively. CONCLUSION: AVM is associated with moderate AE rates. Despite similarities in baseline characteristics compared to trial-selected JAVELIN Bladder 100 mUC patients, AVM resulted in longer/similar PFS but significantly shorter OS in in real-world setting.

Cardiovascular Disease and Chronic Pulmonary Disease Increase the Risk of Short-Term Major Postoperative Complications after Robotic-Assisted Radical Prostatectomy.

Background and objectives: Certain comorbidities may be associated with a higher risk of complications after robotic-assisted radical prostatectomy. Material and Methods: Relying on a tertiary care database, we identified robotic-assisted radical prostatectomy patients (January 2014-March 2023). Short-term major postoperative complications were defined according to Clavien Dindo as ≥IIIa within 30 days after robotic-assisted radical prostatectomy. Results: Of 1148 patients, the rates of postoperative Clavien Dindo IIIa, Clavien Dindo IIIb, Clavien Dindo IVa, and Clavien Dindo IVb complications were 3.3%, 1.4%, 0.3%, and 0.2%, respectively. Of those, 28 (47%) had lymphoceles, and 8 (13%) had bleeding-associated complications. Patients with cardiovascular disease (8 vs. 4%) or chronic pulmonary disease (13 vs. 5%) were more likely to have complications. In multivariable logistic regression models, cardiovascular disease (odds ratio: 1.78; p = 0.046) and chronic pulmonary disease (odds ratio: 3.29; p = 0.007) remained associated with an increased risk of postoperative complications. Conclusions: Complications after robotic-assisted radical prostatectomy are predominantly manageable without anesthesia. Concomitant cardiovascular disease and chronic pulmonary disease were both associated with a higher risk of postoperative complications.

Real-world evidence of outcomes of oligometastatic hormone-sensitive prostate cancer patients treated with metastasis-directed therapy.

OBJECTIVE: To investigate characteristics and outcomes of oligometastatic hormone-sensitive prostate cancer (mHSPC) patients undergoing metastases-directed therapy (MDT) with external beam radiation therapy (EBRT). MATERIALS AND METHODS: We relied on an institutional tertiary-care database to identify mHSPC patients who underwent EBRT as MDT between 12/2019 and 12/2022. Main outcomes consisted of progression to metastatic castration-resistant prostate cancer (mCRPC) and overall mortality (OM). Oligometastatic was defined as ≤3 metastases and bone and/or lymph node deposits were treated with conventional doses up to 54 Gy or with hypofractionated stereotactic regimes of median 24 Gy (20-27 Gy). RESULTS: Overall, 37 patients treated with EBRT as MDT were identified. The median follow-up was 13 months. Median age at MDT was 71 years and 84% exhibited ECOG performance status 0. The median baseline PSA at diagnosis was 10 ng/mL. Overall, primary local therapy consisted of radical prostatectomy (65%), followed by external beam radiation therapy to the prostate (11%), focal therapy (8%), and palliative transurethral resection of the prostate (5%). Overall, 32% exhibited de novo oligometastatic mHSPC. Bone metastases were present in 78% versus 19% lymph node metastases versus 3% both. The distribution of targeted oligo-metastases was 62% versus 38% for respectively one metastasis versus more than one metastasis. Androgen deprivation therapy (ADT) was combined with MDT in 84%. Moreover, 19% received combination therapy with apalutamide/enzalutamide and 12% with abiraterone or docetaxel. The median time to mCRPC was 50 months. In incidence analyses, 13% developed mCRPC after 24 months. OM after 24 months was 15% in mHSPC patients receiving MDT. Significant OM differences were observed after stratification into targeted metastatic burden (<0.05). No high-grade adverse events were recorded during MDT. CONCLUSION: Our real-world data suggest that MDT represents a safe treatment option for well-selected oligometastatic mHSPC patients.

Effect of positive surgical margins at radical prostatectomy on cancer-specific mortality in high/very high-risk prostate cancer patients with Gleason Grade Group 4-5.

BACKGROUND: The effect of positive surgical margins (PSM) on cancer specific mortality (CSM) in high/very high-risk (HR/VHR) prostate cancer (PCa) with aggressive Gleason Grade Group (GGG) is unknown. We tested PSM effect on CSM in this setting, in addition to testing of radiotherapy (RT) benefit in PSM patients. METHODS: We relied on Surveillance, Epidemiology, and End Results database (2010-2015), focusing on HR/VHR patients with exclusive GGG 4-5 at radical prostatectomy (RP). Kaplan-Meier plots and multivariable Cox regression models tested the relationship between PSM and CSM. Moreover, the effect of RT on CSM was explored in PSM patients. RESULTS: Of 3383 HR/VHR patients, 15.1% (n = 511) exhibited PSM. Patients with PSM harbored higher rates of GGG 5 (60.1% vs. 50.9%, p < 0.001), pathologic tumor stage T3a (69.1% vs. 45.2%, p < 0.001) and lymph node involvement (14.1% vs. 9.4%, p < 0.001), relative to patients without PSM. PSM rates decreased over time (2010-2015) from 16.0% to 13.6%. Seven-year CSM-free survival rates were 91.6% versus 95.7% in patients with and without PSM, respectively. In multivariable Cox regression models, PSM was an independent predictor of CSM (hazard ratio = 1.6, p = 0.040) even after adjustment for age, prostate specific antigen, pathologic tumor stage and lymph node status. Finally, in PSM patients, RT delivery did not reduce CSM in either univariable or multivariable Cox regression models. CONCLUSIONS: In HR/VHR PCa patients with exclusive GGG 4-5, PSM at RP adversely affect survival. Moreover, RT has no protective effect on CSM. In consequence, lowest possible PSM rates are crucial in such patients.

The association of type and number of high-risk criteria with cancer specific mortality in prostate cancer patients treated with radiotherapy.

BACKGROUND: To assess the association between of type and number of D'Amico high-risk criteria (DHRCs) with rates of cancer-specific mortality (CSM) in prostate cancer (PCa) patients treated with external beam radiotherapy (RT). METHODS: In the Surveillance, Epidemiology, and End Results database (2004-2016), we identified 34,908 RT patients with at least one DHRCs, namely prostate-specific antigen (PSA) >20 ng/dL (hrPSA), biopsy Grade Group (hrGG) 4-5, clinical T stage (hrcT) ≥T2c. Multivariable Cox regression models (CRM), as well as competing risks regression (CRR) model, which further adjust for other cause mortality, tested the association between DHRCs and 5-year CSM. RESULTS: Of 34,908 patients, 14,777 (42%) exclusively harbored hrGG, 5641 (16%) hrPSA, 4390 (13%) had hrcT. Only 8238 (23.7%) harbored any combination of two DHRCs and 1862 (5.3%) had all three DHRCs. Five-year CSM rates ranged from 2.4% to 5.0% when any individual DHRC was present (hrcT, hrPSA, hrGG, in that order), versus 5.2% to 10.5% when two DHRCs were present (hrPSA+hrcT, hrcT+hrGG, hrPSA+hrGG, in that order) versus 14.4% when all three DHRCs were identified. In multivariable CRM hazard ratios relative to hrcT ranged from 1.07 to 1.76 for one DHRC, 2.20 to 3.83 for combinations of two DHRCs, and 5.11 for all three DHRCs. Multivariable CRR yielded to virtually the same results. CONCLUSIONS: Our study indicates a stimulus-response effect according to the type and number of DHRCs. This indicates potential for risk-stratification within HR PCa patients that could be applied in clinical decision making to increase or reduce treatment intensity.

Cancer-specific Mortality After Cryoablation vs Heat-based Thermal Ablation in T1a Renal Cell Carcinoma.

PURPOSE: Guidelines suggest less favorable cancer control outcomes for local tumor destruction in T1a renal cell carcinoma patients with tumor size 3.1-4 cm. We compared cancer-specific mortality between cryoablation vs heat-based thermal ablation in patients with tumor size 3.1-4 cm, as well as in patients with tumor size ≤3 cm. MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2018), we identified patients with clinical T1a stage renal cell carcinoma treated with cryoablation or heat-based thermal ablation. After up to 2:1 ratio propensity score matching between patients treated with cryoablation vs heat-based thermal ablation, we addressed cancer-specific mortality relying on competing risks regression models, adjusted for other-cause mortality and other covariates (age, tumor size, tumor grade, and histological subtype). RESULTS: Of 1,468 assessable patients with tumor size 3.1-4 cm, 1,080 vs 388 were treated with cryoablation vs heat-based thermal ablation, respectively. After up to 2:1 propensity score matching that resulted in 757 cryoablations vs 388 heat-based thermal ablations, in multivariable competing risks regression models, heat-based thermal ablation was associated with higher cancer-specific mortality (HR:2.02, P < .001), relative to cryoablation. Of 4,468 assessable patients with tumor size ≤3 cm, 3,354 vs 1,114 were treated with cryoablation vs heat-based thermal ablation, respectively. After up to 2:1 propensity score matching that resulted in 2,217 cryoablations vs 1,114 heat-based thermal ablations, in multivariable competing risks regression models, heat-based thermal ablation was not associated with higher cancer-specific mortality (HR:1.13, P = .5) relative to cryoablation. CONCLUSIONS: Our findings corroborated that in cT1a patients with tumor size 3.1-4 cm, cancer-specific mortality is twofold higher after heat-based thermal ablation vs cryoablation. Conversely, in patients with tumor size ≤3 cm either ablation technique is equally valid. These findings should be considered at clinical decision making and informed consent.

In-Hospital Venous Thromboembolism and Pulmonary Embolism After Major Urologic Cancer Surgery.

BACKGROUND: This study aimed to test for temporal trends of in-hospital venous thromboembolism (VTE) and pulmonary embolism (PE) after major urologic cancer surgery (MUCS). METHODS: In the Nationwide Inpatient Sample (NIS) database (2010-2019), this study identified non-metastatic radical cystectomy (RC), radical prostatectomy (RP), radical nephrectomy (RN), and partial nephrectomy (PN) patients. Temporal trends of VTE and PE and multivariable logistic regression analyses (MLR) addressing VTE or PE, and mortality with VTE or PE were performed. RESULTS: Of 196,915 patients, 1180 (1.0%) exhibited VTE and 583 (0.3%) exhibited PE. The VTE rates increased from 0.6 to 0.7% (estimated annual percentage change [EAPC] + 4.0%; p = 0.01). Conversely, the PE rates decreased from 0.4 to 0.2% (EAPC - 4.5%; p = 0.01). No difference was observed in mortality with VTE (EAPC - 2.1%; p = 0.7) or with PE (EAPC - 1.2%; p = 0.8). In MLR relative to RP, RC (odds ratio [OR] 5.1), RN (OR 4.5), and PN (OR 3.6) were associated with higher VTE risk (all p < 0.001). Similarly in MLR relative to RP, RC (OR 4.6), RN (OR 3.3), and PN (OR 3.9) were associated with higher PE risk (all p < 0.001). In MLR, the risk of mortality was higher when VTE or PE was present in RC (VTE: OR 3.7, PE: OR  4.8; both p < 0.001) and RN (VTE: OR 5.2, PE: OR  8.3; both p < 0.001). CONCLUSIONS: RC, RN, and PN predisposes to a higher VTE and PE rates than RP. Moreover, among RC and RN patients with either VTE or PE, mortality is substantially higher than among their VTE or PE-free counterparts.

Optimizing identification of consensus molecular subtypes in muscle-invasive bladder cancer: a comparison of two sequencing methods and gene sets using FFPE specimens.

BACKGROUND: Molecular subtypes predict prognosis in muscle-invasive bladder cancer (MIBC) and are explored as predictive markers. To provide a common base for molecular subtyping and facilitate clinical applications, a consensus classification has been developed. However, methods to determine consensus molecular subtypes require validation, particularly when FFPE specimens are used. Here, we aimed to evaluate two gene expression analysis methods on FFPE samples and to compare reduced gene sets to classify tumors into molecular subtypes. METHODS: RNA was isolated from FFPE blocks of 15 MIBC patients. Massive analysis of 3' cDNA ends (MACE) and the HTG transcriptome panel (HTP) were used to retrieve gene expression. We used normalized, log2-transformed data to call consensus and TCGA subtypes with the consensusMIBC package for R using all available genes, a 68-gene panel (ESSEN1), and a 48-gene panel (ESSEN2). RESULTS: Fifteen MACE-samples and 14 HTP-samples were available for molecular subtyping. The 14 samples were classified as Ba/Sq in 7 (50%), LumP in 2 (14.3%), LumU in 1 (7.1%), LumNS in 1 (7.1%), stroma-rich in 2 (14.3%) and NE-like in 1 (7.1%) case based on MACE- or HTP-derived transcriptome data. Consensus subtypes were concordant in 71% (10/14) of cases when comparing MACE with HTP data. Four cases with aberrant subtypes had a stroma-rich molecular subtype with either method. The overlap of the molecular consensus subtypes with the reduced ESSEN1 and ESSEN2 panels were 86% and 100%, respectively, with HTP data and 86% with MACE data. CONCLUSION: Determination of consensus molecular subtypes of MIBC from FFPE samples is feasible using various RNA sequencing methods. Inconsistent classification mainly involves the stroma-rich molecular subtype, which may be the consequence of sample heterogeneity with (stroma)-cell sampling bias and highlights the limitations of bulk RNA-based subclassification. Classification is still reliable when analysis is reduced to selected genes.

Comparison of peri- and intraoperative outcomes of open vs robotic-assisted partial nephrectomy for renal cell carcinoma: a propensity-matched analysis.

BACKGROUND: Partial nephrectomy (PN) is the gold standard surgical treatment for resectable renal cell carcinoma (RCC) tumors. However, the decision whether a robotic (RAPN) or open PN (OPN) approach is chosen is often based on the surgeon's individual experience and preference. To overcome the inherent selection bias when comparing peri- and postoperative outcomes of RAPN vs. OPN, a strict statistical methodology is needed. MATERIALS AND METHODS: We relied on an institutional tertiary-care database to identify RCC patients treated with RAPN and OPN between January 2003 and January 2021. Study endpoints were estimated blood loss (EBL), length of stay (LOS), rate of intraoperative and postoperative complications, and trifecta. In the first step of analyses, descriptive statistics and multivariable regression models (MVA) were applied. In the second step of analyses, to validate initial findings, MVA were applied after 2:1 propensity-score matching (PSM). RESULTS: Of 615 RCC patients, 481 (78%) underwent OPN vs 134 (22%) RAPN. RAPN patients were younger and presented with a smaller tumor diameter and lower RENAL-Score sum, respectively. Median EBL was comparable, whereas LOS was shorter in RAPN vs. OPN. Both intraoperative (27 vs 6%) and Clavien-Dindo > 2 complications (11 vs 3%) were higher in OPN (both < 0.05), whereas achievement of trifecta was higher in RAPN (65 vs 54%; p = 0.028). In MVA, RAPN was a significant predictor for shorter LOS, lower rates of intraoperative and postoperative complications as well as higher trifecta rates. After 2:1 PSM with subsequent MVA, RAPN remained a statistical and clinical predictor for lower rates of intraoperative and postoperative complications and higher rates of trifecta achievement but not LOS. CONCLUSIONS: Differences in baseline and outcome characteristics exist between RAPN vs. OPN, probably due to selection bias. However, after applying two sets of statistical analyses, RAPN seems to be associated with more favorable outcomes regarding complications and trifecta rates.

Epidemiology of Unconventional Histological Subtypes of Urethral Cancer.

INTRODUCTION: The aim of the study was to examine cancer-specific mortality (CSM) of unconventional urethral cancers. METHODS: Within the SEER (2004-2016) database, we analyzed CSM of 165 patients with unconventional urethral-cancer histology. Kaplan-Meier plots were used to test the effect of unconventional histologies in urethral cancer on CSM. RESULTS: Of 165 eligible patients, the Mullerian type accounted for 55 (33.3%) versus melanocytic (26.7%) versus neuroendocrine 25 (15.2%) versus lymphoma 22 (13.3%) versus mesenchymal/sarcoma 15 (9.1%) versus spindle cell 4 (2.1%) patients. Median age at diagnosis was 81 years in spindle cell, 75 in melanocytic, 74 in neuroendocrine and mesenchymal/sarcoma, 67 in lymphoma, and 62 years Mullerian type (p < 0.001). Of all, 116 (70.3%) were female. The Mullerian type exhibited the highest female ratio (96.4%) versus the lowest female ratio in neuroendocrine (24.0%). The Mullerian type was most frequent in African-American females. In Caucasian females, the melanocytic type was most frequent (49.1%). In African-American (38.9%) and Caucasian males (33.3%), neuroendocrine histology was most frequent. Three-year CSM was, respectively, 27.5%, 23.1% 22.3%, 20.5%, and 16.1% for melanocytic, mesenchymal/sarcoma, Mullerian type, neuroendocrine, and lymphoma histology. Median cancer-specific survival was 106 versus 10 months for combined nonmetastatic versus metastatic nonconventional histologies. CONCLUSION: Important age, sex, racial/ethnic group distribution, and survival differences exist between each unconventional urethral-cancer histological subtypes.

Impact of Age on Long-Term Urinary Continence after Robotic-Assisted Radical Prostatectomy.

Aim and Objectives: We aimed to test the impact of age on long-term urinary continence (≥12 months) in patients undergoing robotic-assisted radical prostatectomy. Methods and Materials: We relied on an institutional tertiary-care database to identify the patients who underwent robotic-assisted radical prostatectomy between January 2014 and January 2021. Patients were divided into three age groups: age group one (≤60 years), age group two (61-69 years) and age group three (≥70 years). Multivariable logistic regression models tested the differences between the age groups in the analyses addressing long-term urinary continence after robotic-assisted radical prostatectomy. Results: Of the 201 prostate cancer patients treated with robotic-assisted radical prostatectomy, 49 (24%) were assigned to age group one (≤60 years), 93 (46%) to age group two (61-69 years) and 59 (29%) to age group three (≥70 years). The three age groups differed according to long-term urinary continence: 90% vs. 84% vs. 69% for, respectively, age group one vs. two vs. three (p = 0.018). In the multivariable logistic regression, age group one (Odds Ratio (OR) 4.73, 95% CI 1.44-18.65, p = 0.015) and 2 (OR 2.94; 95% CI 1.23-7.29; p = 0.017) were independent predictors for urinary continence, compared to age group three. Conclusion: Younger age, especially ≤60 years, was associated with better urinary continence after robotic-assisted radical prostatectomy. This observation is important at the point of patient education and should be discussed in informed consent.

Rates of metastatic prostate cancer in newly diagnosed patients: Numbers needed to image according to risk level.

BACKGROUND: The numbers needed to image to identify pelvic lymph node and/or distant metastases in newly diagnosed prostate cancer (PCa) patients according to risk level are unknown. METHODS: Relying on Surveillance, Epidemiology, and End Results (2010-2016), we tabulated rates and proportions of patients with (a) lymph node or (b) distant metastases according to National Comprehensive Cancer Network (NCCN) risk level and calculated the number needed to image (NNI) for both endpoints. Multivariable logistic regression analyses were performed. RESULTS: Of 145,939 newly diagnosed PCa patients assessable for analyses of pelvic lymph node metastases (cN1), 4559 (3.1%) harbored cN1 stage: 13 (0.02%), 18 (0.08%), 63 (0.3%), 512 (2.8%), and 3954 (14.9%) in low, intermediate favorable, intermediate unfavorable, high, and very high-risk levels. These resulted in NNI of 4619, 1182, 319, 35, and 7, respectively. Of 181,109 newly diagnosed PCa patients assessable for analyses of distant metastases (M1a-c ), 8920 (4.9%) harbored M1a-c stage: 50 (0.07%), 45 (0.1%), 161 (0.5%), 1290 (5.1%), and 7374 (22.0%) in low, intermediate favorable, intermediate unfavorable, high, and very high-risk. These resulted in NNI of 1347, 602, 174, 20, and 5, respectively. CONCLUSIONS: Our observations perfectly validated the NCCN recommendations for imaging in newly diagnosed high and very high-risk PCa patients. However, in unfavorable intermediate-risk PCa patients, in whom bone and soft tissue imaging is recommended, the NNI might be somewhat elevated to support routine imaging in clinical practice.

Effect of chemotherapy in metastatic prostate cancer according to race/ethnicity groups.

BACKGROUND: No North-American study tested the survival benefit of chemotherapy in de novo metastatic prostate cancer according to race/ethnicity. We addressed this void. METHODS: We identified de novo metastatic prostate cancer patients within the Surveillance, Epidemiology, and End Results database (2014-2015). Separate and specific Kaplan-Meier plots and Cox regression models tested for overall survival differences between chemotherapy-exposed versus chemotherapy-naïve patients in four race/ethnicity groups: Caucasian versus African-American versus Hispanic/Latino vs Asian. Race/ethnicity specific propensity score matching was applied. Here, additional landmark analysis was performed. RESULTS: Of 4232 de novo metastatic prostate cancer patients, 2690 (63.3%) were Caucasian versus 783 (18.5%) African-American versus 504 (11.8%) Hispanic/Latino versus 257 (6.1%) Asian. Chemotherapy rates were: 21.3% versus 20.8% versus 21.0% versus 20.2% for Caucasians versus African-Americans versus Hispanic/Latinos versus Asians, respectively. At 30 months of follow-up, overall survival rates between chemotherapy-exposed versus chemotherapy-naïve patients were 61.5 versus 53.2% (multivariable hazard ratio [mHR]: 0.76, 95 confidence interval [CI]: 0.63-0.92, p = 0.004) in Caucasians, 55.2 versus 51.6% (mHR: 0.76, 95 CI: 0.54-1.07, p = 0.11) in African-Americans, 62.8 versus 57.0% (mHR: 1.11, 95 CI: 0.73-1.71, p = 0.61) in Hispanic/Latinos and 77.7 versus 65.0% (mHR: 0.31, 95 CI: 0.11-0.89, p = 0.03) in Asians. Virtually the same findings were recorded after propensity score matching within each race/ethnicity group. CONCLUSIONS: Caucasian and Asian de novo metastatic prostate cancer patients exhibit the greatest overall survival benefit from chemotherapy exposure. Conversely, no overall survival benefit from chemotherapy exposure could be identified in either African-Americans or Hispanic/Latinos. Further studies are clearly needed to address these race/ethnicity specific disparities.

Non-organ confined stage and upgrading rates in exclusive PSA high-risk prostate cancer patients.

BACKGROUND: The pathological stage of prostate cancer with high-risk prostate-specific antigen (PSA) levels, but otherwise favorable and/or intermediate risk characteristics (clinical T-stage, Gleason Grade group at biopsy [B-GGG]) is unknown. We hypothesized that a considerable proportion of such patients will exhibit clinically meaningful GGG upgrading or non-organ confined (NOC) stage at radical prostatectomy (RP). MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2010-2015) we identified RP-patients with cT1c-stage and B-GGG1, B-GGG2, or B-GGG3 and PSA 20-50 ng/ml. Rates of GGG4 or GGG5 and/or rates of NOC stage (≥ pT3 and/or pN1) were analyzed. Subsequently, separate univariable and multivariable logistic regression models tested for predictors of NOC stage and upgrading at RP. RESULTS: Of 486 assessable patients, 134 (28%) exhibited B-GGG1, 209 (43%) B-GGG2, and 143 (29%) B-GGG3, respectively. The overall upgrading and NOC rates were 11% and 51% for a combined rate of upgrading and/or NOC stage of 53%. In multivariable logistic regression models predicting upgrading, only B-GGG3 was an independent predictor (odds ratio [OR]: 5.29; 95% confidence interval [CI]: 2.21-14.19; p < 0.001). Conversely, 33%-66% (OR: 2.36; 95% CI: 1.42-3.95; p = 0.001) and >66% of positive biopsy cores (OR: 4.85; 95% CI: 2.84-8.42; p < 0.001), as well as B-GGG2 and B-GGG3 were independent predictors for NOC stage (all p ≤ 0.001). CONCLUSIONS: In cT1c-stage patients with high-risk PSA baseline, but low- to intermediate risk B-GGG, the rate of upgrading to GGG4 or GGG5 is low (11%). However, NOC stage is found in the majority (51%) and can be independently predicted with percentage of positive cores at biopsy and B-GGG.

Survival after radical prostatectomy versus radiation therapy in clinical node-positive prostate cancer.

AIM: To compare overall mortality (OM), cancer-specific mortality (CSM), and other cause mortality (OCM) rates between radical prostatectomy (RP) versus radiotherapy (RT) in clinical node-positive (cN1) prostate cancer (PCa). MATERIALS AND METHODS: Within Surveillance, Epidemiology, End Results (SEER) (2004-2016), we identified 4685 cN1 PCa patients, of whom 3589 (76.6%) versus 1096 (24.4%) were treated with RP versus RT. After 1:1 propensity score matching (PSM), Kaplan-Meier plots and Cox regression models tested the effect of RP versus RT on OM, while cumulative incidence plots and competing-risks regression (CRR) models addressed CSM and OCM between RP and RT patients. All analyses were repeated after the inverse probability of treatment weighting (IPTW). For CSM and OCM analyses, the propensity score was used as a covariate in the regression model. RESULTS: Overall, RT patients were older, harbored higher prostate-specific antigen values, higher clinical T and higher Gleason grade groups. PSM resulted in two equally sized groups of 894 RP versus 894 RT patients. After PSM, 5-year OM, CSM, and OCM rates were, respectively, 15.4% versus 25%, 9.3% versus 17%, and 6.1% versus 8% for RP versus RT (all p < 0.001) and yielded respective multivariate hazard ratios (HRs) of 0.63 (0.52-0.78, p < 0.001), 0.66 (0.52-0.86, p < 0.001), 0.71 (0.5-1.0, p = 0.05), all favoring RP. After IPTW, Cox regression models yielded HR of 0.55 (95% confidence interval [CI] = 0.46-0.66) for OM, and CRR yielded HRs of 0.49 (0.34-0.70) and 0.54 (0.36-0.79) for, respectively, CSM and OCM, all favoring RP (all p < 0.001). CONCLUSIONS: RP may hold a CSM advantage over RT in cN1 PCa patients.

Grade and stage misclassification in intermediate unfavorable-risk prostate cancer radiotherapy candidates.

BACKGROUND: We tested for upgrading (Gleason grade group [GGG] ≥ 4) and/or upstaging to non-organ-confined stage ([NOC] ≥ pT3/pN1) in intermediate unfavorable-risk (IU) prostate cancer (PCa) patients treated with radical prostatectomy, since both change the considerations for dose and/or type of radiotherapy (RT) and duration of androgen deprivation therapy (ADT). METHODS: We relied on Surveillance, Epidemiology, and End Results (2010-2015). Proportions of (a) upgrading, (b) upstaging, or (c) upgrading and/or upstaging were tabulated and tested in multivariable logistic regression models. RESULTS: We identified 7269 IU PCa patients. Upgrading was recorded in 479 (6.6%) and upstaging in 2398 (33.0%), for a total of 2616 (36.0%) upgraded and/or upstaged patients, who no longer fulfilled the IU grade and stage definition. Prostate-specific antigen, clinical stage, biopsy GGG, and percentage of positive cores, neither individually nor in multivariable logistic regression models, discriminated between upgraded and/or upstaged patients versus others. CONCLUSIONS: IU PCa patients showed very high (36%) upgrading and/or upstaging proportion. Interestingly, the overwhelming majority of those were upstaged to NOC. Conversely, very few were upgraded to GGG ≥ 4. In consequence, more than one-third of IU PCa patients treated with RT may be exposed to suboptimal dose and/or type of RT and to insufficient duration of ADT, since their true grade and stage corresponded to high-risk PCa definition, instead of IU PCa. Data about magnetic resonance imaging were not available but may potentially help with better stage discrimination.

Contemporary seminal vesicle invasion rates in NCCN high-risk prostate cancer patients.

BACKGROUND: Contemporary seminal vesicle invasion (SVI) rates in National Cancer Comprehensive Network (NCCN) high-risk prostate cancer (PCa) patients are not well known but essential for treatment planning. We examined SVI rates according to individual patient characteristics for purpose of treatment planning. MATERIALS AND METHODS: Within Surveillance, Epidemiology, and End Results (SEER) database (2010-2015), 4975 NCCN high-risk patients were identified. In the development cohort (SEER geographic region of residence: South, North-East, Mid-West, n = 2456), we fitted a multivariable logistic regression model predicting SVI. Its accuracy, calibration, and decision curve analyses (DCAs) were then tested versus previous models within the external validation cohort (SEER geographic region of residence: West, n = 2519). RESULTS: Out of 4975 patients, 28% had SVI. SVI rate ranged from 8% to 89% according to clinical T stage, prostate-specific antigen (PSA), biopsy Gleason Grade Group and percentage of positive biopsy cores. In the development cohort, these variables were independent predictors of SVI. In the external validation cohort, the current model achieved 77.6% accuracy vs 73.7% for Memorial Sloan Kettering Cancer Centre (MSKCC) vs 68.6% for Gallina et al. Calibration was better than for the two alternatives: departures from ideal predictions were 6.0% for the current model vs 9.8% for MSKCC vs 38.5% for Gallina et al. In DCAs, the current model outperformed both alternatives. Finally, different nomogram cutoffs allowed to discriminate between low versus high SVI risk patients. CONCLUSIONS: More than a quarter of NCCN high-risk PCa patients harbored SVI. Since SVI positivity rate varies from 8% to 89%, the currently developed model offers a valuable approach to distinguish between low and high SVI risk patients.

Cancer-specific survival after radical prostatectomy versus external beam radiotherapy in high-risk and very high-risk African American prostate cancer patients.

BACKGROUND: To test for differences in cancer-specific mortality (CSM) rates between radical prostatectomy (RP) vs external beam radiotherapy (EBRT) in National Comprehensive Cancer Network (NCCN) high-risk African American patients, as well as Johns Hopkins University (JHU) high-risk and very high-risk patients. MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2010-2016), we identified 4165 NCCN high-risk patients, of whom 1944 (46.7%) and 2221 (53.3%) patients qualified for JHU high-risk or very high-risk definitions. Of all 4165 patients, 1390 (33.5%) were treated with RP versus 2775 (66.6%) with EBRT. Cumulative incidence plots and competing risks regression models addressed CSM before and after 1:1 propensity score matching between RP and EBRT NCCN high-risk patients. Subsequently, analyses were repeated separately in JHU high-risk and very high-risk subgroups. Finally, all analyses were repeated after landmark analyses were applied. RESULTS: In the NCCN high-risk cohort, 5-year CSM rates for RP versus EBRT were 2.4 versus 5.2%, yielding a multivariable hazard ratio of 0.50 (95% confidence interval [CI] 0.30-0.84, p = 0.009) favoring RP. In JHU very high-risk patients 5-year CSM rates for RP versus EBRT were 3.7 versus 8.4%, respectively, yielding a multivariable hazard ratio of 0.51 (95% CI: 0.28-0.95, p = 0.03) favoring RP. Conversely, in JHU high-risk patients, no significant CSM difference was recorded between RP vs EBRT (5-year CSM rates: 1.3 vs 1.3%; multivariable hazard ratio: 0.55, 95% CI: 0.16-1.90, p = 0.3). Observations were confirmed in propensity score-matched and landmark analyses adjusted cohorts. CONCLUSIONS: In JHU very high-risk African American patients, RP may hold a CSM advantage over EBRT, but not in JHU high-risk African American patients.