Oncological outcomes of pathologically organ-confined,lymph node-positive prostate cancer after radical prostatectomy

BackgroundThe aim of this study was to investigate the impact of lymph-node involvement on oncological outcomes in patients with pathologically organ-confined prostate cancer (pT2 CaP) after radical prostatectomy (RP).MethodsWe retrospectively analyzed 9,631 pT2 CaP patients who underwent RP at a single institution between 1998 and 2018. Kaplan-Meier plots and Cox regression models (CRMs) assessed biochemical recurrence (BCR)-free survival and metastasis-free survival (MFS) according to N-stage. In subgroup analyses of N1 patients, Kaplan-Meier plots and CRMs were stratified according to adjuvant treatment.ResultsOf 9,631 pT2 staged patients, 241 (2.5%) harbored lymph-node metastases after RP (pN1). The median follow-up was 60.8 months. No pT2 N1-staged patient died due to CaP. The 5-year BCR-free survival rates were 54.7 vs. 88.4% in pT2 N1 vs. pT2 N0 patients, respectively (P < 0.001). The 5-year MFS rates were 92.5 vs. 98.9% in pT2 N1 vs. pT2 N0 patients, respectively (P < 0.001). Within pT2 N1 patients, presence of ≥3 positive lymph nodes was an independent risk factor for BCR (hazard ratio [HR] 3.4, P < 0.001) and for metastatic progression (HR 1.7, P = 0.04). Finally, 3-year BCR-free survival was improved in pT2 N1 patients treated with adjuvant radiation therapy (87.1% vs. 63.7% for patients who received other treatment options [P < 0.001]).ConclusionPatients with pathologically organ-confined but lymph node-positive CaP exhibited favorable oncological outcomes after RP. Presence of ≥3 positive LNs predicted higher rates of BCR and metastatic progression. In consequence, in pT2 N1 patients treated with RP with ≥3 positive LNs, adjuvant treatment may be considered.9     

Oncologic outcomes of organ-confined Gleason grade group 4-5 prostate cancer after radical prostatectomy

BackgroundOrgan-confined prostate cancer (CaP) at radical prostatectomy (RP) is associated with good long-term outcomes. However, information for aggressive Gleason organ-confined CaP is scant. To investigate the impact of Gleason grade group (GG) 4-5 on long-term oncologic outcomes after RP.MethodsWithin a high-volume center database we identified patients who harbored organ-confined CaP (pT2) at RP between 1992 and 2017. Only patients with negative surgical margins, without lymph node invasion and without neo- and/or adjuvant androgen deprivation therapy and/or adjuvant radiotherapy were included. Patients with GG1 were excluded. Kaplan-Meier analyses and Cox regression models tested the effect of GG4 and GG5 on biochemical recurrence-free (BFS), metastasis-free (MFS), overall survival (OS) and cancer-specific mortality (CSM) free survival.Results and limitationsOf 10,855 identified pT2 patients, 0.1% (n=81) and 0.1% (n=114) harbored GG4 and GG5, respectively. At 10-years after RP, BFS, MFS, OS and CSM-free rates were 80.3 vs. 68.6 vs. 55.4% (P<0.001), 96.7 vs. 89.9. vs. 83.4% (P<0.001), 93.2 vs. 78.3 vs. 72.6% (P<0.001) and 99.3 vs. 98.0 vs. 82.7% (P<0.001) for GG2 and GG3 vs. GG4 vs. GG5, respectively. In multivariable Cox regression models, GG5 represented an independent predictor for biochemical recurrence (Hazard ratio [HR] 3.00, P<0.001), metastasis (HR 5.01, P<0.001), death (HR 2.72, P<0.01) and cancer-specific death (HR 30.1, P<0.001). Conversely, GG4 represented an independent predictor for death (HR 2.10, P=0.04) and cancer-specific death (HR 6.09, P=0.01) but not for biochemical recurrence and metastasis.ConclusionGG4/5 in organ-confined CaP is rare. But its associated with worse oncologic outcomes after RP, namely biochemical recurrence, metastasis, death and cancer-specific death. Patients with organ-confined GG4/5 and negative margins should be closely followed and may be candidates for risk stratification by genomic markers.     

Impact of adjuvant androgen deprivation therapy after radical prostatectomy on the survival of patients with pathological T3b prostate cancer

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? Adjuvant hormonal therapy is known to improve cancer specific survival in prostate cancer patients with lymph node positive disease. This study suggests that surgically treated prostate cancer patients with seminal vesical invasion (pT3b) may have improved cancer specific survival if treated with adjuvant androgen deprivation therapy, similar to lymph node positive patients.

OBJECTIVE

To determine the impact of adjuvant androgen deprivation therapy (ADT) on survival in patients with seminal vesicle invasion (pT3b) at radical prostatectomy.

PATIENTS AND METHODS

We reviewed 12 115 patients who underwent radical prostatectomy between 1987 and 2002 to identify patients with pT3bN0 prostate cancer who received adjuvant ADT (n= 191). These patients were matched by clinical and pathological variables to a group of patients with pT3b prostate cancer who did not receive adjuvant ADT. Median postoperative follow‐up was 10 years. Clinical endpoints included biochemical progression‐free survival (BPFS), local recurrence‐free survival (LRFS), systemic progression‐free survival (SPFS), cancer‐specific survival (CSS) and overall survival.

RESULTS

Patients who underwent adjuvant ADT experienced improved 10‐year BPFS (60% vs 16%, P < 0.001), LRFS (87% vs 76%, P= 0.002), SPFS (91% vs 78%, P= 0.004) and CSS (94% vs 87%, P= 0.037). Overall survival was not significantly different between groups (75% vs 69%, P= 0.12). Both luteinizing hormone‐releasing hormone agonists (hazard ratio, 0.26; 95% CI, 0.15–0.46; P < 0.001) and bilateral orchiectomy (hazard ratio, 0.13; 95% CI, 0.06–0.31; P < 0.001) improved BPFS. When stratified by type of ADT (hormonal therapy vs orchiectomy), there was no difference in survival outcomes.

CONCLUSIONS

Adjuvant ADT improves local, and systemic control after radical prostatectomy for pT3b prostate cancer. There is no difference in survival between patients receiving medical hormonal therapy vs patients undergoing orchiectomy. Given the lack of improvement in overall survival, continued investigation is needed to identify the cohort of pT3b patients at highest risk for cancer progression and therefore most likely to benefit from a multimodal treatment approach.     

Long-term cancer control after radical prostatectomy and bilateral pelvic lymph node dissection for pT3bN0M0 prostate cancer in the prostate-specific antigen era

ObjectivesWe evaluated long-term cancer control outcomes of radical prostatectomy and bilateral pelvic lymph node dissection (RP) for pT3bN0M0 prostate cancer in the era of prostate-specific antigen (PSA) screening.Materials and methodsA retrospective analysis of prospectively collected data from the University of Southern California Prostate Cancer Database was performed. Between 1987 and 2008, 229 men underwent open RP for pT3bN0M0 prostate cancer. The cohort was divided into early (1987–1997) and contemporary (1998–2008) PSA eras. The Kaplan-Meier method and Cox proportional regression models were used to analyze clinical recurrence (CR) and biochemical recurrence (BCR).ResultsThe median follow-up duration was 14.5 years (range, 0.2–21.1 y). The predicted 10-year freedom from CR and BCR rates for men treated in the early and contemporary PSA eras were 73% and 95% (Log-rank P = 0.001) and 65% and 73% (Log-rank P = 0.055), respectively. Multivariable analysis showed that pathologic Gleason grade 8–10 (CR: hazard ratio [HR] = 5.11; 95% confidence interval [CI] = 1.72–15.20; P = 0.003; BCR: HR = 3.47; 95% CI = 1.60–7.48; P = 0.002) and contemporary PSA era (CR: HR = 0.15; 95% CI = 0.06–0.41; P<0.001; BCR: HR = 0.49; 95% CI = 0.28–0.86; P = 0.013) were independently associated with cancer control. Adjuvant radiation therapy and positive surgical margins were not independently associated with outcomes.ConclusionsRP conferred long-term cancer control in men with pT3bN0M0 prostate cancer treated in the PSA era. Pathologic Gleason grade 8–10 and treatment in the early PSA era were independently associated with poorer cancer control outcomes.     

Prognostic significance of positive surgical margins after radical prostatectomy among pT2 and pT3a prostate cancer

ObjectiveTo investigate the prognostic significance of positive surgical margins (PSM)s among patients who underwent radical prostatectomy (RP) for pT2 and pT3a prostate cancer.Patients and methodsWe reviewed the records of 658 patients who were revealed to have pT2 and pT3a prostate cancer after undergoing RP without neoadjuvant or adjuvant treatment. For our analysis, patients were subgrouped as the following: group 1: 406 (61.7%) with negative surgical margins (NSM)s and no extracapsular extension of tumor (ECE); group 2: 99 (15.0%) with PSMs and no ECE; group 3: 63 (9.6%) with NSMs and ECE; and group 4: 90 (13.7%) with PSMs and ECE. The effects of various variables on biochemical recurrence (BCR)-free survival were assessed via uni- and multivariate analyses.ResultsDuring median follow-up of 36 months, group 1 had significantly higher BCR-free survival compared with the other 3 groups (P < 0.001). However, no significant differences in BCR-free survivals were observed among the group 2, 3, and 4 (all P > 0.05). In multivariate analysis, PSM (P = 0.009) was observed to be significantly associated with BCR-free survival among groups 1 and 2 combined. Among groups 3 and 4, pathologic Gleason score (P = 0.002), but not PSM (P = 0.668), was the only significant predictor for BCR-free survival in multivariate analysis.ConclusionsAccording to our results, PSM is significantly associated with biochemical outcome after RP in pT2 prostate cancer. Meanwhile, patients with pT2 tumor and PSM appear to have comparable biochemical outcome compared with those with stage pT3a tumor independent of their marginal status.     

A novel nomogram predicting lymph node invasion among patients with prostate cancer: The importance of extracapsular extension at multiparametric magnetic resonance imaging

PurposeTo develop a novel risk tool that allows the prediction of lymph node invasion (LNI) among patients with prostate cancer (PCa) treated with robot-assisted radical prostatectomy (RARP) and extended pelvic lymph node dissection (ePLND).MethodsWe retrospectively identified 742 patients treated with RARP + ePLND at a single center between 2012 and 2018. All patients underwent multiparametric magnetic resonance imaging (mpMRI) and were diagnosed with targeted biopsies. First, the nomogram published by Briganti et al. was validated in our cohort. Second, three novel multivariable logistic regression models predicting LNI were developed: (1) a complete model fitted with PSA, ISUP grade groups, percentage of positive cores (PCP), extracapsular extension (ECE), and Prostate Imaging Reporting and Data System (PI-RADS) score; (2) a simplified model where ECE score was not included (model 1); and (3) a simplified model where PI-RADS score was not included (model 2). The predictive accuracy of the models was assessed with the receiver operating characteristic-derived area under the curve (AUC). Calibration plots and decision curve analyses were used.ResultsOverall, 149 patients (20%) had LNI. In multivariable logistic regression models, PSA (OR: 1.03; P= 0.001), ISUP grade groups (OR: 1.33; P= 0.001), PCP (OR: 1.01; P= 0.01), and ECE score (ECE 4 vs. 3 OR: 2.99; ECE 5 vs. 3 OR: 6.97; P< 0.001) were associated with higher rates of LNI. The AUC of the Briganti et al. model was 74%. Conversely, the AUC of model 1 vs. model 2 vs. complete model was, respectively, 78% vs. 81% vs. 81%. Simplified model 1 (ECE score only) was then chosen as the best performing model. A nomogram to calculate the individual probability of LNI, based on model 1 was created. Setting our cut-off at 5% we missed only 2.6% of LNI patients.ConclusionsWe developed a novel nomogram that combines PSA, ISUP grade groups, PCP, and mpMRI-derived ECE score to predict the probability of LNI at final pathology in RARP candidates. The application of a nomogram derived cut-off of 5% allows to avoid a consistent number of ePLND procedures, missing only 2.6% of LNI patients. External validation of our model is needed.     

Degree of hydronephrosis predicts adverse pathological features and worse oncologic outcomes in patients with high-grade urothelial carcinoma of the upper urinary tract

ObjectiveTo evaluate degree of hydronephrosis (HN) as a surrogate for adverse pathological features and oncologic outcomes in patients with high-grade (HG) and low-grade (LG) upper tract urothelial carcinomas (UTUCs).MethodsWe retrospectively reviewed 141 patients with localized UTUCs that underwent extirpative surgery at a tertiary referral center. Preoperative imaging was used to evaluate presence and degree of ipsilateral HN. We evaluated degree of HN (none/mild vs. moderate/severe), pathological findings, and oncologic outcomes.ResultsHG UTUC was present in 113 (80%) patients, muscle-invasive disease (≥pT2) in 49 (35%), and non–organ-confined disease (≥pT3) in 41 (29%). At a median follow-up of 34 months, 49 (35%) patients experienced intravesical recurrence, 28 (20%) developed local/systemic recurrence, and 24 (17%) died of UTUC. HN was graded as none/mild in 77 (55%) patients and moderate/severe in 64 (45%). In patients with HG UTUC, but not LG, degree of HN was associated with advanced pathological stage (P<0.001), positive lymph nodes (P = 0.01), local/systemic recurrence-free survival (hazard ratio [HR] = 5.5, P = 0.02), and cancer-specific survival (HR = 5.2, P = 0.02). On multivariable analysis of preoperative factors, degree of HN in patients with HG UTUC was associated with muscle invasion (HR = 9.3; 95% CI: 3.08–28.32; P<0.001), non–organ-confined disease (HR = 4.5; 95% CI: 1.66–12.06; P = 0.003), local/systemic recurrence-free survival (HR = 2.5; 95% CI: 1.07–5.64; P = 0.04), and cancer-specific survival (HR = 2.6; 95% CI: 1.05–6.22; P = 0.04).ConclusionsDegree of HN can serve as a surrogate for advanced disease and predict worse oncologic outcomes in HG UTUC. Degree of HN was not predictive of intravesical or local/systemic recurrence in LG UTUC.     

Clinically node-positive (cN+) urothelial carcinoma of the bladder treated with chemotherapy and radical cystectomy: Clinical outcomes and development of a postoperative risk stratification model

Introduction and objectiveAlthough node-positive (cN+) bladder cancer is considered Stage IV disease, a subset of patients is treated with chemotherapy and consolidative radical cystectomy (RC). We examined the clinical outcomes of such patients and developed a risk prediction model to facilitate risk-stratification and management.MethodsWe identified adult patients with cTany cN1-3 M0 urothelial carcinoma of the bladder treated with chemotherapy followed by RC from 2006 to 2013 in the NCDB. The associations of clinicopathologic features with overall survival (OS) were evaluated using Cox regression, and a simplified risk score was developed.ResultsA total of 491 patients received chemotherapy followed by RC. Median number of lymph nodes removed was 16 (interquartile range 9–25). At RC, 10% of patients were ypT0, and 35% were ypN0. Over a median follow-up of 18.7 months, 160 patients died of any cause. 1-, 5-, and 8-year OS were 69%, 34%, and 29%, respectively. On multivariable analysis, pT stage (hazard ratio [HR] 2.18; P = 0.003 for pT3, HR 2.65; P < 0.001 for pT4 vs. <pT2) and pN stage (HR 1.77; P = 0.02 for pN1; HR 2.58; P < 0.001 for pN2; HR 5.09; P < 0.001 for pN3 vs. pN0) were independently associated with worse OS. A risk score was developed based on pT and pN stages, with 5-year OS of 59%, 24%, and 10% for risk score groups of 0-1, 2, and ≥3 points.ConclusionsSurvival for patients with cN+ bladder cancer treated with chemotherapy and RC is highly variable, ranging from 10% to 59% at 5 years. A risk score can facilitate postoperative risk-stratification and selection of patients for adjuvant therapy.     

Multi-institutional validation of the ability of preoperative hydronephrosis to predict advanced pathologic tumor stage in upper-tract urothelial carcinoma

ObjectiveThe presence of hydronephrosis (HN) has been implicated as a predictor of poor outcomes for patients diagnosed with bladder cancer. Small, single institution preliminary reports suggest a similar negative relationship may exist for upper-tract urothelial carcinoma (UTUC). Herein, we attempt to validate the prognostic value of preoperative HN in a large, multi-institutional cohort of UTUC patients.Materials and methodsData on 469 patients with localized UTUC from 5 tertiary referral centers who underwent a radical nephroureterectomy (91%) or distal ureterectomy (9%) without neoadjuvant chemotherapy were integrated into a relational database. Preoperative HN data, including presence vs. absence and high vs. low grade, were available in 408 patients. The association of HN with pathologic features was evaluated.ResultsA total of 254 men and 154 women with a median age of 69 years (IQR 15) were analyzed. Overall, 192 patients (47%) had ≥pT2 disease, 145 (36%) had non-organ-confined (NOC) cancers (≥pT3 and/or positive lymph nodes), and 298 (73%) had high grade UTUC on final pathology. Forty-six percent of patients had tumors in the renal pelvis, 27% in the ureter, and 27% in both locations. Preoperatively, 223 patients (55%) were noted to have ipsilateral HN (39% low grade and 61% high grade). Hydronephrosis was associated with ≥pT2 stage (P < 0.001), NOC disease (P < 0.001), and high grade cancers (P = 0.04). On multivariate analysis adjusting for gender, age, and tumor location, HN was an independent predictor of muscle invasive (HR 7.4, P < 0.001), NOC (HR 5.5, P < 0.001), and high pathologic grade (HR 1.6, P = 0.03) UTUC disease.ConclusionThe presence of preoperative HN was associated with advanced stage UTUC. This readily available imaging modality may improve preoperative risk stratification for UTUC patients thereby guiding use of endoscopic versus extirpative surgery as well as the need for neoadjuvant chemotherapy regimens.     

Prognostic markers in invasive bladder cancer: FGFR3 mutation status versus P53 and KI-67 expression: a multi-center,multi-laboratory analysis in 1058 radical cystectomy patients

ObjectivesTo determine the association between the FGFR3 mutation status and immuno-histochemistry (IHC) markers (p53 and Ki-67) in invasive bladder cancer (BC), and to analyze their prognostic value in a multicenter, multi-laboratory radical cystectomy (RC) cohort.Patients and methodsWe included 1058 cN0M0, chemotherapy-naive BC patients who underwent RC with pelvic lymph-node dissection at 8 hospitals. The specimens were reviewed by uro-pathologists. Mutations in the FGFR3 gene were examined using PCR-SNaPshot; p53 and Ki-67 expression were determined by standard IHC. FGFR3 mutation status as well as p53 (cut-off>10%) and Ki-67 (cut-off>20%) expression were correlated to clinicopathological parameters and disease specific survival (DSS).ResultspT-stage was <pT2 in 80, pT2 in 266, pT3 in 513 and pT4 in 199 patients, respectively. Cancer-positive nodes were found in 410 (39%) patients. An FGFR3 mutation was detected in 107 (10%) and aberrant p53 and Ki-67 expression in 718 (68%) and 581(55%) tumors, respectively. The FGFR3 mutation was associated with lower pT-stage (P<0.001), lower grade (P<0.001), pN0 (P=0.001) and prolonged DSS (P<0.001). Aberrant Ki-67 and p53 expression were associated with higher pT-stage and G3-tumors, but not with pN-stage or worse DSS, even if these IHC-biomarkers were combined (P=0.81). Significant predictors for DSS in multivariable analysis were pT-stage (HR1.5, 95%CI:1.3-1.6; P<0.001), lympho-vascular invasion (LVI) (HR1.4, 95%CI:1.2-1.7; P=0.001), pN-stage (HR1.9, 95%CI:1.6-2.4; P<0.001) and FGFR3 mutation status (HR1.6, 95%CI:1.1-2.2; P=0.011).ConclusionThe FGFR3 mutation selectively identified patients with favorable BC at RC while p53 and Ki-67 were only associated with adverse tumor characteristics. Our results suggest that, besides tumor-stage, nodal-status and LVI, the oncogenic FGFR3 mutation may represent a valuable tool to guide adjuvant treatment and follow-up strategies after RC.     

Preoperative characteristics of men with unfavorable high-Gleason prostate cancer at radical prostatectomy

IntroductionSome men with Gleason sum 8–10 prostate cancer (PC) at RP have favorable outcomes: Biochemical recurrence free (BFS) and prostate cancer-specific survival (CSS) are improved for such men with pT2 or pT3a disease compared with pT3b or N1 disease at radical prostatectomy (RP). We examine biopsy characteristics of men with high-grade PC at RP to better select those who may benefit from surgery.Materials and MethodsA total of 1,174 men from our Institutional Database (1982–2010) had Gleason 8–10 cancer at RP. Their demographic and prostate biopsy characteristics were compared among those with disease defined as favorable (pT2 or pT3a) vs. unfavorable (pT3b or N1). Logistic regression was used to determine predictors of unfavorable disease. Kaplan-Meier analysis was used to determine survival outcomes.ResultsBiopsy data were available for 1,157 men (median cores 12 [2–20]); 779 (66.4%) favorable, 394 (33.6%) unfavorable; 102 (8.7%), 515 (44.1%), and 552 (47.2%) were low, intermediate, and high-risk. For favorable and unfavorable cases, 10-year BFS was 40.0% and 5.7% (P < 0.001) and CSS was 84.9% and 60.3% (P < 0.001). Multivariate logistic regression revealed that PSA ≥ 20 and perineural invasion (PNI) at biopsy increased the likelihood of unfavorable, high-grade disease. Considering PSA ≥ 20 and PNI as adverse features, 23.7%, 40.1%, and 71.4% of patients with none, 1, or 2 adverse features had unfavorable, high-Gleason PC (P < 0.001).ConclusionsHigh-Gleason PC was not uniformly associated with poor outcomes after RP, though men with unfavorable (pT3b/N1) disease fared poorly. Preoperative predictors of high-Gleason, unfavorable disease in a cohort of predominantly intermediate and high-risk patients were PSA ≥ 20 and PNI.     

Local recurrence following complete radiologic response in patients treated with transarterial chemoembolization for hepatocellular carcinoma

PurposeThe purpose of this study was to determine the local progression rate and identify factors that may predict local progression, in patients who achieve a complete response (CR) radiologically after undergoing transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).Materials and methodsOne-hundred-forty-seven patients, who achieved CR of 224 HCCs after TACE, were retrospectively reviewed. There were 109 men and 38 women with a mean age of 61.6 ± 6.8 (SD) years (range: 45.4–86.9 years). Logistic mixed-effects and Cox regression models were used to evaluate associations between clinical factors and local progression.ResultsA total of 75 patients (75/147; 51%) and 99 (99/224,44.2%) lesions showed local progression at a median of 289.5 days (Q1: 125, Q3: 452; range: 51–2245 days). Pre-treatment, international normalization ratio (INR) (1.17 ± 0.15 [SD] vs. 1.25 ± 0.16 [SD]; P <0.001), model for end-stage liver disease (9.4 ± 2.6 [SD] vs. 10.6 ± 3.2 [SD]; P = 0.010) and Child-Pugh score (6 ± 1 [SD] vs. 6.4 ± 1.3 [SD]; P = 0.012) were significantly lower while albumin serum level (3.4 ± 0.62 [SD] vs. 3.22 ± 0.52 [SD]; P = 0.033) was significantly greater in those who showed local progression as compared to those who did not. In terms of local-recurrence free survival, the number of TACE treatments (hazard ratio [HR]: 2.05 [95% CI: 1.57–2.67]; P<0.001), INR (HR: 0.13 [95% CI: 0.03–0.61]; P = 0.010) and type of TACE (P = 0.003) were significant. Patients with local progression on any tumor did not differ from those who did in terms of overall survival (P = 0.072), however, were less likely to be transplanted (20/75, 26.7%) than those who did not (33/72; 36.1%) (P = 0.016).ConclusionA significant number of patients who achieve CR of HCC after TACE have local progression. This emphasizes the importance of long-term follow up.     

Primary Ta high grade bladder tumors: Determination of the risk of progression

PurposeTaG3 bladder cancer is an under-investigated disease and because of its rarity it is commonly studies together with T1G3 disease. We sought to exclusively study TaG3 disease and to determine the factors associated with disease progression.Material and methodWe retrospectively studied patients with primary TaG3 bladder cancer. Progression to ≥pT1 and pT2 were analyzed using Cox and competing-risk regression analyses.ResultsOf 3,505 consecutive patients with nonmuscle invasive bladder cancer, 285 patients had primary TaG3 without concomitant carcinoma in-situ. Progression to ≥pT1 occurred in 21 patients (7.4%). In a multivariable competing-risk regression analysis, intravesical Bacillus Calmette-Guerin (BCG) was significantly associated with a lower risk of progression to ≥pT1 (HR 0.23, 95%CI 0.08–0.64, P = 0.005). Recurrence in the first year of diagnosis was significantly associated with an increased risk of stage progression to ≥pT1 (HR 7.81, 95%CI 2.50–24.44, P < 0.001). Progression to ≥T2 was observed in 9 patients (3.2%). In univariable competing-risk regression analyses, intravesical BCG was significantly associated with a lower risk of progression to ≥pT2 (HR 0.11, 95%CI 0.04–0.47, P = 0.003). On the other hand, recurrence in the first year of diagnosis was significantly associated with an increased risk of stage progression to ≥T2 (HR 7.12, 95%CI 1.50–33.77, P = 0.013). In a subgroup of 199 patients who were treated with BCG, there was no statistically significant association between tumor recurrence in the 1^st year of diagnosis and stage progression to ≥pT1 (P = 0.14) or ≥pT2(P = 0.19).ConclusionPatients with TaG3 bladder cancer are considered high risk but if appropriately treated with BCG that risk is considerably mitigated. Our data support that TaG3 without concomitant carcinoma in-situ should not be considered as aggressive as T1G3 as it has a lower risk of progression to muscle-invasive bladder cancer. Recurrence in the first year after diagnosis is the strongest predictor of progression to muscle-invasive bladder cancer.     

Black race may be associated with worse overall survival in renal cell carcinoma patients

ObjectiveTo examine socio-demographic and treatment variables in an attempt to identify factors associated with survival differences between black and white patients with renal cell carcinoma (RCC).Patients and MethodsWe identified 79,618 white and 10,604 black patients diagnosed with RCC in the National Cancer Database. We compared the distribution of socio-demographic, presentation and treatment variables between Blacks and Whites and then utilized a multivariable cox proportion hazards regression model to evaluate the contribution of differences in these variables to disparities in overall survival (OS).ResultsBlack patients were younger (60 vs. 63 years, P< 0.001) and with a lower stage (12.0% vs. 18.8% Stage III–IV P< 0.001). Blacks presented with a higher Charlson-Deyo score (P< 0.001), lower income (P< 0.001), lower education (P< 0.001) and were less likely to receive radical nephrectomy and systemic therapy for stage IV RCC (29.9% vs. 38.8%, P< 0.001). Unadjusted OS was lower for Whites (5-year survival 79% for Blacks and 77% for Whites). However, OS was lower for Blacks when adjusted for all variables (5-year survival 89% for Blacks and 93% for Whites). On multivariable analysis, black race was independently associated with worse OS, HR: 1.09 (95% confidence interval: 1.03, 1.14, P= 0.002). A sensitivity analysis including patients with complete data on tumor grade confirmed our results.ConclusionOur study indicates that black patients present at a younger age and with lower stage RCC, but have worse OS. Blacks experienced disparities in socio-demographic characteristics, clinical presentation, treatment-related factors, and had an independently increased hazard of death.     

Presence of positive surgical margin in patients with organ-confined prostate cancer equals to extracapsular extension negative surgical margin. A plea for TNM staging system reclassification

BackgroundTo test the hypothesis that patients with pT2 and positive surgical margins (SM) have a similar biochemical-recurrence (BCR) risk to patients with pT3a, and negative SM. Moreover, we examined the effect of incorporating positive SM as a higher stage on the discrimination accuracy of the current TNM staging system.Materials and methodsWe evaluated 1,503 prostate cancer patients treated with radical prostatectomy, between 1998 and 2010. Only individuals with pT2N0 or pT3aN0, without neoadjuvant and/or adjuvant therapy, were included. Cox regression analyses tested the relationship between SM status (negative [R0] vs. positive [R1]) and BCR rate, after stratification according to T stage. Predictive accuracy of the current T stage and of a novel T stage, which consider positive SM as a higher stage, was quantified with Harrell's concordance index.ResultsPositive SM rate was 20.3%. The 5-year BCR rates were 96%, 82%, 78%, and 62% for patients with, respectively, pT2R0, pT2R1, pT3aR0, and pT3a1 (all P ≤ 0.03). In multivariable analyses, the BCR rate was 3.6-, 2.5-, and 6.0-fold higher (all P < 0.001) in patients with, respectively, pT2R1, pT3aR0, and pT3aR1 stage relative to patients with pT2R0 stage. The maximum univariable (14.1%) and multivariable (6.9%) discrimination accuracy gains were observed, when tumor stage was stratified into pT2R0 vs. pT2R1/pT3R0 vs. pT3R1.ConclusionsThe presence of positive SM at radical prostatectomy (RP) specimen substantially increases the BCR risk. Patients with pT2R1 have similar BCR risk to patients with pT3aR0. Considering these patients as 1 category substantially improves the discrimination accuracy of the current TNM staging system.     

Validation of tertiary Gleason pattern 5 in Gleason score 7 prostate cancer as an independent predictor of biochemical recurrence and development of a prognostic model

ObjectiveTo validate the biological and prognostic value of tertiary Gleason pattern 5 (TGP5) in patients with Gleason score 7 (GS 7) prostate cancer (PCa) and to develop a prognostic model to identify the high-risk group of patients with TGP5.Material and methodsWe retrospectively reviewed the data from 4,146 patients with localized (pT2–3 N0 M0) GS 7 PCa treated by radical prostatectomy (RP) without adjuvant therapy. The primary end point was biochemical recurrence (BCR), and the secondary one was to build a bootstrap-corrected multivariable Cox model.ResultsOf the 4,146 patients, 416 (10%) had a TPG5 in the RP specimen. TGP5 was associated with BCR in both univariable and multivariable analyses that adjusted for the effects of standard pathological features (P<0.001). A prognostic model based on preoperative prostate-specific antigen levels (<10 vs.≥10 ng/ml), primary and secondary Gleason pattern (3+4 vs. 4+3), pathological tumor category (pT2/pT3a vs. pT3b), and surgical margin status (R0 vs. R+) stratified patients with a discrimination of 72.2%. Patients in the low-risk group had a 5-year BCR-free survival rate of 76.3% compared with only 18.5% for those in the high-risk group (P<0.001).ConclusionsKnowledge of TGP5 improves our prognostication of patients with GS 7 PCa treated with RP. We developed a statistical tool to help identify the patients with TGP5 who are at the highest risk of BCR after RP, thereby helping with the clinical decision making regarding adjuvant trials and follow-up scheduling.     

Gender-specific differences in cancer-specific survival after radical cystectomy for patients with urothelial carcinoma of the urinary bladder in pathologic tumor stage T4a

BackgroundBladder cancer (UCB) staged pT4a show heterogeneous outcome after radical cystectomy (RC). No risk model has been established to date. Despite gender-specific differences, no comparative studies exist for this tumor stage.Materials and methodsCancer-specific survival (CSS) of 245 UCB patients without neoadjuvant chemotherapy staged pT4a, pN0-2, M0 after RC were analyzed in a retrospective multi-center study. Seventeen patients were excluded from further analysis due to carcinoma in situ (CIS) of the prostatic urethra and/or positive surgical margins. Average follow-up period was 30 months (IQR: 14–45). The influence of different clinical and histopathologic variables on CSS was determined through uni- and multivariate Cox regression analyses. Two risk groups were generated using factors with independent effect in multivariate models. Internal validity of the prediction model was evaluated by bootstrapping.ResultsEighty-four percent of the patients (n = 192) were male; 72% (n = 165) showed lymphovascular invasion (LVI). The 5-year CSS rate was 31%, and significantly different between male and female (35% vs. 15%, P = 0.003). Multivariate Cox regression modeling, female gender (HR = 1.83, P = 0.008), LVI (HR = 1.92, P = 0.005), and absence of adjuvant chemotherapy (HR = 0.61, P = 0.020) significantly worsened CSS. Two risk groups were generated using these 3 criteria, which differed significantly between each other in CSS (5-year-CSS: 46% vs. 12%, P < 0.001). The c-index value of the risk model was 0.61 (95% CI: 0.53–0.68, P < 0.001).ConclusionsPrognosis in UCB staged pT4a is heterogeneous. Female gender and LVI are adverse factors. Adjuvant chemotherapy seems to improve outcome. The present analysis establishes the first risk model for this demanding tumor stage.     

Clinical significance of fatty liver disease induced by tamoxifen and toremifene in breast cancer patients

Background and AimThe aim of this study was to identify the effect of selective estrogen receptor modulator (SERM) on non-alcoholic fatty liver disease (NAFLD) in Asian women.MethodsWe retrospectively evaluated fatty liver development and/or serum alanine aminotransferase (ALT) elevation during SERM treatment in 1061 women who were diagnosed and treated with breast cancer in 2005 at Asan Medical Center.Results45 of 618 SERM-treated patients with normal ALT at baseline experienced ALT elevation during SERM treatment. Among the 112 SERM-treated patients who underwent liver imaging test, fatty liver was observed in 47 and both fatty liver and ALT elevation developed in 16 of 102 SERM-treated patients with normal baseline ALT. The cumulative rates of ALT elevation (10.7 vs. 4.3%; P = 0.002), fatty liver (48.5 vs. 20.9%; P < 0.001), and both fatty liver and ALT elevation (17.7 vs. 7.1%; P = 0.02) at 60 months were significantly higher in the SERM group than non-SERM group. By multivariate analysis, SERM treatment increased the risk of ALT elevation (hazard ratio [HR], 2.20; P = 0.01), fatty liver development (HR, 3.59; P < 0.001), and both fatty liver and ALT elevation (HR, 4.98; P = 0.01). After discontinuation of SERM, elevated serum ALT normalized in 39 (92.9%) and there were no instances of liver-related death or progression to liver cirrhosis in patients who experienced fatty liver or ALT elevation.ConclusionsAlthough SERM treatment is significantly associated with NAFLD in Asian women, considering the tolerability and reversibility of NAFLD induced by SERM, it can be continued with liver function monitoring in relevant patients.     

Assessing pentafecta achievement after robot-assisted radical cystectomy and its association with surgical experience: Results from a high-volume institution

ObjectivesRadical cystectomy (RC) represents the gold standard treatment for high-risk bladder cancer. Despite evidence suggesting that surgical experience correlates with perioperative and oncologic outcomes of robot-assisted RC (RARC), validated tools to assess its quality objectively are lacking. We aimed to evaluate the impact of RC-Pentafecta (absence of early major complications, absence of urinary diversion related sequelae at ≤12 months, absence of soft tissue surgical margins, ≥16 lymph nodes at final pathology and absence of clinical recurrence at ≤12 months) on oncological outcomes and the role of surgical experience on its achievement.Materials and methodsWe retrospectively evaluated 366 patients undergoing RARC with intracorporeal urinary diversion in a single tertiary centre with a minimum of 1 year follow-up. Surgeries were performed using the DaVinci Xi system according to a previously described technique. Kaplan-Meier curves were used to investigate 5-years overall survival and cancer specific mortality-free survival (CSS) according to RC-Pentafecta achievement. Multivariable Cox's regressions were performed to evaluate the impact of RC-Pentafecta on overall mortality. Multivariable logistic regressions were performed to explore the effect of surgical experience on RC-pentafecta achievement. Locally weighted scatterplot smoother function was used to graphically explore this relationship.ResultsPatients achieving RC-Pentafecta showed higher 5-year overall survival (71.8% vs. 59.6%, P < 0.001) and CSS (84% vs. 71%, P < 0.001) when compared with patients not achieving it. At multivariable Cox's regression, RC-Pentafecta achievement (HR 0.57, P = 0.03), positive surgical margins (HR 2.48, P = 0.002), pN+ (HR 2.23, P = 0.002), pT≥3 (HR 1.71, P = 0.04) and current smoking status (HR 2.4, P = 0.006) were significant predictors of overall mortality. At multivariable logistic regression surgical experience (OR 1.2, P < 0.001), age (OR 0.93, P = 0.04), previous prostate surgery (OR 0.7, P = 0.02) and pT≥3 (OR 0.8, P = 0.03) were independent predictors of RC-Pentafecta achievement. A linear relationship between surgical experience and RC-Pentafecta achievement, without reaching a plateau, was observed.ConclusionsRC-Pentafecta is a valuable tool to assess surgical quality of RARC and the experience of the center where the surgery is performed and may be used to identify “referral” centers for treatment of high-risk bladder cancer.     

Optimal timing of early versus delayed adjuvant radiotherapy following radical prostatectomy for locally advanced prostate cancer

ObjectivesAlthough post–radical prostatectomy (RP) adjuvant radiation therapy (ART) benefits disease that is staged as pT3 or higher, the optimal ART timing remains unknown. Our objective is to characterize the outcomes and optimal timing of early vs. delayed ART.Materials and methodsFrom the Surveillance, Epidemiology and End Results-Medicare data from 1995 to 2007, we identified 963 men with pT3N0 disease receiving early (<4 mo after RP, n = 419) vs. delayed (4–12 mo after RP, n = 544) ART after RP. Utilizing propensity score methods, we compared overall mortality, prostate cancer–specific mortality (PCSM), bone-related events (BRE), salvage hormonal therapy utilization, and intervention for urethral stricture. We then used the maximal statistic approach to determine at what time post-RP ART had the most significant effect on outcomes of interest in men with pT3N0 disease.ResultsWhen compared with delayed ART in men with pT3 disease, early ART was associated with improved PCSM (0.47 vs. 1.02 events per 100 person-years; P = 0.038) and less salvage hormonal therapy (2.88 vs. 4.59 events per 100 person-years; P = 0.001). Delaying ART beyond 5 months is associated with worse PCSM (hazard ratio [HR] 2.3; P = 0.020), beyond 3 months is associated with more BRE (HR 1.6; P = 0.025), and beyond 4 months is associated higher rates of salvage hormonal therapy (HR 1.6; P = 0.002). ART performed after 9 months was associated with fewer urethral strictures (HR 0.6; P = 0.042).ConclusionInitiating ART less than 5 months after RP for pT3 is associated with improved PCSM. Early ART is also associated with fewer BRE and less use of salvage hormonal therapy if administered earlier than 3 and 4 months after RP, respectively. However, ART administered later than 9 months after RP is associated with fewer urethral strictures. Our population-based findings complement randomized trials designed with fixed ART timing.