Analysis of clinical characteristics, treatment patterns, and outcome of patients with bilateral testicular germ cell tumors.

INTRODUCTION: Bilateral testicular germ cell tumor (BGCT) is a rare disease, occasionally considered to be more aggressive than unilateral germ cell tumors (GCT) in some reports. Among BGCT, a synchronous disease might be diagnosed at a higher stage than a metachronous disease, resulting in lower cancer-specific survival. Hence, our study aimed to perform a comparative analysis between unilateral testicular GCT, bilateral synchronous GCT, and bilateral metachronous GCT, aiming to verify the possibility that BGCT is diagnosed with a higher stage and may require more aggressive management. MATERIAL AND METHODS: In our multicenter retrospective study we reviewed medical records of 40 patients with BGCT (24 metachronous and 16 synchronous). Clinical characteristics, pathological features of the primary and secondary tumors, adjuvant treatments (chemotherapy and radiotherapy)and sperm quality were evaluated as well as cancer-specific survival and overall survival. A cohort of one-to-one matched patients with unilateral GCT were used to determine risk factors for developing BGCT. RESULTS: Patients with BGCT were slightly younger compared to those with unilateral GCT and had more advanced disease. Despite similar T-stage distribution between the two groups, nodal involvement was nearly twofold more frequent in patients with BGCT disease (42% vs 22%, p = 0.056). Additionally, although similar histological subtypes distribution at presentation among the two groups, the synchronous disease was diagnosed with a higher local T-stage (OR = 3.4), higher proportions of patients with elevated serum BHCG levels, and more frequent nodal involvement (OR = 2.2). This was later translated into an 18% higher disease-specific mortality rate. The median time to develop a contralateral tumor was 92 months. Pathological local T-stage (T2-T3) of the primary tumor predicted a shorter time interval to a diagnosis of a second contralateral tumor (HR 0.92, P < 0.05). CONCLUSION: BGCT presents at a younger age and potentially with more advanced disease. Synchronous BGCT is diagnosed at a later stage compared to metachronous BGCT and has higher disease-specific mortality. Metachronous tumors might have a long time interval for the development of a contralateral neoplasm. The main predictor of developing an early metachronous disease is a high primary T stage.

Association between PSA density and pathologically significant prostate cancer: The impact of prostate volume.

BACKGROUND: The early diagnosis of prostate cancer (PCa) is mainly based on prostate-specific antigen (PSA) blood levels and digital rectal examination. However, this approach may result in a high rate of negative biopsies and increased detection of clinically insignificant PCa (CS-PCa). An important prognostic biomarker, PSA density (PSA-D) demonstrated improved performance in PCa detection compared to PSA. The relationship between prostate volume and the prognostic accuracy of PSA-D remains mostly unclear. The aim of our study is to investigate the PSA-D predictive value of CS-PCa detection at different prostate volumes. METHODS: Using our local radical prostatectomy registry, patients were divided into three prostate size subgroups based on preoperative sonographic prostate volume assessment: less than 50, 50-75, and more than 75 cc. Patients' and PCa characteristics were recorded, including age, body mass index, PSA at diagnosis, prostate volume, PSA-D, D'Amico risk classification, Gleason grade group, and pathological staging following surgery. RESULTS: The study cohort included 364 patients who underwent Robotic Radical prostatectomy for biopsy-proven clinically localized PCa. 221 (61%) and 143 (39%) patients had PSA-D less than 0.15 and PSA-D more than 0.15, respectively. ISUP GG 1-2 PCa (CS-PCa) was observed in 220 patients (60%), while 144 (40%) had ISUP GG 3-5 PCa at final pathology. PSA-D correlated with CS-PCa only in small and medium-size prostates, but not in large glands (p = .03, p = .01, and p = .36, respectively). The highest sensitivity (72.7%) was observed in small prostates, compared to 3.2% in large prostates. The highest specificity (89.4%) was noted in large prostates. Positive predictive value in small and medium-size prostates was similar (~50%), compared to 20% in large glands. The negative predictive value was slightly better for small and medium-size prostates compared with large glands (68.9%, 73.7%, and 53.1%, respectively). An association between PSA-D and harboring CS-PCa was detected only in small and medium-size glands (72.7% and 43%, respectively). CONCLUSION: PSA-D is associated with CS-PCa detection in radical prostatectomy specimens in small and medium-size prostates. The level of PSA-D is directly associated with the ISUP PCa grade group. Therefore, PSA-D is a beneficial, available, and cost-effective tool during decision-making in patients with small and medium-size prostate when considering treatment for PCa.

Nomogram for predicting disease recurrence after radical cystectomy for transitional cell carcinoma of the bladder.

PURPOSE: American Joint Committee on Cancer staging represents the gold standard for prediction of recurrence after radical cystectomy in patients with invasive bladder cancer. We tested the hypothesis that American Joint Committee on Cancer stage based predictions may be improved when pathological tumor and node stage information is combined with additional clinical and pathological variables within a prognostic nomogram. MATERIALS AND METHODS: We used Cox proportional hazards regression analysis to model variables of 728 patients with transitional cell carcinoma of the bladder treated with radical cystectomy and bilateral pelvic lymphadenectomy at 1 of 3 participating institutions. Standard predictors, pT and pN, were complemented by age, gender, tumor grade at cystectomy, presence of lymphovascular invasion, presence of carcinoma in situ in the cystectomy specimen, neoadjuvant chemotherapy, adjuvant chemotherapy and adjuvant radiotherapy. The concordance index was used to quantify the accuracy of regression coefficient based nomograms. A total of 200 bootstrap resamples were used to reduce overfit bias and for internal validation. Calibration plots were used to graphically explore the performance characteristics of the multivariate nomogram. RESULTS: Followup ranged from 0.1 to 183.4 months (median 24.9, mean 36.4). Recurrence was recorded in 249 (34.2%) patients with a median time to recurrence of 108 months (range 0.8 to 131.9). Actuarial recurrence-free probabilities were 69.6% (95% CI 65.8%-73.0%), 60.2% (55.8%-64.3%) and 52.9% (47.3%-58.1%) at 2, 5 and 8 years after cystectomy, respectively. Two-hundred bootstrap corrected predictive accuracy of American Joint Committee on Cancer stage based predictions was 0.748. Accuracy increased by 3.2% (0.780) when age, lymphovascular invasion, carcinoma in situ, neoadjuvant chemotherapy, adjuvant chemotherapy and adjuvant radiotherapy were added to pathological stage information and used within a nomogram. CONCLUSIONS: A nomogram predicting bladder cancer recurrence after cystectomy is 3.2% more accurate than American Joint Committee on Cancer stage based predictions. Moreover, a nomogram approach combines several advantages such as easy and precise estimation of individual recurrence probability at key points after cystectomy, which all patients deserve to know and all treating physicians need to know.

Clinical outcomes following radical cystectomy for primary nontransitional cell carcinoma of the bladder compared to transitional cell carcinoma of the bladder.

PURPOSE: The effect of bladder cancer histological subtypes other than transitional cell carcinoma (nonTCC) on clinical outcomes remains uncertain. We conducted a multi-institutional retrospective study of patients with bladder cancer treated with radical cystectomy to assess the impact of nonTCC histology on bladder cancer specific outcomes. MATERIALS AND METHODS: A total of 955 consecutive patients underwent radical cystectomy with bilateral pelvic lymphadenectomy for bladder cancer at 3 academic institutions. TCC was present in the radical cystectomy specimen in 888 patients (93%). NonTCC histology was present in 67 patients (7%), including squamous cell carcinoma in 26, adenocarcinoma in 13, small cell carcinoma in 10 and other nonTCC subtypes (ie spindle cell carcinoma, carcinosarcoma and undifferentiated carcinoma) in 18. For patients alive at last followup median followup was 39 and 23 months for patients with TCC and nonTCC histologies, respectively. Bladder cancer specific progression and survival were assessed using Kaplan-Meier and multivariate Cox proportional hazards analyses. RESULTS: Bladder cancer specific progression and mortality did not differ significantly between patients with SCC and TCC histologies. Patients with nonTCC and nonSCC bladder cancer were at significantly increased risk for progression and death compared to patients with TCC or SCC (p <0.001). This association remained statistically significant in patients with organ confined disease (stage pT2 or lower) and patients with nonorgan confined disease (stage pT3 or higher) (p <0.001). In a multivariate analysis nonTCC and nonSCC histology was associated with an increased risk of bladder cancer progression and death (OR 2.272 and 2.585, respectively, p <0.001), even after adjusting for final pathological stage, lymph node status, lymphovascular invasion and neoadjuvant or adjuvant treatments. CONCLUSIONS: NonTCC and nonSCC histological subtype is an independent predictor of bladder cancer progression and mortality in patients undergoing radical cystectomy for bladder cancer. Patients with bladder TCC and SCC share similar stage specific clinical outcomes.