Concomitant CIS on TURBT does not impact oncological outcomes in patients treated with neoadjuvant or induction chemotherapy followed by radical cystectomy.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer improves all-cause and cancer specific survival. We aimed to evaluate whether the detection of carcinoma in situ (CIS) at the time of initial transurethral resection of bladder tumor (TURBT) has an oncological impact on the response to NAC prior to radical cystectomy. PATIENTS AND METHODS: Patients were identified retrospectively from 19 centers who received at least three cycles of NAC or induction chemotherapy for cT2-T4aN0-3M0 urothelial carcinoma of the bladder followed by radical cystectomy between 2000 and 2013. The primary and secondary outcomes were pathological response and overall survival, respectively. Multivariable analysis was performed to determine the independent predictive value of CIS on these outcomes. RESULTS: Of 1213 patients included in the analysis, 21.8% had concomitant CIS. Baseline clinical and pathologic characteristics of the 'CIS' versus 'no-CIS' groups were similar. The pathological response did not differ between the two arms when response was defined as pT0N0 (17.9% with CIS vs 21.9% without CIS; p = 0.16) which may indicate that patients with CIS may be less sensitive to NAC or ≤ pT1N0 (42.8% with CIS vs 37.8% without CIS; p = 0.15). On Cox regression model for overall survival for the cN0 cohort, the presence of CIS was not associated with survival (HR 0.86 (95% CI 0.63-1.18; p = 0.35). The presence of LVI (HR 1.41, 95% CI 1.01-1.96; p = 0.04), hydronephrosis (HR 1.63, 95% CI 1.23-2.16; p = 0.001) and use of chemotherapy other than ddMVAC (HR 0.57, 95% CI 0.34-0.94; p = 0.03) were associated with shorter overall survival. For the whole cohort, the presence of CIS was also not associated with survival (HR 1.05 (95% CI 0.82-1.35; p = 0.70). CONCLUSION: In this multicenter, real-world cohort, CIS status at TURBT did not affect pathologic response to neoadjuvant or induction chemotherapy. This study is limited by its retrospective nature as well as variability in chemotherapy regimens and surveillance regimens.

Frequent PD-L1 expression in primary and metastatic penile squamous cell carcinoma: potential opportunities for immunotherapeutic approaches.

BACKGROUND: Despite aggressive multimodal therapy, locally advanced and/or metastatic penile squamous cell carcinoma (SqCC) is associated with significant morbidity and mortality, indicating a need for new therapeutic options. Given the emerging clinical utility of immunotherapeutics, we sought to assess the incidence and potential clinical significance of PD-L1 expression in penile SqCC. PATIENTS AND METHODS: Using an anti-PD-L1 primary antibody (clone 5H1), immunohistochemistry was carried out on whole tumor sections from 37 patients with penile SqCC treated at our institution between 2005 and 2013. PD-L1-positive tumors were defined as those with membranous staining in ≥5% of tumor cells. Association between PD-L1 expression and clinicopathologic parameters was examined using Fisher's exact test. Correlation between PD-L1 expression in primary tumors and matched metastases was assessed using the Spearman rank correlation coefficient (ρ). The difference in cancer-specific mortality between PD-L1-positive and -negative groups was examined using the log-rank test. RESULTS: Twenty-three (62.2%) of 37 primary tumors were positive for PD-L1 expression, and there was strong positive correlation of PD-L1 expression in primary and metastatic samples (ρ = 0.72; 0.032 < P < 0.036). Primary tumor PD-L1 expression was significantly associated with usual type histology (P = 0.040) and regional lymph node metastasis (P = 0.024), as well as decreased cancer-specific survival (P = 0.011). CONCLUSIONS: The majority of primary penile SqCC tumors express PD-L1, which is associated with high-risk clinicopathologic features and poor clinical outcome. These data provide a rational basis for further investigation of anti-PD-1 and anti-PD-L1 immunotherapeutics in patients with advanced penile SqCC.

Mass-like peripheral zone enhancement on CT is predictive of higher-grade (Gleason 4 + 3 and higher) prostate cancer.

PURPOSE: To determine whether focal peripheral zone enhancement on routine venous-phase CT is predictive of higher-grade (Gleason 4 + 3 and higher) prostate cancer. MATERIALS AND METHODS: IRB approval was obtained and informed consent waived for this HIPAA-compliant retrospective study. Forty-three patients with higher-grade prostate cancer (≥Gleason 4 + 3) and 96 with histology-confirmed lower-grade (≤Gleason 3 + 4 [n = 47]) or absent (n = 49) prostate cancer imaged with venous-phase CT comprised the study population. CT images were reviewed by ten blinded radiologists (5 attendings, 5 residents) who scored peripheral zone enhancement on a scale of 1 (benign) to 5 (malignant). Mass-like peripheral zone enhancement was considered malignant. Likelihood ratios (LR) and specificities were calculated. Multivariate conditional logistic regression analyses were conducted. RESULTS: Scores of "5" were strongly predictive of higher-grade prostate cancer (pooled LR+ 9.6 [95% CI 5.8-15.8]) with rare false positives (pooled specificity: 0.98 [942/960, 95% CI 0.98-0.99]; all 10 readers had specificity ≥95%). Attending scores of "5" were more predictive than resident scores of "5" (LR+: 14.7 [95% CI 5.8-37.2] vs. 7.6 [95% CI 4.2-13.7]) with similar specificity (0.99 [475/480, 95% CI 0.98-1.00] vs. 0.97 [467/480, 95% CI 0.96-0.99]). Significant predictors of an assigned score of "5" included presence of a peripheral zone mass (p < 0.0001), larger size (p < 0.0001), and less reader experience (p = 0.0008). Significant predictors of higher-grade prostate cancer included presence of a peripheral zone mass (p = 0.0002) and larger size (p < 0.0001). CONCLUSION: Focal mass-like peripheral zone enhancement on routine venous-phase CT is specific and predictive of higher-grade (Gleason 4 + 3 and higher) prostate cancer.

Nomogram Predicting Bladder Cancer-specific Mortality After Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-invasive Bladder Cancer: Results of an International Consortium.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) is associated with improved overall and cancer-specific survival. The post-NAC pathological stage has previously been reported to be a major determinant of outcome. OBJECTIVE: To develop a postoperative nomogram for survival based on pathological and clinical parameters from an international consortium. DESIGN, SETTING, AND PARTICIPANTS: Between 2000 and 2015, 1866 patients with MIBC were treated at 19 institutions in the USA, Canada, and Europe. Analysis was limited to 640 patients with adequate follow-up who had received three or more cycles of NAC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A nomogram for bladder cancer-specific mortality (BCSM) was developed by multivariable Cox regression analysis. Decision curve analysis was used to assess the model's clinical utility. RESULTS AND LIMITATIONS: A total of 640 patients were identified. Downstaging to non-MIBC (ypT1, ypTa, and ypTis) occurred in 271 patients (42 %), and 113 (17 %) achieved a complete response (ypT0N0). The 5-yr BCSM was 47.2 % (95 % confidence interval [CI]: 41.2-52.6 %). On multivariable analysis, covariates with a statistically significant association with BCSM were lymph node metastasis (hazard ratio [HR] 1.90 [95% CI: 1.4-2.6]; p < 0.001), positive surgical margins (HR 2.01 [95 % CI: 1.3-2.9]; p < 0.001), and pathological stage (with ypT0/Tis/Ta/T1 as reference: ypT2 [HR 2.77 {95 % CI: 1.7-4.6}; p < 0.001] and ypT3-4 [HR 5.9 {95 % CI: 3.8-9.3}; p < 0.001]). The area under the curve of the model predicting 5-yr BCSM after cross validation with 300 bootstraps was 75.4 % (95 % CI: 68.1-82.6 %). Decision curve analyses showed a modest net benefit for the use of the BCSM nomogram in the current cohort compared with the use of American Joint Committee on Cancer staging alone. Limitations include the retrospective study design and the lack of central pathology. CONCLUSIONS: We have developed and internally validated a nomogram predicting BCSM after NAC and radical cystectomy for MIBC. The nomogram will be useful for patient counseling and in the identification of patients at high risk for BCSM suitable for enrollment in clinical trials of adjuvant therapy. PATIENT SUMMARY: In this report, we looked at the outcomes of patients with muscle-invasive bladder cancer in a large multi-institutional population. We found that we can accurately predict death after radical surgical treatment in patients treated with chemotherapy before surgery. We conclude that the pathological report provides key factors for determining survival probability.

Teenage pregnancy: family syndrome?

A short term, longitudinal study was conducted in order to explore selected psychosocial characteristics of fourteen teenagers aged sixteen years or younger who became mothers, the subsequent interaction of the mother-infant dyads, and the development and attachment of their infants at twelve months. The sample was matched for socioeconomic and marital status, intellectual ability and ethnicity with non-pregnant teenagers and pregnant women twenty years or older. The subjects were given a psychological and social history test battery. The groups did not differ significantly on the personality tests. The pregnant women reported a significantly poorer daughter-father relationship than the nonpregnant controls. In a high proportion of cases it was found that their fathers were absent or ineffectual and the homes mother-ridden. The interview data suggest that a large number of the pregnancies were psychologically motivated.

The androgen receptor gene and its influence on the development and progression of prostate cancer.

Prostate adenocarcinoma has the highest incidence of any malignancy and is the second leading cause of cancer-related deaths in men in industrialized countries. The development and progression of prostate cancer are dependent on testosterone and dihydrotestosterone; the androgen receptor is the vehicle through which these androgens exert their regulation on prostate cellular proliferation and differentiation. As a result, much effort has been devoted to elucidating the role of the androgen receptor in prostate cancer. The CAG and GGN trinucleotide repeats in exon 1 of the androgen receptor gene have been linked to prostate cancer risk and progression in some studies. Also, androgen receptor gene amplification may be a mechanism of prostate cancer cell adaptation to hormonal therapy. In addition, androgen receptor somatic mutations can result in receptors that have altered binding specificity when compared with wild-type receptors and heightened affinity for hormones other than testosterone and dihydrotestosterone. Gene amplification and somatic mutations, coupled with the fact that various growth factors have been shown to stimulate androgen receptor activity independently of androgens, may enable prostate cancer cells to grow despite testicular-androgen ablation. Unfortunately, current medical therapy for metastatic prostate cancer is deficient, hormone-refractory prostate cancer is a major obstacle in treatment, and, as a result, prostate cancer mortality is still significant. Further study of the function of the androgen receptor will offer a better understanding of prostate cancer pathogenesis and progression, aiding the development of more effective treatments for this disease.