A decision aid versus shared decision making for prostate cancer screening: results of a randomized, controlled trial.

INTRODUCTION: Shared decision making (SDM) is widely encouraged by both the American Urological Association and Choosing Wisely for prostate cancer screening. Implementation of SDM is challenging secondary to time constraints and competing patient priorities. One strategy to mitigate the difficulties in implementing SDM is to utilize a decision aid (DA). Here we evaluate whether a DA improves a patient's prostate cancer knowledge and affects prostate-specific antigen (PSA) screening rates. MATERIALS AND METHODS: Patients were randomized to usual care (UC), DA, or DA + SDM. Perception of quality of care was measured using the Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey. Outcomes were stratified by long term provider relationship (LTPR, > 3 years) versus short term provider relationship (STPR, < 3 years). Knowledge of prostate cancer screening and the decision regarding screening were assessed. Groups were compared using ANOVA and logistic regression models. RESULTS: A total of 329 patients were randomized. Patients in the DA + SDM arm were significantly more likely to report discussing the implication of screening (33% DA + SDM, 22% UC, 16% DA, p = 0.0292) and answered significantly more knowledge questions correctly compared to the UC arm (5.03 versus 4.46, p = 0.046). However, those in the DA arm were significantly less likely to report that they always felt encouraged to discuss all health concerns (72% DA, 78% DA + SDM, 87% UC, p = 0.0285). Interestingly, STPR patients in the DA arm were significantly more likely to undergo PSA-based prostate cancer screening (41%) than the UC arm (8%, p = 0.019). This effect was not observed in the LTPR group. CONCLUSIONS: Providing patients a DA without a personal interaction resulted in a greater chance of undergoing PSA-based screening without improving knowledge about screening or understanding of the consequences of this decision. This effect was exacerbated by a shorter term provider relationship. With complex issues such as the decision to pursue PSA-based prostate cancer screening, tools cannot substitute for direct interaction with a trusted provider.

Functional reprogramming of human prostate cancer to promote local attraction of effector CD8(+) T cells.

BACKGROUND: Local infiltration of CD8(+) T cells (CTLs) in tumor lesions predicts overall clinical outcomes and the clinical benefit of cancer patients from immune checkpoint blockade. In the current study, we evaluated local production of different classes of chemokines in prostate cancer lesions, and the feasibility of their modulation to promote selective entry of CTLs into prostate tumors. METHODS: Chemokine expression in prostate cancer lesion was analyzed by TaqMan-based quantitative PCR, confocal fluorescence microscopy and ELISA. For ex vivo chemokine modulation analysis, prostate tumor explants from patients undergoing primary prostate cancer resections were cultured for 24 hr, in the absence or presence of the combination of poly-I:C, IFNα, and celecoxib (PAC). The numbers of cells producing defined chemokines in the tissues were analyzed by confocal microscopy. Chemotaxis of effector CD8(+) T cells towards the untreated and PAC-treated tumor explant supernatants were evaluated in a standard in vitro migration assays, using 24 well trans-well plates. The number of effector cells that migrated was enumerated by flow cytometry. Pearson (r) correlation was used for analyzing correlations between chemokines and immune filtrate, while paired two tailed students t-test was used for comparison between treatment groups. RESULTS: Prostate tumors showed uniformly low levels of CTL/NK/Th1-recruiting chemokines (CCL5, CXCL9, CXCL10) but expressed high levels of chemokines implicated in the attraction of myeloid derived suppressor cells (MDSC) and regulatory T cells (Treg ): CCL2, CCL22, and CXCL12. Strong positive correlations were observed between CXCL9 and CXCL10 and local CD8 expression. Tumor expression levels of CCL2, CCL22, and CXCL12 were correlated with intratumoral expression of MDSC/Treg markers: FOXP3, CD33, and NCF2. Treatment with PAC suppressed intratumoral production of the Treg -attractant CCL22 and Treg /MDSC-attractant, CXCL12, while increasing the production of the CTL attractant, CXCL10. These changes in local chemokine production were accompanied by the reduced ability of the ex vivo-treated tumors to attract CD4(+) FOXP3(+) Treg cells, and strongly enhanced attraction of the CD8(+) Granzyme B(+) CTLs. CONCLUSIONS: Our data demonstrate that the chemokine environment in prostate cancer can be reprogrammed to selectively enhance the attraction of type-1 effector immune cells and reduce local attraction of MDSCs and Tregs . Prostate 76:1095-1105, 2016. © 2016 Wiley Periodicals, Inc.

Phase II trial of neoadjuvant docetaxel and CG1940/CG8711 followed by radical prostatectomy in patients with high-risk clinically localized prostate cancer.

BACKGROUND: Prostate cancer (PC) is the most commonly diagnosed noncutaneous malignancy in American men. PC, which exhibits a slow growth rate and multiple potential target epitopes, is an ideal candidate for immunotherapy. GVAX for prostate cancer is a cellular immunotherapy, composed of PC-3 cells (CG1940) and LNCaP cells (CG8711). Each of the components is a prostate adenocarcinoma cell line that has been genetically modified to secrete granulocyte-macrophage colony-stimulating factor. Hypothesizing that GVAX for prostate cancer could be effective in a neoadjuvant setting in patients with locally advanced disease, we initiated a phase II trial of neoadjuvant docetaxel and GVAX. For the trial, the clinical effects of GVAX were assessed in patients undergoing radical prostatectomy (RP). METHODS: Patients received docetaxel administered at a dose of 75 mg/m(2) every 3 weeks for 4 cycles. GVAX was administered 2-3 days after chemotherapy preoperatively for four courses of immunotherapy. The first dose of GVAX was a prime immunotherapy of 5×10(8) cells. The subsequent boost immunotherapies consisted of 3×10(8) cells. After RP, patients received an additional six courses of immunotherapy. Pathologic complete response, toxicity, and clinical response were assessed. The primary endpoint of the trial was a pathologic state of pT0, which is defined as no evidence of cancer in the prostate. RESULTS: Six patients completed neoadjuvant docetaxel and GVAX therapy. No serious drug-related adverse events were observed. Median change in prostate-specific antigen (PSA) following neoadjuvant therapy was 1.47 ng/ml. One patient did not undergo RP due to the discovery of positive lymph nodes during exploration. Of the five patients completing RP, four had a downstaging of their Gleason score. Undetectable PSA was achieved in three patients at 2 months after RP and in two patients at 3 years after RP. CONCLUSIONS: Neoadjuvant docetaxel/GVAX is safe and well tolerated in patients with high-risk locally advanced PC. No evidence of increased intraoperative hemorrhage or increased length of hospital stay postoperatively was noted. These results justify further study of neoadjuvant immunotherapy.

Increasing Adherence to an AUA Guideline: A Durable Impact on Immediate Postoperative Mitomycin C Use.

INTRODUCTION: In this quality initiative we assessed whether providing surgeons with the American Urological Association guideline regarding intravesical mitomycin C at the time of surgery scheduling impacts compliance. Furthermore, we examined the durability of the intervention and the influence of surgeon volume on guideline adherence. METHODS: All patients (105) undergoing transurethral bladder tumor resection from July 2015 to February 2016 at Virginia Mason Medical Center were included prospectively. At the scheduling of surgery urologists were provided with a preoperative tool that included the relevant guideline. Mitomycin C use during the study period was compared to historical and subsequent year's use. Additionally, we stratified results by high and low volume resectionists. RESULTS: Before this study mitomycin C was used in 17.1% (25 of 146) of all resections. During the intervention period its use nearly tripled to 43% (28 of 65), an increase of 25.9%. The year after the intervention its use decreased to 32.7% (36 of 110). Durability was strongest for high volume surgeons and trended toward significance for low volume surgeons. CONCLUSIONS: Providing surgeons with a copy of the guideline at the time of surgery scheduling resulted in a threefold increase in guideline compliance. This change is durable and most impactful for higher volume surgeons. We believe this model can be used to ensure adherence and consideration for many guidelines.

Cytologic persistence of malignant cells after transurethral resection of bladder tumors: Implications for concomitant manipulation of the urinary tract at the time of endoscopic resection.

BACKGROUND: The current study was conducted to determine the feasibility of cytologically clearing the bladder of tumor cells after transurethral resection of bladder tumor (TURBT) and aggressive serial bladder washing. METHODS: A prospective pilot sample of 20 patients with known bladder masses was enrolled before undergoing TURBT. Preoperative cytology and 4 postoperative cytology specimens were assessed for malignant cells between serial bladder washes. Surgeons assessed tumor grade visually at the time of TURBT. RESULTS: Surgeons were able to differentiate high-grade disease with limited accuracy (75% sensitivity, 92% specificity, 85% negative predictive value, and 86% positive predictive value). For patients with low-grade disease (12 patients), cytology was atypical in 25% of patients immediately before TURBT and was negative after serial washings in all patients. In patients with high-grade disease (8 patients), approximately 75% had cytology consistent with high-grade urothelial carcinoma immediately before TURBT and only 1 patient was cleared cytologically after serial bladder washings. CONCLUSIONS: In patients with high-grade disease, serial bladder washing after TURBT does not appear to clear malignant cells as detected by cytology. This theoretical oncologic risk should be weighed when considering concomitant upper tract procedures such as retrograde pyelography. Future work is needed to quantify risk. Cancer Cytopathol 2017;125:114-119. © 2016 American Cancer Society.