Qualitative research aimed at identifying patient acceptance of active surveillance (AS) has been identified as a public health research priority. The primary objective of this study was to determine ...if analysis of a large-sample of anonymous internet conversations (ICs) could be utilized to identify unmet public needs regarding AS.
English-language ICs regarding prostate cancer (PC) treatment with AS from 2002-12 were identified using a novel internet search methodology. Web spiders were developed to mine, aggregate, and analyze content from the world-wide-web for ICs centered on AS. Collection of ICs was not restricted to any specific geographic region of origin. NLP was used to evaluate content and perform a sentiment analysis. Conversations were scored as positive, negative, or neutral. A sentiment index (SI) was subsequently calculated according to the following formula to compare temporal trends in public sentiment towards AS: (# Positive IC/#Total IC)-(#Negative IC/#Total IC) x 100.
A total of 464 ICs were identified. Sentiment increased from -13 to +2 over the study period. The increase sentiment has been driven by increased patient emphasis on quality-of-life factors and endorsement of AS by national medical organizations. Unmet needs identified in these ICs include: a gap between quantitative data regarding long-term outcomes with AS vs. conventional treatments, desire for treatment information from an unbiased specialist, and absence of public role models managed with AS.
This study demonstrates the potential utility of online patient communications to provide insight into patient preferences and decision-making. Based on our findings, we recommend that multidisciplinary clinics consider including an unbiased specialist to present treatment options and that future decision tools for AS include quantitative data regarding outcomes after AS.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Renal cell carcinoma (RCC) is a common diagnosis, of which a notable portion of patients present with an extension into the venous circulation causing an inferior vena cava (IVC) tumor thrombus. ...Venous extension has significant implications for staging and subsequent treatment planning, with recommendations for more aggressive surgical removal, although associated surgical morbidity and mortality is relatively increased. The methods for surgical removal of RCC with IVC thrombus remain complex, particularly surrounding the use of robot-assisted surgery. Robot assistance for radical nephrectomy in this context is recently emerging. Thrombus level has important implications for surgical technique and prognosis. Other preoperative considerations may include location, laterality, size, and wall invasion. The urology literature on treatment of such tumors is largely limited to case series and institutional studies that describe the feasibility of various surgical options for these complex tumors. Further understanding of the outcomes and patient-specific risk factors would shed increased light on the optimal treatment for such cases. This narrative review provides a thorough overview on the previously reported use of robot-assisted nephrectomy in RCC with IVC thrombus to inform further studies which may optimize outcomes and guide shared decision-making.
Autologous dendritic cells (DCs) transfected with mRNA encoding prostate-specific antigen (PSA) are able to stimulate potent, T cell-mediated antitumor immune responses in vitro. A phase I trial was ...performed to evaluate this strategy for safety, feasibility, and efficacy to induce T cell responses against the self-protein PSA in patients with metastatic prostate cancer. In 13 study subjects, escalating doses of PSA mRNA-transfected DCs were administered with no evidence of dose-limiting toxicity or adverse effects, including autoimmunity. Induction of PSA-specific T cell responses was consistently detected in all patients, suggesting in vivo bioactivity of the vaccine. Vaccination was further associated with a significant decrease in the log slope PSA in six of seven subjects; three patients that could be analyzed exhibited a transient molecular clearance of circulating tumor cells. The demonstration of vaccine safety, successful in vivo induction of PSA-specific immunity, and impact on surrogate clinical endpoints provides a scientific rationale for further clinical investigation of RNA-transfected DCs in the treatment of human cancer.
DNA-dependent protein kinase catalytic subunit (DNA-PK) is a pleiotropic kinase involved in DNA repair and transcriptional regulation. DNA-PK is deregulated in selected cancer types and is strongly ...associated with poor outcome. The underlying mechanisms by which DNA-PK promotes aggressive tumor phenotypes are not well understood. Here, unbiased molecular investigation in clinically relevant tumor models reveals novel functions of DNA-PK in cancer.
DNA-PK function was modulated using both genetic and pharmacologic methods in a series of
models,
xenografts, and patient-derived explants (PDE), and the impact on the downstream signaling and cellular cancer phenotypes was discerned. Data obtained were used to develop novel strategies for combinatorial targeting of DNA-PK and hormone signaling pathways.
Key findings reveal that (i) DNA-PK regulates tumor cell proliferation; (ii) pharmacologic targeting of DNA-PK suppresses tumor growth both
, and
; (iii) DNA-PK transcriptionally regulates the known DNA-PK-mediated functions as well as novel cancer-related pathways that promote tumor growth; (iv) dual targeting of DNA-PK/TOR kinase (TORK) transcriptionally upregulates androgen signaling, which can be mitigated using the androgen receptor (AR) antagonist enzalutamide; (v) cotargeting AR and DNA-PK/TORK leads to the expansion of antitumor effects, uncovering the modulation of novel, highly relevant protumorigenic cancer pathways; and (viii) cotargeting DNA-PK/TORK and AR has cooperative growth inhibitory effects
and
.
These findings uncovered novel DNA-PK transcriptional regulatory functions and led to the development of a combinatorial therapeutic strategy for patients with advanced prostate cancer, currently being tested in the clinical setting.
Prostate cancer (PCA) germline testing (GT) is now standard-of-care for men with advanced PCA. Thousands of men may consider GT due to clinical and family history (FH) features. Identifying and ...consenting men for GT can be complex. Here we identified barriers and facilitators of GT across a spectrum of providers which informed the development of Helix – an educational and clinical/FH collection tool to facilitate GT in practice.
A 12-question survey assessing knowledge of genetics PCA risk and FH was administered December 2017 to March 2018 in the Philadelphia area and at the Mid-Atlantic AUA meeting (March 2018). Responses were analyzed using descriptive statistics. Semi-structured interviews were conducted with medical oncologists, radiation oncologists, and urologists across practice settings from March-October 2020 as part of a larger study based on the Tailored Implementation in Chronic Diseases framework. Helix was then developed followed by user testing.
Fifty-six providers (50% urologists) responded to the survey. Multiple FH and genetic knowledge gaps were identified: only 66% collected maternal FH and 43% correctly identified BRCA2 and association to aggressive PCA. Genetic counseling gaps included low rates of discussing genetic discrimination laws (45%). Provider interviews (n = 14) identified barriers to FH intake including access to details and time needed. In user testing (n = 10), providers found Helix helpful for FH collection. All providers found Helix easy to use, suggesting expanded clinical use.
Helix addressed multiple GT knowledge and practice gaps across a spectrum of providers. This tool will become publicly available soon to facilitate PCA GT in clinical practice.
Prostate cancer germline testing informs precision therapy, screening, and hereditary cancer risk. Identifying and consenting for germline testing is complex, requiring new practice strategies. We identified multiple knowledge and practice gaps among a spectrum of providers which informed the development of Helix, a digital educational and clinical/family history collection tool. User testing was promising, supporting clinical use of Helix.
To investigate the long-term impact of contrast-enhanced ultrasound (CEUS) on the treatment of patients with indeterminate renal masses.
In this retrospective study, consecutive charts of all ...patients receiving renal CEUS at 1 of 2 academic medical centers between January 1, 2014, and December 31, 2018, were reviewed. Patients were included in the study if they had documented chronic renal disease (estimated glomerular filtration rate < 60 mL/min/1.73 m
) or prior nephrectomy and received CEUS for a previously untreated renal mass.
A total of 215 lesions in 157 patients were used for analysis. Contrast-enhanced ultrasound provided a final treatment recommendation in 71.6% of lesions (154 of 215). Of these 154 lesions, 7.8% (12 of 154) were lost to follow-up despite CEUS suggesting malignancy; 15.6% (24 of 154) went directly for surgical intervention, with malignancy confirmed by pathologic results in 87.5% (21 of 24) of these cases; and the remaining 76.6% (118 of 154) were deemed benign and required no additional follow-up. Of the 118 lesions diagnosed by CEUS as benign and requiring no follow-up, none showed evidence of later renal cell carcinoma development and, only 5.1% (6 of 118) of the total population was referred for further cross-sectional imaging of the mass in question. In 28.4% of all lesions (61 of 215), CEUS resulted in a recommendation for surveillance imaging at a 6- to 12-month interval, and less than 10% (6 of 61) of these underwent additional cross-sectional imaging within the recommended 6 months after CEUS.
These findings highlight the impact of CEUS on clinical treatment of indeterminate renal masses, including reducing the use of the potentially nephrotoxic contrast agents and providing a direct pathway to transplant.
New-generation flexible ureteroscopes allow the management of proximal ureteral and intrarenal pathology with high success rates, including complete removal of ureteral and renal calculi. One problem ...is that the irrigation pressures generated within the collecting system can be significantly elevated, as evidenced by pyelovenous and pyelolymphatic backflow seen during retrograde pyelography. We sought to determine if the ureteral access sheath (UAS) can offer protection from high intrarenal pressures attained during routine ureteroscopic stone surgery.
Five patients (average age 72.6 years) evaluated in the emergency department for obstructing calculi underwent percutaneous nephrostomy (PCN) tube placement to decompress their collecting systems. The indications for PCN tube placement were obstructive renal failure (N=1), urosepsis (N=2), and obstruction with uncontrolled pain and elevated white blood cell counts (N=2). Flexible ureteroscopy was subsequently performed with and without the aid of the UAS while pressures were measured via the nephrostomy tube connected to a pressure transducer. Pressures were recorded at baseline and in the distal, mid, and proximal ureter and renal pelvis, first without the UAS, and then with the UAS in place.
The average baseline pressure within the collecting system was 13.6 mm Hg. The mean intrarenal pressure with the ureteroscope in the distal ureter without the UAS was 60 mm Hg and with the UAS was 15 mm Hg. With the ureteroscope in the midureter, the pressures were 65.6 and 17.5 mm Hg, respectively; with the ureteroscope in the proximal ureter 79.2 and 24 mm Hg, and with the ureteroscope in the renal pelvis 94.4 and 40.6 mm Hg, respectively. All differences at each location were statistically significant (P<0.008). Compared with baseline, all pressures measured without the UAS were significantly greater, but only pressures recorded in the proximal ureter and renal pelvis after UAS insertion were significantly higher (P<0.03).
The irrigation pressures transmitted to the renal pelvis and subsequently to the parenchyma are significantly greater during routine URS without the use of the UAS. The access sheath is potentially protective against pyelovenous and pyelolymphatic backflow, with clinical implications for the ureteroscopic management of upper-tract transitional cell carcinoma, struvite stones, or calculi associated with urinary tract infection.
Objectives
Vascular assessment of indeterminate renal masses (iRMs) remains a crucial element of diagnostic imaging, as the presence of blood flow within renal lesions suggests malignancy. We ...compared the utility of Superb Microvascular Imaging (SMI; Canon Medical Systems, Tustin, CA), a novel Doppler technique, to standard color Doppler imaging (CDI) and power Doppler imaging (PDI) for the detection of vascularity within iRMs.
Methods
Patients undergoing contrast‐enhanced ultrasound (CEUS) evaluations for iRMs first underwent a renal ultrasound examination with the following modes: CDI, PDI, color Superb Microvascular Imaging (cSMI), and monochrome Superb Microvascular Imaging (mSMI), using an Aplio i800 scanner with an i8CX1 transducer (Canon Medical Systems). After image randomization, each mode was assessed for iRM vascularity by 4 blinded readers on a diagnostic confidence scale of 1 to 5 (5 = most confident). The results were compared to CEUS as the reference standard.
Results
Forty‐one patients with 50 lesions met inclusion criteria. Relative to the other 3 modalities, mSMI had the highest sensitivity (63.3%), whereas cSMI had the highest specificity (62.1%). Both cSMI and mSMI also had the highest diagnostic accuracy (0.678 and 0.680, respectively; both P < 0.001) compared to CDI (0.568) and PDI (0.555). Although the reader‐reported confidence interval of mSMI (mean ± SD, 3.6 ± 1.1) was significantly lower than CDI (4.1 ± 1.0) and PDI (4.0 ± 1.0; P < 0.001), the confidence level of cSMI (4.1 ± 0.9) was not (P > 0.173).
Conclusions
Preliminary data suggest that SMI is a potentially useful modality in detecting microvasculature in iRMs compared to standard Doppler techniques. Future studies should aim to compare the efficacy of both SMI and CEUS and to assess the ability of SMI to characterize malignancy in iRMs.
Despite results of randomized trials that support adjuvant radiation therapy (RT) after radical prostatectomy (RP) for prostate cancer with adverse pathologic features (APF), many clinicians favor ...selective use of salvage RT. This survey was conducted to evaluate the beliefs and practices of radiation oncologists (RO) and urologists (U) regarding RT after RP.
We designed a Web-based survey of post-RP RT beliefs and policies. Survey invitations were e-mailed to a list of 926 RO and 591 U. APF were defined as extracapsular extension, seminal vesicle invasion, or positive surgical margin. Differences between U and RO in adjuvant RT recommendations were evaluated by comparative statistics. Multivariate analyses were performed to evaluate factors predictive of adjuvant RT recommendation.
Analyzable surveys were completed by 218 RO and 92 U (overallresponse rate, 20%). Adjuvant RT was recommended based on APF by 68% of respondents (78% RO, 44% U, p <0.001). U were less likely than RO to agree that adjuvant RT improves survival and/or biochemical control (p < 0.0001). PSA thresholds for salvage RT were higher among U than RO (p < 0.001). Predicted rates of erectile dysfunction due to RT were higher among U than RO (p <0.001). On multivariate analysis, respondent specialty was the only predictor of adjuvant RT recommendations.
U are less likely than RO to recommend adjuvant RT. Future research efforts should focus on defining the toxicities of post-RP RT and on identifying the subgroups of patients who will benefit from adjuvant vs. selective salvage RT.
Cabazitaxel has been demonstrated to improve the overall survival for men with metastatic castrate-resistant prostate cancer. The purpose of this study was to determine the maximum tolerated dose for ...concurrent cabazitaxel with androgen deprivation and intensity modulated radiation therapy in men with high-risk prostate cancer.
Twenty men were enrolled in this institutuional review board-approved phase I clinical trial using a 3 + 3 design. Patients were followed prospectively for safety, efficacy, and health-related quality of life (Expanded Prostate Index Composite). Efficacy was assessed biochemically using the Phoenix definition.
With a median follow-up time of 56 months, the maximum tolerated dose of concurrent cabazitaxel was 6 mg/m
. The 5-year biochemical disease-free survival was 73%, despite 75% of patients having very high risk prostate cancer per the National Comprehensive Cancer Network guidelines. Four patients were unable to complete chemotherapy owing to dose-limiting toxicities (eg, rectal bleeding, diarrhea, and elevated transaminase). There was no significant minimally important difference in Expanded Prostate Index Composite patient-reported outcomes for either the urinary or bowel domains; however, there was a significant decrease in the sexual domain.
This is the first clinical trial of prostate cancer to report on the combination of cabazitaxel and radiation therapy. The maximum tolerated dose of concurrent cabazitaxel with radiation and androgen deprivation therapy was determined to be 6 mg/m
. Despite the aggressive nature of the disease, robust biochemical control was observed.
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