Publications by authors named "Jason A Efstathiou"

177 Publications

Trimodality Therapy With or Without Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer.

Clin Genitourin Cancer 2021 Mar 16. Epub 2021 Mar 16.

Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, GA.

Background: Bladder-sparing chemoradiation therapy is a definitive first-line treatment option for muscle-invasive bladder cancer. Randomized trials have demonstrated that the addition of neoadjuvant chemotherapy to radical cystectomy or radiation monotherapy results in a survival benefit. Whether neoadjuvant chemotherapy improves outcomes when used with definitive chemoradiation is unknown.

Patients And Methods: We identified 2566 patients in the National Cancer Data Base with cT2-4N0M0 urothelial cell carcinoma of the bladder treated with definitive intent concurrent chemoradiation from 2004 to 2015. The exposure of interest was receipt of neoadjuvant chemotherapy versus those without neoadjuvant chemotherapy. The primary outcome was overall survival defined from the time of diagnosis. Kaplan-Meier and multivariable Cox proportional hazard analyses were used to compare survival between groups. Sensitivity analyses tested (1) an interaction term for clinical T stage and (2) defining survival from start of radiation (as opposed to time of diagnosis) to address potential leading time bias.

Results: We identified 462 patients treated with neoadjuvant chemotherapy followed by chemoradiation and 2104 patients treated with chemoradiation alone. With a median follow-up of 6.2 years, we found no difference in survival between groups: 5-year or 10-year overall survival of 30.6% (95% confidence interval [CI], 28.4%-32.9%) in the neoadjuvant group versus 31.8% (95% CI, 27.0%-36.8%) in the standard chemoradiation therapy group and 13.3% (95% CI, 11.2%-15.5%) in the neoadjuvant group versus 13.0% (95% CI, 8.4%-18.7%) in the standard chemoradiation therapy group, respectively (log-rank P = .19). On multivariable analysis we found no association between receipt of neoadjuvant chemotherapy and overall survival (hazard ratio, 1.01; 95% CI, 0.88-1.15; P = .921). The sensitivity analyses did not identify any differential effect by clinical T stage nor by defining survival from start of radiation.

Conclusion: These results do not support the routine addition of neoadjuvant chemotherapy to definitive chemoradiation for bladder cancer, and optimizing the chemotherapy sequencing and regimens for bladder-preserving approaches to muscle invasive bladder cancer should continue to be studied under prospective clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clgc.2021.03.007DOI Listing
March 2021

Complications and Outcomes of Salvage Cystectomy after Trimodality Therapy.

J Urol 2021 Feb 22:101097JU0000000000001696. Epub 2021 Feb 22.

Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

Purpose: Salvage cystectomy is required for some patients with intravesical recurrence after trimodality therapy. We compared postoperative outcomes between salvage cystectomy post-trimodality therapy, primary cystectomy and primary cystectomy with prior history of nontrimodality therapy abdominal or pelvic radiotherapy.

Materials And Methods: We included 265 patients who underwent radical cystectomy at Massachusetts General Hospital for cT1-T4 bladder cancer between 2003 and 2013. Patients were grouped as salvage cystectomy post-trimodality therapy, primary cystectomy or primary cystectomy with prior history of nontrimodality therapy abdominal or pelvic radiotherapy. Early (≤90 days) and late (>90 days) complications were compared. Disease-specific survival and overall survival were calculated using a Cox regression model, and adjusted survival curves were generated.

Results: The median followup from the time of cystectomy was 65.5 months. There was no difference in intraoperative and early complications between the groups. The detection of late complications was higher in salvage cystectomy post-trimodality therapy compared to primary cystectomy and primary cystectomy with prior history of nontrimodality therapy abdominal or pelvic radiotherapy (p=0.03). In multivariable Cox regression analysis, salvage cystectomy post-trimodality therapy was associated with a higher incidence of any late (HR 2.3, p=0.02) and major late complications (HR 2.1, p <0.05). There was no difference in disease-specific survival (p=0.8) or overall survival (p=0.9) between the groups.

Conclusions: Salvage cystectomy post-trimodality therapy for intravesical recurrence post-trimodality therapy has an intraoperative and early complication rate comparable to primary cystectomy and primary cystectomy with prior history of nontrimodality therapy abdominal or pelvic radiotherapy. Salvage cystectomy post-trimodality therapy is associated with a higher risk of overall and major late complications than primary cystectomy. The disease-specific survival and overall survival of patients who require salvage cystectomy post-trimodality therapy are comparable to both groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JU.0000000000001696DOI Listing
February 2021

Validation of a 22-Gene Genomic Classifier in Patients With Recurrent Prostate Cancer: An Ancillary Study of the NRG/RTOG 9601 Randomized Clinical Trial.

JAMA Oncol 2021 Apr;7(4):544-552

Department of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland.

Importance: Decipher (Decipher Biosciences Inc) is a genomic classifier (GC) developed to estimate the risk of distant metastasis (DM) after radical prostatectomy (RP) in patients with prostate cancer.

Objective: To validate the GC in the context of a randomized phase 3 trial.

Design, Setting, And Participants: This ancillary study used RP specimens from the phase 3 placebo-controlled NRG/RTOG 9601 randomized clinical trial conducted from March 1998 to March 2003. The specimens were centrally reviewed, and RNA was extracted from the highest-grade tumor available in 2019 with a median follow-up of 13 years. Clinical-grade whole transcriptomes from samples passing quality control were assigned GC scores (scale, 0-1). A National Clinical Trials Network-approved prespecified statistical plan included the primary objective of validating the independent prognostic ability of GC for DM, with secondary end points of prostate cancer-specific mortality (PCSM) and overall survival (OS). Data were analyzed from September 2019 to December 2019.

Intervention: Salvage radiotherapy (sRT) with or without 2 years of bicalutamide.

Main Outcomes And Measures: The preplanned primary end point of this study was the independent association of the GC with the development of DM.

Results: In this ancillary study of specimens from a phase 3 randomized clinical trial, GC scores were generated from 486 of 760 randomized patients with a median follow-up of 13 years; samples from a total of 352 men (median [interquartile range] age, 64.5 (60-70) years; 314 White [89.2%] participants) passed microarray quality control and comprised the final cohort for analysis. On multivariable analysis, the GC (continuous variable, per 0.1 unit) was independently associated with DM (hazard ratio [HR], 1.17; 95% CI, 1.05-1.32; P = .006), PCSM (HR, 1.39; 95% CI, 1.20-1.63; P < .001), and OS (HR, 1.17; 95% CI, 1.06-1.29; P = .002) after adjusting for age, race/ethnicity, Gleason score, T stage, margin status, entry prostate-specific antigen, and treatment arm. Although the original planned analysis was not powered to detect a treatment effect interaction by GC score, the estimated absolute effect of bicalutamide on 12-year OS was less when comparing patients with lower vs higher GC scores (2.4% vs 8.9%), which was further demonstrated in men receiving early sRT at a prostate-specific antigen level lower than 0.7 ng/mL (-7.8% vs 4.6%).

Conclusions And Relevance: This ancillary validation study of the Decipher GC in a randomized trial cohort demonstrated association of the GC with DM, PCSM, and OS independent of standard clinicopathologic variables. These results suggest that not all men with biochemically recurrent prostate cancer after surgery benefit equally from the addition of hormone therapy to sRT.

Trial Registration: ClinicalTrials.gov identifier: NCT00002874.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoncol.2020.7671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879385PMC
April 2021

Management of Muscle-Invasive Bladder Cancer During a Pandemic: Impact of Treatment Delay on Survival Outcomes for Patients Treated With Definitive Concurrent Chemoradiotherapy.

Clin Genitourin Cancer 2021 02 22;19(1):41-46.e1. Epub 2020 Jun 22.

Department of Radiation Oncology, Washington University School of Medicine in St Louis, St Louis, MO; Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. Electronic address:

Introduction: During the coronavirus disease 2019 (COVID-19) pandemic, providers and patients must engage in shared decision making to ensure that the benefit of early intervention for muscle-invasive bladder cancer exceeds the risk of contracting COVID-19 in the clinical setting. It is unknown whether treatment delays for patients eligible for curative chemoradiation (CRT) compromise long-term outcomes.

Patients And Methods: We used the National Cancer Data Base to investigate whether there is an association between a ≥ 90-day delay from transurethral resection of bladder tumor (TURBT) in initiating CRT and overall survival. We included patients with cT2-4N0M0 muscle-invasive bladder cancer from 2004 to 2015 who underwent TURBT and curative-intent concurrent CRT. Patients were grouped on the basis of timing of CRT: ≤ 89 days after TURBT (earlier) vs. ≥ 90 and < 180 days after TURBT (delayed).

Results: A total of 1387 (87.5%) received earlier CRT (median, 45 days after TURBT; interquartile range, 34-59 days), and 197 (12.5%) received delayed CRT (median, 111 days after TURBT; interquartile range, 98-130 days). Median overall survival was 29.0 months (95% CI, 26.0-32.0) versus 27.0 months (95% CI, 19.75-34.24) for earlier and delayed CRT (P = .94). On multivariable analysis, delayed CRT was not associated with an overall survival difference (hazard ratio, 1.05; 95% CI, 0.87-1.27; P = .60).

Conclusion: Although these results are limited and require validation, short, strategic treatment delays during a pandemic can be considered on the basis of clinician judgment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clgc.2020.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306737PMC
February 2021

NRG Oncology Updated International Consensus Atlas on Pelvic Lymph Node Volumes for Intact and Postoperative Prostate Cancer.

Int J Radiat Oncol Biol Phys 2021 Jan 27;109(1):174-185. Epub 2020 Aug 27.

Medical College of Wisconsin, Department of Radiation Oncology, Milwaukee, Wisconsin.

Purpose: In 2009, the Radiation Therapy Oncology Group (RTOG) genitourinary members published a consensus atlas for contouring prostate pelvic nodal clinical target volumes (CTVs). Data have emerged further informing nodal recurrence patterns. The objective of this study is to provide an updated prostate pelvic nodal consensus atlas.

Methods And Materials: A literature review was performed abstracting data on nodal recurrence patterns. Data were presented to a panel of international experts, including radiation oncologists, radiologists, and urologists. After data review, participants contoured nodal CTVs on 3 cases: postoperative, intact node positive, and intact node negative. Radiation oncologist contours were analyzed qualitatively using count maps, which provided a visual assessment of controversial regions, and quantitatively analyzed using Sorensen-Dice similarity coefficients and Hausdorff distances compared with the 2009 RTOG atlas. Diagnostic radiologists generated a reference table outlining considerations for determining clinical node positivity.

Results: Eighteen radiation oncologists' contours (54 CTVs) were included. Two urologists' volumes were examined in a separate analysis. The mean CTV for the postoperative case was 302 cm, intact node positive case was 409 cm, and intact node negative case was 342 cm. Compared with the original RTOG consensus, the mean Sorensen-Dice similarity coefficient for the postoperative case was 0.63 (standard deviation [SD] 0.13), the intact node positive case was 0.68 (SD 0.13), and the intact node negative case was 0.66 (SD 0.18). The mean Hausdorff distance (in cm) for the postoperative case was 0.24 (SD 0.13), the intact node positive case was 0.23 (SD 0.09), and intact node negative case was 0.33 (SD 0.24). Four regions of CTV controversy were identified, and consensus for each of these areas was reached.

Conclusions: Discordance with the 2009 RTOG consensus atlas was seen in a group of experienced NRG Oncology and international genitourinary radiation oncologists. To address areas of variability and account for new data, an updated NRG Oncology consensus contour atlas was developed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2020.08.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736505PMC
January 2021

Resolution of a High Grade and Metastatic BK Polyomavirus-Associated Urothelial Cell Carcinoma Following Radical Allograft Nephroureterectomy and Immune Checkpoint Treatment: A Case Report.

Transplant Proc 2020 Nov 30;52(9):2720-2725. Epub 2020 Jul 30.

Department of Surgery/Division of Transplant Surgery, Massachusetts General Hospital, Boston, MA.

Background: BK viral infection in the posttransplant setting continues to cause serious morbidity with effects ranging from allograft nephropathy and dysfunction to urothelial malignancy.

Results: In this report, we present a patient that developed BK-associated nephropathy and, 6 years later, locally advanced urothelial malignancy in the renal allograft with nodal, muscle, and extremity involvement. Following radical allograft nephroureterectomy, he was treated with palliative radiation and the immune checkpoint inhibitor atezolizumab. Follow-up imaging at 1 year demonstrated radiographic complete response.

Conclusions: This report supports the growing body of evidence supporting the association of urothelial malignancy and BK virus infection in renal transplant recipients. Further, it highlights the novel application of immune checkpoint inhibitors in the treatment of advanced posttransplant malignancy, in particular when the allograft is removed and the tumor is possibly of donor origin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.transproceed.2020.06.012DOI Listing
November 2020

Association of the Placement of a Perirectal Hydrogel Spacer With the Clinical Outcomes of Men Receiving Radiotherapy for Prostate Cancer: A Systematic Review and Meta-analysis.

JAMA Netw Open 2020 06 1;3(6):e208221. Epub 2020 Jun 1.

Department of Radiation Oncology, MediClin Robert Janker Klinik, Bonn, Germany.

Importance: Perirectal spacers are intended to lower the risk of rectal toxic effects associated with prostate radiotherapy. A quantitative synthesis of typical clinical results with specific perirectal spacers is limited.

Objective: To evaluate the association between perirectal hydrogel spacer placement and clinical outcomes of men receiving radiotherapy for prostate cancer.

Data Sources: A systematic search was performed of the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for articles published through September 2019.

Study Selection: Studies comparing men who received a hydrogel spacer vs men who did not receive a spacer (controls) prior to prostate radiotherapy.

Data Extraction And Synthesis: Via random-effects meta-analysis, group comparisons were reported using the weighted mean difference for continuous measures and the risk ratio for binary measures.

Main Outcomes And Measures: Procedural results, the percentage volume of rectum receiving at least 70 Gy radiation (v70), early (≤3 months) and late (>3 months) rectal toxic effects, and early and late changes in bowel-related quality of life on the Expanded Prostate Cancer Index Composite (minimal clinically important difference, 4 points).

Results: The review included 7 studies (1 randomized clinical trial and 6 cohort studies) involving 1011 men (486 who received a hydrogel spacer and 525 controls), with a median duration of patient follow-up of 26 months (range, 3-63 months). The success rate of hydrogel spacer placement was 97.0% (95% CI, 94.4%-98.8% [5 studies]), and the weighted mean perirectal separation distance was 11.2 mm (95% CI, 10.1-12.3 mm [5 studies]). Procedural complications were mild and transient, occurring in 0% to 10% of patients within the studies. The hydrogel spacer group received 66% less v70 rectal irradiation compared with controls (3.5% vs 10.4%; mean difference, -6.5%; 95% CI, -10.5% to -2.5%; P = .001 [6 studies]). The risk of grade 2 or higher rectal toxic effects was comparable between groups in early follow-up (4.5% in hydrogel spacer group vs 4.1% in control group; risk ratio, 0.82; 95% CI, 0.52-1.28; P = .38 [6 studies]) but was 77% lower in the hydrogel spacer group in late follow-up (1.5% vs 5.7%; risk ratio, 0.23; 95% CI, 0.06-0.99; P = .05 [4 studies]). Changes in bowel-related quality of life were comparable between groups in early follow-up (mean difference, 0.2; 95% CI, -3.1 to 3.4; P = .92 [2 studies]) but were greater in the hydrogel spacer group in late follow-up (mean difference, 5.4; 95% CI, 2.8-8.0; P < .001 [2 studies]).

Conclusions And Relevance: For men receiving prostate radiotherapy, injection of a hydrogel spacer was safe, provided prostate-rectum separation sufficient to reduce v70 rectal irradiation, and was associated with fewer rectal toxic effects and higher bowel-related quality of life in late follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2020.8221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301230PMC
June 2020

Addition of Androgen-Deprivation Therapy or Brachytherapy Boost to External Beam Radiotherapy for Localized Prostate Cancer: A Network Meta-Analysis of Randomized Trials.

J Clin Oncol 2020 09 12;38(26):3024-3031. Epub 2020 May 12.

Department of Radiation Oncology, University of Michigan, Ann Arbor, MI.

Purpose: In men with localized prostate cancer, the addition of androgen-deprivation therapy (ADT) or a brachytherapy boost (BT) to external beam radiotherapy (EBRT) have been shown to improve various oncologic end points. Practice patterns indicate that those who receive BT are significantly less likely to receive ADT, and thus we sought to perform a network meta-analysis to compare the predicted outcomes of a randomized trial of EBRT plus ADT versus EBRT plus BT.

Materials And Methods: A systematic review identified published randomized trials comparing EBRT with or without ADT, or EBRT (with or without ADT) with or without BT, that reported on overall survival (OS). Standard fixed-effects meta-analyses were performed for each comparison, and a meta-regression was conducted to adjust for use and duration of ADT. Network meta-analyses were performed to compare EBRT plus ADT versus EBRT plus BT. Bayesian analyses were also performed, and a rank was assigned to each treatment after Markov Chain Monte Carlo analyses to create a surface under the cumulative ranking curve.

Results: Six trials compared EBRT with or without ADT (n = 4,663), and 3 compared EBRT with or without BT (n = 718). The addition of ADT to EBRT improved OS (hazard ratio [HR], 0.71 [95% CI, 0.62 to 0.81]), whereas the addition of BT did not significantly improve OS (HR, 1.03 [95% CI, 0.78 to 1.36]). In a network meta-analysis, EBRT plus ADT had improved OS compared with EBRT plus BT (HR, 0.68 [95% CI, 0.52 to 0.89]). Bayesian modeling demonstrated an 88% probability that EBRT plus ADT resulted in superior OS compared with EBRT plus BT.

Conclusion: Our findings suggest that current practice patterns of omitting ADT with EBRT plus BT may result in inferior OS compared with EBRT plus ADT in men with intermediate- and high-risk prostate cancer. ADT for these men should remain a critical component of treatment regardless of radiotherapy delivery method until randomized evidence demonstrates otherwise.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.19.03217DOI Listing
September 2020

Association of Presalvage Radiotherapy PSA Levels After Prostatectomy With Outcomes of Long-term Antiandrogen Therapy in Men With Prostate Cancer.

JAMA Oncol 2020 05;6(5):735-743

Department of Radiation Oncology, University of Michigan, Ann Arbor.

Importance: In men with recurrent prostate cancer, addition of long-term antiandrogen therapy to salvage radiotherapy (SRT) was associated with overall survival (OS) in the NRG/RTOG 9601 study. However, hormone therapy has associated morbidity, and there are no validated predictive biomarkers to identify which patients derive most benefit from treatment.

Objective: To examine the role of pre-SRT prostate-specific antigen (PSA) levels to personalize hormone therapy use with SRT.

Interventions: Men were randomized to SRT plus high-dose nonsteroidal antiandrogen (bicalutamide, 150 mg/d) or placebo for 2 years.

Design, Setting, And Participants: In this secondary analysis of the multicenter RTOG 9601 double-blind, placebo-controlled randomized clinical trial conducted from 1998 to 2003 by a multinational cooperative group, men with a positive surgical margin or pathologic T3 disease after radical prostatectomy with pre-SRT PSA of 0.2 to 4.0 ng/mL were included. Analysis was performed between March 4, 2019, and December 20, 2019.

Main Outcomes And Measures: The primary outcome was overall survival (OS). Secondary end points included distant metastasis (DM), other-cause mortality (OCM), and grades 3 to 5 cardiac and neurologic toxic effects. Subgroup analyses were performed using the protocol-specified PSA stratification variable (1.5 ng/mL) and additional PSA cut points, including test for interaction. Competing risk analyses were performed for DM and other-cause mortality (OCM).

Results: Overall, 760 men with PSA elevation after radical prostatectomy for prostate cancer were included. The median (range) age of particpants was 65 (40-83) years. Antiandrogen assignment was associated with an OS benefit in the PSA stratum greater than 1.5 ng/mL (n = 118) with a 25% 12-year absolute benefit (hazard ratio [HR], 0.45; 95% CI, 0.25-0.81), but not in the PSA of 1.5 ng/mL or less stratum (n = 642) (1% 12-year absolute difference; HR, 0.87; 95% CI, 0.66-1.16). In a subanalysis of men with PSA of 0.61 to 1.5 (n = 253), there was an OS benefit associated with antiandrogen assignment (HR, 0.61; 95% CI, 0.39-0.94). In those receiving early SRT (PSA ≤0.6 ng/mL, n = 389), there was no improvement in OS (HR, 1.16; 95% CI, 0.79-1.70), an increased OCM hazard (subdistribution HR, 1.94; 95% CI, 1.17-3.20; P = .01), and an increased odds of late grades 3 to 5 cardiac and neurologic toxic effects (odds ratio, 3.57; 95% CI, 1.09-15.97; P = .05).

Conclusions And Relevance: These results suggest that pre-SRT PSA level may be a prognostic biomarker for outcomes of antiandrogen treatment with SRT. In patients receiving late SRT (PSA >0.6 ng/mL, hormone therapy was associated with improved outcomes. In men receiving early SRT (PSA ≤0.6 ng/mL), long-term antiandrogen treatment was not associated with improved OS. Future randomized clinical trials are needed to determine hormonal therapy benefit in this population.

Trial Registration: ClinicalTrials.gov Identifier: NCT00002874.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoncol.2020.0109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189892PMC
May 2020

Distribution of Molecular Subtypes in Muscle-invasive Bladder Cancer Is Driven by Sex-specific Differences.

Eur Urol Oncol 2020 08 20;3(4):420-423. Epub 2020 Mar 20.

Department of Urology, University of California San Francisco, San Francisco, CA, USA. Electronic address:

Muscle-invasive bladder cancer (MIBC) is a sex-biased cancer with a higher incidence in men but worse outcomes in women. The root cause behind these observations remains unclear. To investigate whether sex-specific tumor biology could explain the differences in clinical behavior of MIBC, we analyzed the transcriptome profiles from transurethral resected bladder tumors of 1000 patients. Female tumors expressed higher levels of basal- and immune-associated genes, while male tumors expressed higher levels of luminal markers. Using molecular subtyping, we found that the rates of the basal/squamous subtype were higher in females than in males. Males were enriched with tumors of the luminal papillary (LumP) and neuroendocrine-like subtypes. Male MIBC tumors had higher androgen response activity across all luminal subtypes and male patients with LumP tumors were younger. Taken together, these data confirm differences in molecular subtypes based on sex. The role of the androgen response pathway in explaining subtype differences between men and women should be studied further. PATIENT SUMMARY: We explored the sex-specific biology of bladder cancer in 1000 patients and found that women had more aggressive cancer with higher immune activity. Men tended toward less aggressive tumors that showed male hormone signaling, suggesting that male hormones may influence the type of bladder cancer that a patient develops.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.euo.2020.02.010DOI Listing
August 2020

Bladder Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology.

J Natl Compr Canc Netw 2020 03;18(3):329-354

National Comprehensive Cancer Network.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on the clinical presentation and workup of suspected bladder cancer, treatment of non-muscle-invasive urothelial bladder cancer, and treatment of metastatic urothelial bladder cancer because important updates have recently been made to these sections. Some important updates include recommendations for optimal treatment of non-muscle-invasive bladder cancer in the event of a bacillus Calmette-Guérin (BCG) shortage and details about biomarker testing for advanced or metastatic disease. The systemic therapy recommendations for second-line or subsequent therapies have also been revised. Treatment and management of muscle-invasive, nonmetastatic disease is covered in the complete version of the NCCN Guidelines for Bladder Cancer available at NCCN.org. Additional topics covered in the complete version include treatment of nonurothelial histologies and recommendations for nonbladder urinary tract cancers such as upper tract urothelial carcinoma, urothelial carcinoma of the prostate, and primary carcinoma of the urethra.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.6004/jnccn.2020.0011DOI Listing
March 2020

EDITORIAL COMMENT.

Urology 2019 11;133:171-172

Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.urology.2019.05.063DOI Listing
November 2019

Quality Indicators for Bladder Cancer Services: A Collaborative Review.

Eur Urol 2020 07 26;78(1):43-59. Epub 2019 Sep 26.

Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:

Context: There is a lack of accepted consensus on what should constitute appropriate quality-of-care indicators for bladder cancer.

Objective: To evaluate the optimal management of bladder cancer and propose quality indicators (QIs).

Evidence Acquisition: A systematic review was performed to identify literature on current optimal management and potential quality indicators for both non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) bladder cancer. A panel of experts was convened to select a recommended list of QIs.

Evidence Synthesis: For NMIBC, preoperative QIs include tobacco cessation counselling and appropriate imaging before initial transurethral resection of bladder tumour (TURBT). Intraoperative QIs include administration of antibiotics, proper safe conduct of TURBT using a checklist, and performing restaging TURBT with biopsy of the prostatic urethra in appropriate cases. Postoperative QIs include appropriate receipt of perioperative adjuvant therapy, risk-stratified surveillance, and appropriate decision to change therapy when indicated (eg, bacillus Calmette-Guerin [BCG] unresponsive). For MIBC, preoperative QIs include multidisciplinary care, selection for candidates for continent urinary diversion, receipt of neoadjuvant cisplatin-based chemotherapy, time to commencing radical treatment, consideration of trimodal therapy as a bladder-sparing alternative in select patients, preoperative counselling with stoma marking, surgical volume of radical cystectomy, and enhanced recovery after surgery protocols. Intraoperative QIs include adequacy of lymphadenectomy, blood loss, and operative time. Postoperative QIs include prospective standardised monitoring of morbidity and mortality, negative surgical margins for pT2 disease, appropriate surveillance after primary treatment, and adjuvant cisplatin-based chemotherapy in appropriate cases. Participation in clinical trials was highlighted as an important component indicating high quality of care.

Conclusions: We propose a set of QIs for both NMIBC and MIBC based on established clinical guidelines and the available literature. Although there is currently a lack of level 1 evidence for the benefit of implementing these QIs, we believe that the measurement of these QIs could aid in the improvement and benchmarking of optimal care for bladder cancer.

Patient Summary: After a systematic review of existing guidelines and literature, a panel of experts has recommended a set of quality indicators that can help providers and patients measure and strive towards optimal outcomes for bladder cancer care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eururo.2019.09.001DOI Listing
July 2020

Recent Global Patterns in Prostate Cancer Incidence and Mortality Rates.

Eur Urol 2020 01 5;77(1):38-52. Epub 2019 Sep 5.

Surveillance and Health Services Research Program, American Cancer Society, Atlanta, GA, USA.

Context: Previous studies have reported significant variation in prostate cancer rates and trends mainly due to differences in detection practices, availability of treatment, and underlying genetic susceptibility.

Objective: To assess recent worldwide prostate cancer incidence, mortality rates, and trends using up-to-date incidence and mortality data.

Evidence Acquisition: We present estimated age-standardized prostate cancer incidence and mortality rates by country and world regions for 2018 based on the GLOBOCAN database. We also examined rates and temporal trends for incidence (44 countries) and mortality (76 countries) based on data series from population-based registries.

Evidence Synthesis: The highest estimated incidence rates were found in Australia/New Zealand, Northern America, Western and Northern Europe, and the Caribbean, and the lowest rates were found in South-Central Asia, Northern Africa, and South-Eastern and Eastern Asia. The highest estimated mortality rates were found in the Caribbean (Barbados, Trinidad and Tobago, and Cuba), sub-Saharan Africa (South Africa), parts of former Soviet Union (Lithuania, Estonia, and Latvia), whereas the lowest rates were found in Asia (Thailand and Turkmenistan). Prostate cancer incidence rates during the most recent 5 yr declined (five countries) or stabilized (35 countries), after increasing for many years; in contrast, rates continued to increase for four countries in Eastern Europe and Asia. During the most recent 5 data years, mortality rates among the 76 countries examined increased (three countries), remained stable (59 countries), or decreased (14 countries).

Conclusions: As evident from available data, prostate cancer incidence and mortality rates have been on the decline or have stabilized recently in many countries, with decreases more pronounced in high-income countries. These trends may reflect a decline in prostate-specific antigen testing (incidence) and improvements in treatment (mortality).

Patient Summary: We examined recent trends in prostate cancer incidence and mortality rates in 44 and 76 countries, respectively, and found that rates in most countries stabilized or decreased.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eururo.2019.08.005DOI Listing
January 2020

Practice Patterns and Outcomes Among Patients With N0M0 Prostate Cancer and a Very High Prostate-Specific Antigen Level.

J Natl Compr Canc Netw 2019 08;17(8):941-948

Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts.

Background: Management of patients with a very high prostate-specific antigen (PSA) level (≥98.0 ng/mL) but clinically localized (N0M0) prostate cancer is challenging. This study sought to determine practice patterns and outcomes among these patients.

Patients And Methods: A total of 748,825 patients with prostate cancer from 2004 through 2012 were identified using the National Cancer Database. These patients were subdivided by PSA level (0-9.9, 10.0-19.9, 20.0-39.9, 40.0-59.9, 60.0-79.9, 80.0-97.9, and ≥98.0 ng/mL), nodal status (N0 vs N1), and distant metastases (M0 vs M1). Rates of locoregional treatment and 5-year overall survival (OS) in each group were determined. Survival was compared using Cox regression after adjusting for multiple patient-specific factors.

Results: The rate of locoregional treatment for patients with N0M0 disease and PSA level ≥98.0 ng/mL was significantly lower than for those with N1M0 disease (52.6% vs 60.4%; P<.001) or N0M0 disease and PSA level <98.0 ng/mL (52.6% vs 86.6%; P<.001). The 5-year OS rate was similar for patients with N1M0 disease and those with N0M0 disease and a very high PSA level (63.2% vs 59.1%; adjusted hazard ratio [aHR], 0.91; P=.063). The survival benefit associated with locoregional treatment was higher among those with N0M0 disease and a very high PSA level than among those with N1M0 disease (aHR, 0.28 vs 0.44; P<.001).

Conclusions: Patients with clinical N0M0 disease and a very high PSA level (≥98.0 ng/mL) have outcomes similar to those with N1 disease but receive locoregional treatment at a lower rate. Future work is needed to investigate the utility of locoregional treatment in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.6004/jnccn.2018.7283DOI Listing
August 2019

Explaining disparities in oncology health systems delays and stage at diagnosis between men and women in Botswana: A cohort study.

PLoS One 2019 6;14(6):e0218094. Epub 2019 Jun 6.

Harvard Medical School, Boston, Massachusetts, United States of America.

Purpose: Men in Botswana present with more advanced cancer than women, leading to poorer outcomes. We sought to explain sex-specific differences in time to and stage at treatment initiation.

Methods: Cancer patients who initiated oncology treatment between October 2010 and June 2017 were recruited at four oncology centers in Botswana. Primary outcomes were time from first visit with cancer symptom to treatment initiation, and advanced cancer (stage III/IV). Sociodemographic and clinical covariates were obtained retrospectively through interviews and medical record review. We used accelerated failure time and logistic models to estimate standardized sex differences in treatment initiation time and risk differences for presentation with advanced stage. Results were stratified by cancer type (breast, cervix, non-Hodgkin's lymphoma, anogenital, head and neck, esophageal, other).

Results: 1886 participants (70% female) were included. After covariate adjustment, men experienced longer excess time from first presentation to treatment initiation (8.4 months) than women (7.0 months) for all cancers combined (1.4 months, 95% CI: 0.30, 2.5). In analysis stratified by cancer type, we only found evidence of a sex disparity (Men: 8.2; Women: 6.8 months) among patients with other, non-common cancers (1.4 months, 95% CI: 0.01, 2.8). Men experienced an increased risk of advanced stage (Men: 67%; Women: 60%; aRD: 6.7%, 95% CI: -1.7%, 15.1%) for all cancers combined, but this disparity was only statistically significant among patients with anogenital cancers (Men: 72%; Women: 50%; aRD: 22.0%, 95% CI: 0.5%, 43.5%).

Conclusions: Accounting for the types of cancers experienced by men and women strongly attenuated disparities in time to treatment initiation and stage. Higher incidence of rarer cancers among men could explain these disparities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218094PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553768PMC
February 2020

The current state of randomized clinical trial evidence for prostate brachytherapy.

Urol Oncol 2019 09 3;37(9):599-610. Epub 2019 May 3.

Department of Radiation Oncology, University of Michigan, Ann Arbor, MI.

Interstitial brachytherapy is one of several curative therapeutic options for the treatment of localized prostate cancer. In this review, we summarize all available randomized data to support the optimal use of prostate brachytherapy. Evidence from completed randomized controlled trials is the focus of this review with a presentation also of important ongoing trials. Gaps in knowledge are identified where future investigation may be fruitful with intent to inspire well-designed prospective studies with standardized treatment that focuses on improving oncological outcomes, reducing morbidity, or maintaining quality of life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.urolonc.2019.04.009DOI Listing
September 2019

Proton versus photon-based radiation therapy for prostate cancer: emerging evidence and considerations in the era of value-based cancer care.

Prostate Cancer Prostatic Dis 2019 12 9;22(4):509-521. Epub 2019 Apr 9.

Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Background: Advances in radiation technology have transformed treatment options for patients with localized prostate cancer. The evolution of three-dimensional conformal radiation therapy and intensity-modulated radiation therapy (IMRT) have allowed physicians to spare surrounding normal organs and reduce adverse effects. The introduction of proton beam technology and its physical advantage of depositing its energy in tissue at the end-of-range maximum may potentially spare critical organs such as the bladder and rectum in prostate cancer patients. Data thus far are limited to large, observational studies that have not yet demonstrated a definite benefit of protons over conventional treatment with IMRT. The cost of proton beam treatment adds to the controversy within the field.

Methods: We performed an extensive literature review for all proton treatment-related prostate cancer studies. We discuss the history of proton beam technology, as well as its role in the treatment of prostate cancer, associated controversies, novel technology trends, a discussion of cost-effectiveness, and an overview of the ongoing modern large prospective studies that aim to resolve the debate between protons and photons for prostate cancer.

Results: Present data have demonstrated that proton beam therapy is safe and effective compared with the standard treatment options for prostate cancer. While dosimetric studies suggest lower whole-body radiation dose and a theoretically higher relative biological effectiveness in prostate cancer compared with photons, no studies have demonstrated a clear benefit with protons.

Conclusions: Evolving trends in proton treatment delivery and proton center business models are helping to reduce costs. Introduction of existing technology into proton delivery allows further control of organ motion and addressing organs-at-risk. Finally, the much-awaited contemporary studies comparing photon with proton-based treatments, with primary endpoints of patient-reported quality-of-life, will help us understand the differences between proton and photon-based treatments for prostate cancer in the modern era.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41391-019-0140-7DOI Listing
December 2019

Molecular Characterization of Neuroendocrine-like Bladder Cancer.

Clin Cancer Res 2019 07 5;25(13):3908-3920. Epub 2019 Apr 5.

Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.

Purpose: Neuroendocrine (NE) bladder carcinoma is a rare and aggressive variant. Molecular subtyping studies have found that 5% to 15% of muscle-invasive bladder cancer (MIBC) have transcriptomic patterns consistent with NE bladder cancer in the absence of NE histology. The clinical implications of this NE-like subtype have not been explored in depth.

Experimental Design: Transcriptome-wide expression profiles were generated for MIBC collected from 7 institutions and clinical-use of Decipher Bladder. Using unsupervised clustering, we generated a clustering solution on a prospective training cohort (PTC; = 175), developed single-sample classifiers to predict NE tumors, and evaluated the resultant models on a testing radical cystectomy (RC) cohort ( = 225). A random forest model was finalized and applied to 5 validation cohorts ( = 1302). Uni- and multivariable survival analyses were used to characterize clinical outcomes.

Results: In the training cohort (PTC), hierarchical clustering using an 84-gene panel showed a cluster of 8 patients (4.6%) with highly heterogeneous expression of NE markers in the absence of basal or luminal marker expression. NE-like tumors were identified in 1% to 6.6% of cases in validation cohorts. Patients with NE-like tumors had significantly worse 1-year progression-free survival (65% NE-like vs. 82% overall; = 0.046) and, after adjusting for clinical and pathologic factors, had a 6.4-fold increased risk of all-cause mortality ( = 0.001). IHC confirmed the neuronal character of these tumors.

Conclusions: A single-patient classifier was developed that identifies patients with histologic urothelial cancer harboring a NE transcriptomic profile. These tumors represent a high-risk subgroup of MIBC, which may require different treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-18-3558DOI Listing
July 2019

Combining Immunotherapy with Radiotherapy for the Treatment of Genitourinary Malignancies.

Eur Urol Oncol 2019 02 16;2(1):79-87. Epub 2018 Nov 16.

Department of Radiation Oncology, Weill Cornell Medicine, New York, NY, USA.

Context: Immunotherapy drugs, particularly checkpoint inhibitors, have recently been approved by the Food and Drug Administration for various malignancies. Preclinical and early clinical data show that combining these agents with radiotherapy may produce an even more potent antitumor effect in the treatment of cancer.

Objective: To describe the rationale, available data, and emerging data on the use of combined immunotherapy and radiation therapy in the setting of genitourinary (GU) malignancies.

Evidence Acquisition: We performed a search of primary studies from PubMed/Medline that included combinations of the search terms "radiation therapy," "radiotherapy," "abscopal effect," "immunotherapy," "combined," and "combination."

Evidence Synthesis: Preclinical and clinical data support both immune-stimulating and immune-suppressing effects of radiotherapy. Preclinical and clinical studies investigating the combination of radiotherapy with immunotherapy, primarily in the setting of non-GU malignancies, have suggested efficacy and tolerability. Early randomized trials combining radiotherapy and immunotherapy have demonstrated success in lung cancer. Although a trial investigating combined immunotherapy and radiotherapy use for prostate cancer did not clearly improve survival, trials are ongoing in multiple GU malignancies to identify synergy between immunotherapy and radiotherapy. Several practical and technical questions remain about the optimal combination of radiotherapy and immunotherapy.

Conclusions: Preclinical and clinical trials show that the combination of the immunotherapy and radiation therapy has the potential to provide a synergistic effect in treating cancer, including GU malignancies, although more work is needed to uncover the mechanism and determine the optimal delivery of this treatment.

Patient Summary: This paper reviews evidence that immunotherapy drugs can be given together with radiation therapy to improve outcomes in cancers of the genitourinary tract. We find promising initial results and raise important questions that need to be answered before this type of treatment can be utilized successfully.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.euo.2018.09.013DOI Listing
February 2019

Editorial comment.

Urology 2019 Feb;124:189-190

Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.urology.2018.07.060DOI Listing
February 2019

Impact of Immune and Stromal Infiltration on Outcomes Following Bladder-Sparing Trimodality Therapy for Muscle-Invasive Bladder Cancer.

Eur Urol 2019 07 1;76(1):59-68. Epub 2019 Feb 1.

Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Massachusetts General Hospital Cancer Center, Boston, MA, USA.

Background: Bladder-sparing trimodality therapy (TMT) is an alternative to radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC), and biomarkers to inform therapy selection are needed.

Objective: To evaluate the prognostic value of immune and stromal signatures in MIBC treated with TMT.

Design, Setting, And Participants: We used a clinical-grade platform to perform transcriptome-wide gene expression profiling of primary tumors from 136 MIBC patients treated with TMT at a single institution. We observed 60 overall survival events at 5yr, and median follow-up time for patients without an event was 5.0yr (interquartile range 3.1, 5.0). Expression data from another cohort of 223 MIBC patients treated with neoadjuvant chemotherapy (NAC) and RC were also analyzed.

Outcome Measurements And Statistical Analysis: Molecular subtype, immune, and stromal signatures were evaluated for associations with disease-specific survival (DSS) and overall survival (OS) in TMT patients, and in patients treated with NAC and RC.

Results And Limitations: Gene expression profiling of TMT cases identified luminal (N=40), luminal-infiltrated (N=26), basal (N=54), and claudin-low (N=16) subtypes. Signatures of T-cell activation and interferon gamma signaling were associated with improved DSS in the TMT cohort (hazard ratio 0.30 [0.14-0.65], p=0.002 for T cells), but not in the NAC and RC cohort. Conversely, a stromal signature was associated with worse DSS in the NAC and RC cohort (p=0.006), but not in the TMT cohort. This study is limited by its retrospective nature.

Conclusions: Higher immune infiltration in MIBC is associated with improved DSS after TMT, whereas higher stromal infiltration is associated with shorter DSS after NAC and RC. Additional studies should be conducted to determine whether gene expression profiling can predict treatment response.

Patient Summary: We used gene expression profiling to study the association between tumor microenvironment and outcomes following bladder preservation therapy for invasive bladder cancer. We found that outcomes varied with immune and stromal signatures within the tumor. We conclude that gene expression profiling has potential to guide treatment decisions in bladder cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eururo.2019.01.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571058PMC
July 2019

SIU-ICUD consultation on bladder cancer: treatment of muscle-invasive bladder cancer.

World J Urol 2019 Jan 25;37(1):61-83. Epub 2019 Jan 25.

Department of Urology, University of Tübingen, Tübingen, Germany.

Purpose: To provide a comprehensive overview and update of the Joint Société Internationale d'Urologie-International Consultation on Urological Diseases (SIU-ICUD) Consultation on Bladder Cancer for muscle-invasive presumably node-negative bladder cancer (MIBC).

Methods: Contemporary literature was analyzed for the latest evidence in treatment options, outcomes, including radical surgery, neoadjuvant and adjuvant treatment modalities, and bladder-sparing approaches. An international multi-disciplinary expert panel evaluated and graded the data according to guidelines from the Oxford Centre for Evidence-Based Medicine.

Results: Radical cystectomy (RC) is the standard of care for MIBC patients considered to be surgical candidates. While associated with substantial morbidity and mortality, this has been mitigated with improved technique, minimally invasive technology, and better perioperative care pathways (e.g., enhanced recovery after surgery). Neoadjuvant (NA) cisplatin-based combination chemotherapy improves overall survival and should be offered to eligible ≥ cT2N0 patients. Adjuvant (Adj) cisplatin-based combination chemotherapy may be considered, particularly for pT3-4 and/or pN+ disease without prior NA chemotherapy. Trimodal bladder-preserving treatment via maximum transurethral resection of bladder tumor followed by concurrent chemoradiation is safe and, when combined with early salvage RC for recurrence, offers long-term survival rates in selected patients comparable to RC. Immunotherapy is still experimental and is given either alone or in combination with chemotherapy and/or radiation.

Conclusion: A multi-disciplinary approach is paramount to achieving optimal outcomes for MIBC patients, irrespective of their age, performance and nutritional status, fitness/frailty, renal and other organ function, or disease severity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00345-018-2606-yDOI Listing
January 2019

Active Surveillance of Prostate Cancer is a Viable Option for Men Younger than 60 Years.

J Urol 2019 04;201(4):721-727

Department of Urology, Harvard Medical School , Boston , Massachusetts.

Purpose: At most centers strict age criteria are lacking for eligibility for active surveillance of prostate cancer. Younger men are often counseled to undergo definitive treatment despite limited data on the outcomes of active surveillance in younger men. We compared clinical characteristics and outcomes in men who enrolled in active surveillance at age less than 60 vs 60 years old or older.

Materials And Methods: We retrospectively reviewed the records of 2 institutional cohorts of a total of 2,084 men in whom prostate cancer was managed by active surveillance between 1995 and 2016. We compared outcomes in men who began active surveillance at age 60 vs 60 years or older using the Kaplan-Meier method and Cox proportional hazards regression.

Results: We identified 417 and 1,667 men who began active surveillance at younger than 60 and 60 years old or older, respectively, who met study inclusion criteria. At a median followup of 6.2 years we found no significant difference between men younger than 60 and 60 years old or older in the 5-year rates of biopsy progression-free survival (83% vs 83%), treatment-free survival (74% vs 71%), metastasis-free survival (99.7% vs 99.0%) or prostate cancer specific survival (100% vs 99.7%). Of the younger men 131 (31%) ultimately underwent treatment, including for pathological progression in 67% and prostate specific antigen progression in 18%. On multivariate analysis significant predictors of biopsy progression and progression to treatment among younger men were 20% or greater involvement of any core on diagnostic biopsy (HR 2.21, p = 0.003) and prostate specific antigen density 0.15 ng/ml/ml or greater (HR 1.93, p = 0.01).

Conclusions: Active surveillance is a viable option in select men younger than 60 years with low volume, low risk prostate cancer. However, patients must be surveyed closely and understand the significant likelihood of ultimately requiring treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JU.0000000000000031DOI Listing
April 2019

Safeguarding Autonomy of Patients With Bladder Cancer.

Int J Radiat Oncol Biol Phys 2019 01 12;103(1):81-83. Epub 2018 Dec 12.

Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2018.07.2019DOI Listing
January 2019

Proton therapy for prostate cancer: A review of the rationale, evidence, and current state.

Urol Oncol 2019 09 4;37(9):628-636. Epub 2018 Dec 4.

Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.

Men diagnosed with localized prostate cancer have many curative treatment options including several different radiotherapeutic approaches. Proton radiation is one such radiation treatment modality and, due to its unique physical properties, offers the appealing potential of reduced side effects without sacrificing cancer control. In this review, we examine the intriguing dosimetric rationale and theoretical benefit of proton radiation for prostate cancer and highlight the results of preclinical modeling studies. We then discuss the current state of the clinical evidence for proton efficacy and toxicity, derived from both large claim-based datasets and prospective patient-reported data. The result is that the data are mixed, and clinical equipoise persists in this area. We place these studies into context by summarizing the economics of proton therapy and the changing practice patterns of prostate proton irradiation. Finally, we await the results of a large prospective randomized clinical trial currently accruing and also a large prospective pragmatic comparative study which will provide more rigorous evidence regarding the clinical and comparative effectiveness of proton therapy for prostate cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.urolonc.2018.11.012DOI Listing
September 2019

Molecular biomarkers in bladder preservation therapy for muscle-invasive bladder cancer.

Lancet Oncol 2018 12;19(12):e683-e695

Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA. Electronic address:

Although muscle-invasive bladder cancer is commonly treated with radical cystectomy, a standard alternative is bladder preservation therapy, consisting of maximum transurethral bladder tumour resection followed by radiotherapy with concurrent chemotherapy. Although no successfully completed randomised comparisons are available, the two treatment paradigms seem to have similar long-term outcomes; however, clinicopathologic parameters can be insufficient to provide clear guidance in the selection of one treatment over the other. Recent advances in the molecular understanding of bladder cancer have led to the identification of new predictive biomarkers that ultimately might help guide the tailored selection of therapy on the basis of the intrinsic biology of the tumour. In this Review, we discuss the existing evidence for molecular alterations and genomic signatures as prognostic or predictive biomarkers for bladder preservation therapy. If validated in prospective clinical trials, such biomarkers could enable the identification of subgroups of patients who are more likely to benefit from one treatment over another, and guide the use of combination therapies that include other modalities, such as immunotherapy, which might act synergistically with radiotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1470-2045(18)30693-4DOI Listing
December 2018

Long-term impact of a faculty mentoring program in academic medicine.

PLoS One 2018 29;13(11):e0207634. Epub 2018 Nov 29.

Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.

The authors conducted a prospective longitudinal study from 2009 to 2016 to assess the short and long-term impact of a formal mentorship program on junior faculty satisfaction and productivity. Junior faculty mentees enrolled in the program and junior faculty without formal mentorship were administered surveys before and after the program to assess satisfaction with their mentoring experiences. Long-term retention, promotion, and funding data were also collected. Twenty-three junior faculty mentees and 91 junior faculty controls were included in the study. Mentees came from the Departments of Radiation Oncology and Anesthesia, Critical Care, and Pain Management. After participating in the mentorship program, mentees demonstrated an increase in satisfaction from baseline in five of seven domains related to mentoring, while controls experienced no significant change in satisfaction in six of the seven domains. At long-term follow up, mentees were more likely than controls to hold senior faculty positions (percent senior faculty: 47% vs. 13%, p = 0.030) despite no difference in initial administrative rank. When comparing the subset of faculty who were Instructors at baseline, mentees were more likely to be funded and/or promoted than controls (p = 0.030). A majority of mentees reported that the program strengthened their long-term success, and many maintained their original mentoring relationships and formed new ones, highlighting the strong culture of mentorship that was instilled. Several short-term and long-term benefits were fostered from this formal mentorship program. These findings highlight the potential impact of mentorship programs in propagating a culture of mentorship and excellence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0207634PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6264475PMC
April 2019