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.
Thomas W. Flaig, Philippe E. Spiess, Neeraj Agarwal, Rick Bangs, Stephen A. Boorjian, Mark K. Buyyounouski, Sam Chang, Tracy M. Downs, Jason A. Efstathiou, Terence Friedlander, Richard E. Greenberg, Khurshid A. Guru, Thomas Guzzo, Harry W. Herr, Jean Hoffman-Censits, Christopher Hoimes, Brant A. Inman, Masahito Jimbo, A. Karim Kader, Subodh M. Lele, Jeff Michalski, Jeffrey S. Montgomery, Lakshminarayanan Nandagopal, Lance C. Pagliaro, Sumanta K. Pal, Anthony Patterson, Elizabeth R. Plimack, Kamal S. Pohar, Mark A. Preston, Wade J. Sexton, Arlene O. Siefker-Radtke, Jonathan Tward, Jonathan L. Wright, Lisa A. Gurski and Alyse Johnson-Chilla
Megan Randall, Kelly Burgess, Lela Buckingham and Lydia Usha
PARP inhibitors are known to be effective in patients with ovarian cancer (OC) and germline mutations in BRCA1 and BRCA2 genes (BRCA mutations). Little is known, however, about any correlation between the deletion size and location of the BRCA mutation and the response to PARP inhibitors. Women with OC commonly undergo genetic testing because the presence of a germline BRCA mutation impacts therapeutic decisions and is important for cancer surveillance in patients and their family members. This report presents a case of a rare entire germline BRCA1 gene deletion and an exceptional response to a PARP inhibitor, olaparib, in a heavily pretreated patient with OC. Her disease course was also remarkable for complete responses to platinum-based chemotherapy and long chemotherapy-free intervals. Interestingly, the deletion of the entire BRCA1 gene was found after previously negative BRCA test results and is associated with a deletion of 6 adjacent genes without known clinical significance. She has remained progression-free and asymptomatic for >3 years on olaparib, with an overall survival of >12 years. We postulate that this unusually favorable response and prolonged overall survival is related to the cancer cells’ inability to reverse the entire gene deletion to wild-type (a common mechanism of resistance to PARP inhibition). This case shows the value of genetic testing for patients with OC and highlights the utility of additional testing with previously negative results and limited genetic testing. It also provides insight into a potential mechanism of an exceptional response to PARP inhibition.
Pooja Ghatalia and Elizabeth R. Plimack
Five new PD-1/PD-L1 checkpoint inhibitors have been approved for the treatment of metastatic urothelial carcinoma (UC): pembrolizumab, atezolizumab, durvalumab, nivolumab, and avelumab. Although cisplatin-based chemotherapy remains the recommended frontline option for cisplatin-eligible patients with metastatic UC, immunotherapy is now an available option in the second-line setting as well as the frontline setting for selected cisplatin-ineligible patients who are either unable to tolerate chemotherapy or PD-L1–positive. This review describes the updated clinical efficacy of these checkpoint inhibitors in the treatment of advanced UC and suggests how they can be sequenced in the context of available chemotherapeutic options.
Estanislao Arana, Francisco M. Kovacs, Ana Royuela, Beatriz Asenjo, Fatima Nagib, Sandra Pérez-Aguilera, María Dejoz, Alberto Cabrera-Zubizarreta, Yolanda García-Hidalgo, Ana Estremera and for the Spanish Back Pain Research Network Task Force for the Improvement of Inter-Disciplinary Management of Spinal Metastasis
Background: MRI is assumed to be valid for distinguishing metastatic vertebral fractures (MVFs) from osteoporotic vertebral fractures (OVFs). This study assessed (1) concordance between the image-based diagnosis of MVF versus OVF and the reference (biopsy or follow-up of >6 months), (2) interobserver and intraobserver agreement on key imaging findings and the diagnosis of MVF versus OVF, and (3) whether disclosing a patient’s history of cancer leads to variations in diagnosis, concordance, or agreement. Patients and Methods: This retrospective cohort study included clinical data and imaging from 203 patients with confirmed MVF or OVF provided to 25 clinicians (neurosurgeons, radiologists, orthopedic surgeons, and radiation oncologists). From January 2018 through October 2018, the clinicians interpreted images in conditions as close as possible to routine practice. Each specialist assessed data twice, with a minimum 6-week interval, blinded to assessments made by other clinicians and to their own previous assessments. The kappa statistic was used to assess interobserver and intraobserver agreement on key imaging findings, diagnosis (MVF vs OVF), and concordance with the reference. Subgroup analyses were based on clinicians’ specialty, years of experience, and complexity of the hospital where they worked. Results: For diagnosis of MVF versus OVF, interobserver agreement was fair, whereas intraobserver agreement was substantial. Only the latter improved to almost perfect when a patient’s history of cancer was disclosed. Interobserver agreement for key imaging findings was fair or moderate, whereas intraobserver agreement on key imaging findings was moderate or substantial. Concordance between the diagnosis of MVF versus OVF and the reference was moderate. Results were similar regardless of clinicians’ specialty, experience, and hospital category. Conclusions: When MRI is used to distinguish MVF versus OVF, interobserver agreement and concordance with the reference were moderate. These results cast doubt on the reliability of basing such a diagnosis on MRI in routine practice.
Featured Updates to the NCCN Guidelines
John A. Thompson, Bryan J. Schneider, Julie Brahmer, Stephanie Andrews, Philippe Armand, Shailender Bhatia, Lihua E. Budde, Luciano Costa, Marianne Davies, David Dunnington, Marc S. Ernstoff, Matthew Frigault, Benjamin H. Kaffenberger, Matthew Lunning, Suzanne McGettigan, Jordan McPherson, Nisha A. Mohindra, Jarushka Naidoo, Anthony J. Olszanski, Olalekan Oluwole, Sandip P. Patel, Nathan Pennell, Sunil Reddy, Mabel Ryder, Bianca Santomasso, Scott Shofer, Jeffrey A. Sosman, Yinghong Wang, Ryan M. Weight, Alyse Johnson-Chilla, Griselda Zuccarino-Catania and Anita Engh
The NCCN Guidelines for Management of Immunotherapy-Related Toxicities provide interdisciplinary guidance on the management of immune-related adverse events (irAEs) resulting from cancer immunotherapy. These NCCN Guidelines Insights describe symptoms that may be caused by an irAE and should trigger further investigation, and summarize the NCCN Management of Immunotherapy-Related Toxicities Panel discussions for the 2020 update to the guidelines regarding immune checkpoint inhibitor–related diarrhea/colitis and cardiovascular irAEs.
William R. Kennedy, Christopher Tricarico, Prashant Gabani, Ashley A. Weiner, Michael B. Altman, Laura L. Ochoa, Maria A. Thomas, Julie A. Margenthaler, Souzan Sanati, Lindsay L. Peterson, Cynthia X. Ma, Foluso O. Ademuyiwa and Imran Zoberi
Background: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC) predicts decreased distant metastasis. However, most patients do not experience pCR, and other risk factors for distant metastasis after NAC are poorly characterized. This study investigated factors predictive of distant metastasis in TNBC without pCR after NAC. Methods: Women with TNBC treated with NAC, surgery, and radiation therapy in 2000 through 2013 were reviewed. Freedom from distant metastasis (FFDM) was compared between patients with and without pCR using the Kaplan-Meier method. In patients without pCR, univariate and multivariable Cox analyses were used to determine factors predictive of distant metastasis. Results: We identified 153 patients with median follow-up of 4.0 years (range, 0.5–14.0 years). After NAC, 108 had residual disease (pCR, 29%). Five-year FFDM was 98% and 55% in patients with and without pCR, respectively (P<.001). Factors independently predicting FFDM in patients without pCR were pathologic nodal positivity (hazard ratio, 3.08; 95% CI, 1.54–6.14; P=.001) and lymphovascular space invasion (hazard ratio, 1.91; 95% CI, 1.07–3.43; P=.030). Patients with a greater number of factors had worse FFDM; 5-year FFDM was 76.5% for patients with no factors (n=38) versus 54.9% and 27.5% for patients with 1 (n=44) and 2 factors (n=26), respectively (P<.001). Conclusions: Lack of pCR after NAC resulted in worse overall survival and FFDM, despite trimodality therapy. In patients with residual disease after NAC, pathologic lymph node positivity and lymphovascular space invasion predicted worse FFDM.
Thomas A. D’Amico, Lindsey A.M. Bandini, Alan Balch, Al B. Benson III, Stephen B. Edge, C. Lyn Fitzgerald, Robert J. Green, Wui-Jin Koh, Michael Kolodziej, Shaji Kumar, Neal J. Meropol, James L. Mohler, David Pfister, Ronald S. Walters and Robert W. Carlson
Although oncology care has evolved, outcome assessment remains a key challenge. Outcome measurement requires identification and adoption of a succinct list of metrics indicative of high-quality cancer care for use within and across healthcare systems. NCCN established an advisory committee, the NCCN Quality and Outcomes Committee, consisting of provider experts from NCCN Member Institutions and other stakeholders, including payers and patient advocacy, community oncology, and health information technology representatives, to review the existing quality landscape and identify contemporary, relevant cancer quality and outcomes measures by reevaluating validated measures for endorsement and proposing new measure concepts to fill crucial gaps. This manuscript reports on 22 measures and concepts; 15 that align with existing measures and 7 that are new.