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NCCN Guidelines® Insights: Prostate Cancer, Version 1.2023

Featured Updates to the NCCN Guidelines

Edward M. Schaeffer, Sandy Srinivas, Nabil Adra, Yi An, Daniel Barocas, Rhonda Bitting, Alan Bryce, Brian Chapin, Heather H. Cheng, Anthony Victor D’Amico, Neil Desai, Tanya Dorff, James A. Eastham, Thomas A. Farrington, Xin Gao, Shilpa Gupta, Thomas Guzzo, Joseph E. Ippolito, Michael R. Kuettel, Joshua M. Lang, Tamara Lotan, Rana R. McKay, Todd Morgan, George Netto, Julio M. Pow-Sang, Robert Reiter, Mack Roach III, Tyler Robin, Stan Rosenfeld, Ahmad Shabsigh, Daniel Spratt, Benjamin A. Teply, Jonathan Tward, Richard Valicenti, Jessica Karen Wong, Ryan A. Berardi, Dorothy A. Shead, and Deborah A. Freedman-Cass

The NCCN Guidelines for Prostate Cancer address staging and risk assessment after a prostate cancer diagnosis and include management options for localized, regional, recurrent, and metastatic disease. The NCCN Prostate Cancer Panel meets annually to reevaluate and update their recommendations based on new clinical data and input from within NCCN Member Institutions and from external entities. These NCCN Guidelines Insights summarizes much of the panel’s discussions for the 4.2022 and 1.2023 updates to the guidelines regarding systemic therapy for metastatic prostate cancer.

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Daneng Li, Can-Lan Sun, Heeyoung Kim, Christiana Crook, Ya-Han Zhang, Rebecca Allen, Richard Ballena, Shadman Hyder, Marianna Koczywas, Vincent Chung, Dean Lim, Vani Katheria, William Dale, and Gagandeep Singh

Background: Patient preferences (quantity vs quality of life; present vs future health) have not been investigated in patients with neuroendocrine tumors (NETs). The goal of this cross-sectional study was to evaluate patient values toward treatment goals and competing health outcomes among adults with NETs. Patients and Methods: Patients with well-differentiated, grade 1 or 2, advanced NETs starting a new systemic therapy completed 4 tools: (1) Health Outcomes Tool, which ranks the importance of 4 outcomes (survival, function/independence, freedom from pain, freedom from symptoms); (2) Attitude Scale, which identifies the extent to which patients agree with statements related to health outcomes; (3) Now versus Later Tool, which ranks the relative importance of quality of life (QoL) now versus 1 and 5 years from now; and (4) Prognosis and Treatment Perceptions Questionnaire, which identifies the amount of information the patient prefers to receive about their disease and treatment, the patient’s treatment goal, the patient’s perception of the physician’s treatment goal, and self-reported health status. Results: We recruited 60 patients with NETs (50.0% aged ≥65 years; 96.7% with stage IV disease). Primary tumor locations included the gastrointestinal tract (41.7%), pancreas (30.0%), and lung (21.7%). A plurality of patients reported maintaining independence as their most important health outcome (46.7%), followed by survival (30.0%), freedom from pain (11.7%), and freedom from symptoms (11.7%). A total of 67% of patients agreed with the statement, “I would rather live a shorter life than lose my ability to take care of myself”; 85.0% agreed with the statement, “It is more important to me to maintain my thinking ability than to live as long as possible.” When asked to choose between current QoL versus QoL 1 year or 5 years in the future as more important, 48.3% and 40.0% of patients valued their QoL 1 year and 5 years in the future, respectively, more than their current QoL. Only 51.7% of patients believed their physician’s treatment goals aligned with their own. Conclusions: Adult patients with NETs strongly value independence over survival. More communication between patients with NETs and their physicians is needed to ensure that patient preferences are incorporated into treatment plans.

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Christina Teng, Venkatesha, Prunella L. Blinman, and Janette L. Vardy

Background: Chemotherapy-induced peripheral neuropathy (CIPN) can be a debilitating toxicity of oxaliplatin used for treatment of colorectal cancer (CRC). We aimed to assess CIPN symptoms and associations in our colorectal survivorship population and review the impact of neurotoxicity on dose delivery of oxaliplatin. Patients and Methods: Patients attending their first visit to the Sydney Cancer Survivorship Centre following completion of adjuvant treatment for CRC completed comprehensive patient-reported outcome measures, including symptoms, quality of life (QoL), alcohol intake, and exercise habits. Participants scored symptoms of “numbness or pins and needles” in hands or feet from 0 (no trouble at all) to 10 (worst I can imagine). Diagnosis, treatment, and comorbidity details were obtained from medical records. A subset of patients completed serial assessments of PN symptoms at follow-up visits. Results: Data were analyzed from 233 patients (52% male; mean age, 63 years) with CRC attending their first visit at the Sydney Cancer Survivorship Centre. A subset of 104 patients were included in the longitudinal analysis. The odds of patient-reported numbness were significantly higher in patients receiving oxaliplatin (odds ratio, 5.6; 95% CI, 3.2–9.8), with 72.4% of oxaliplatin-treated CRC survivors reporting numbness an average of 5.9 months after chemotherapy. Mean patient-reported numbness was significantly higher in those who received oxaliplatin-containing chemotherapy (mean, 3.31) compared with fluoropyrimidines alone (mean, 1.37) and no chemotherapy (mean, 0.66). Of the patients receiving oxaliplatin, 80% required dose reduction or early cessation, with PN the most common reason reported. QoL in physical, emotional, and functional well-being domains was lower in patients with numbness. We found a weak negative association between numbness score and age, and between (1) numbness and cardiovascular disease and (2) numbers and pain score. Conclusions: CIPN symptoms are common in CRC survivors who have received oxaliplatin and are associated with lower QoL. Neurotoxicity is underreported in clinical trials compared with real-world populations and is a major barrier to oxaliplatin treatment delivery.

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Amar Gajjar, Anita Mahajan, Mohamed Abdelbaki, Clarke Anderson, Reuben Antony, Tejus Bale, Ranjit Bindra, Daniel C. Bowers, Kenneth Cohen, Bonnie Cole, Kathleen Dorris, Ralph Ermoian, Andrea Franson, Jeffrey Helgager, Daniel Landi, Chi Lin, Laura Metrock, Ronica Nanda, Joshua Palmer, Sonia Partap, Ashley Plant, Sumit Pruthi, Renee Reynolds, Paul Ruggieri, Duncan Stearns, Phillip Storm, Anthony Wang, Katherine Warren, Nicholas Whipple, Wafik Zaky, Nicole R. McMillian, and Lenora A. Pluchino

Central nervous system (CNS) cancers account for approximately one quarter of all pediatric tumors and are the leading cause of cancer-related death in children. More than 4,000 brain and CNS tumors are diagnosed each year in children and teens, and the incidence rate has remained stagnant in recent years. The most common malignant pediatric CNS tumors are gliomas, embryonal tumors consisting of predominately medulloblastomas, and germ cell tumors. The inaugural version of the NCCN Guidelines for Pediatric Central Nervous System Cancers focuses on the diagnosis and management of patients with pediatric diffuse high-grade gliomas. The information contained in the NCCN Guidelines is designed to help clinicians navigate the complex management of pediatric patients with diffuse high-grade gliomas. The prognosis for these highly aggressive tumors is generally poor, with 5-year survival rates of <20% despite the use of combined modality therapies of surgery, radiation therapy and systemic therapy. Recent advances in molecular profiling has expanded the use of targeted therapies in patients whose tumors harbor certain alterations. However, enrollment in a clinical trial is the preferred treatment for eligible patients.

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Ahmed Bilal Khalid, Gerardo Calderon, Shadia I. Jalal, and Greg A. Durm

Background: Immune checkpoint inhibitors (ICIs) have been proven to be very effective in the treatment of multiple cancers. They have a unique side-effect profile distinct from conventional chemotherapy that can manifest as immune-related adverse events (irAEs). With expanding ICI use, clinicians will increasingly encounter irAEs, and thus adequate physician knowledge on their recognition and management is crucial. Methods: To assess physician knowledge of irAEs due to ICIs, an online survey was administered to resident physicians in internal medicine (IM), emergency medicine, and family medicine (FM), as well as to faculty physicians in IM and FM. Results: We sent the survey to 413 physicians and received responses from 155 (38%), of which 110 were residents and 45 were faculty. Pembrolizumab was identified as an ICI by 79% of physicians, nivolumab by 64%, and ipilimumab by 55%. Twenty-five percent incorrectly thought infliximab and adalimumab were ICIs. Most physicians (93%) were able to identify the gastrointestinal tract as an irAE site, whereas only 57% and 67% were able to identify cardiovascular and renal systems as irAE sites, respectively. A total of 59% believed steroids negatively affect efficacy of ICIs and should be used with caution to treat irAEs, 65% incorrectly thought endocrinopathies due to irAEs are usually reversible, and 45% of FM residents considered antibiotics as the mainstay of treatment in ICI-mediated colitis. On a self-rated scale from 0 to 100, the median comfort level for all physicians in recognizing irAEs was 15 and for treatment of irAEs was 10. Conclusions: Significant knowledge gaps exist among residents and faculty physicians across multiple specialties regarding the recognition and treatment of irAEs due to ICIs. Given that these physicians are usually the first point of contact with patients, physician education on identification and treatment of irAEs is needed. Early detection of these toxicities is critical for their resolution.

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Amy E. DeZern and Peter L. Greenberg

Several major updates have recently occurred for the NCCN Guidelines for Myelodysplastic Syndromes (MDS) based on a number of prominent articles that have particular clinical and biologic impact for the field. These changes, which have been included in the current iteration of the NCCN Guidelines (Version 1.2023), include the WHO 2022 classification of MDS as well as the ICC suggestions for same. In addition, the molecular underpinning of MDS has been greatly updated with the generation of the Molecular International Prognostic Scoring System (IPSS-M) and an improved understanding to the prognostic implications of mutated TP53 subtypes, which are additive to the revised IPSS (IPSS-R) for stratification and management of patients with MDS. This report emphasizes the major components of the relevant changes to serve as a guide for therapeutic decision-making for patients with MDS.

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Kedar S. Kirtane, Mohammad U. Zahid, Heiko Enderling, and Louis B. Harrison

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Yuqi Zhang, Marcelo Cerullo, Andrew Esposito, and Vishnukamal Golla

Background: Cancer center accreditation status is predicated on several factors that measure high-value healthcare. However, price transparency, which is critical in healthcare decisions, is not a quality measure included for accreditation. We reported the rates of price disclosure of surgical procedures for 5 cancers (breast, lung, cutaneous melanoma, colon, and prostate) among hospitals ranked by the American College of Surgeon’s Commission on Cancer (ACS-CoC). Methods: We identified nonfederal, adult, and noncritical access ACS-CoC accredited hospitals and used the commercial Turquoise Health database to perform a cross-sectional analysis of hospital price disclosures for 5 common oncologic procedures (mastectomy, lobectomy, wide local excision for cutaneous melanoma, partial colectomy, prostatectomy). Publicly available financial reporting data were used to compile facility-specific features, including bed size, teaching status, Centers for Medicare & Medicaid wage index, and patient revenues. Modified Poisson regression evaluated the association between price disclosure and ACS-CoC accreditation after adjusting for hospital financial performance. Results: Of 1,075 total ACS-CoC accredited hospitals, 544 (50.6%) did not disclose prices for any of the surgical procedures and only 313 (29.1%) hospitals reported prices for all 5 procedures. Of the 5 oncologic procedures, prostatectomy and lobectomy had the lowest price disclosure rates. Disclosing and nondisclosing hospitals significantly differed in ACS-CoC accreditation, ownership type, and teaching status. Hospitals that disclosed prices were more likely to receive Medicaid disproportionate share hospital payments, have lower average charge to cost ratios (4.53 vs 5.15; P<.001), and have lower net hospital margins (−2.03 vs 0.44; P=.005). After adjustment, a 1-point increase in markup was associated with a 4.8% (95% CI, 2.2%–7.4%; P<.001) higher likelihood of nondisclosure. Conclusions: More than half of the hospitals did not disclose prices for any of the 5 most common oncologic procedures despite ACS-CoC accreditation. It remains difficult to obtain price transparency for common oncologic procedures even at centers of excellence, signaling a discordance between quality measures visible to patients.