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Treatment Options for Merkel Cell Carcinoma

Samuel W. Beenken and Marshall M. Urist

Merkel cell carcinoma (MCC) or neuroendocrine carcinoma of the skin is uncommon, often aggressive, and has a poor prognosis. Complete surgical excision with histologic documentation of clear resection margins is recommended for the primary cancer. Retrospective analysis of clinical data strongly suggests that adjuvant radiotherapy improves local control of MCC, but no evidence has been published that it prolongs survival. Sentinel lymph node biopsy is a useful method of determining the need for regional lymph node dissection in stage I patients. Chemotherapy regimens similar to those employed for small cell carcinoma of the lung have been recommended for advanced MCC. Patients often show an initial response to therapy, but it is usually short-lived. The three-year overall survival for patients with MCC is 31%. Before an improvement in long-term survival can be realized, early detection, appropriate use of surgery and radiation therapy, and the development of effective systemic chemotherapy are required.

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Prostate Cancer Clinical Practice Guidelines in Oncology

Although the incidence of prostate cancer has been increasing (1.4% annually from 1995 to 1999), the age-adjusted death rates from prostate cancer have begun to decline (-4.3% annually from 1994 to 1999), and researchers expect prostate cancer to account for only 28,900 deaths in 2003. This suggests that unless prostate cancer is becoming biologically less aggressive, increased public awareness with earlier detection and treatment of prostate cancer has begun to make an impact on this prevalent disease. To properly identify and manage patients with prostate cancer or any malignancy, physicians must have an in-depth understanding of the natural history and treatment options. To this end, an NCCN panel of leading experts from the fields of urology, radiation oncology, and medical oncology at member institutions was appointed to develop guidelines for the treatment of prostate cancer.

For the most recent version of the guidelines, please visit NCCN.org

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Cervical Cancer Screening

Stanford Comprehensive Cancer Center

Cervical carcinoma remains a health issue for women worldwide. Cervical cytology screening is the current method for early detection, and the NCCN Cervical Cancer Screening Clinical Practice Guidelines in Oncology provide direction for evaluating and managing this process, including clarified and revised recommendations on screening techniques and intervals and follow-up of abnormal screening results, including colposcopy. Human papillomavirus (HPV) DNA testing for primary cervical cancer has been approved by the FDA, and HPV DNA testing for high-risk virus types can also be used as a component of both primary screening and workup of abnormal cytology results. Colposcopy, along with colposcopically directed biopsies, has become the primary method for evaluating women with abnormal cervical cytologies. Special considerations for colposcopy performed during pregnancy are also discussed.

For the most recent version of the guidelines, please visit NCCN.org

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Updates on the Management of Immunotherapy-Related Toxicities

Presented by: Marianne Davies, Jordan McPherson, and John A. Thompson

With the increased use of immune checkpoint inhibition (ICI) comes an increase in the number of patients being treated for immune-related adverse events (irAEs). At the NCCN 2023 Annual Conference, presenters discussed 3 different types of irAEs, namely immune-mediated pneumonitis, major adverse cardiac events including myocarditis and myositis/myasthenia gravis overlap syndrome, and oral toxicities including mucositis and sicca syndrome. They emphasized the importance of considering comorbidities and infectious causes when treating immune pneumonitis. In the context of cardiac events during ICI therapy, the presentation highlighted the need for early detection and vigilance in recognizing insidious, nonspecific symptoms, particularly in cases involving myocarditis with myositis/myasthenia gravis overlap syndrome. Finally, the increasing recognition of oral toxicities was discussed, in addition to the importance of timely intervention to prevent long-term morbidity.

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Review of Evidence-Based Support for Pretreatment Imaging in Melanoma

Michael S. Sabel and Sandra L. Wong

Edited by Kerrin G. Robinson

When making a new diagnosis of melanoma, clinicians often obtain imaging studies to rule out clinically occult distant disease. These studies range from inexpensive tests, such as chest radiographs, to more expensive studies, such as PET/CT. The impetus for ordering these studies is usually the desire to identify potentially resectable distant disease, avoid surgery when curative resection is not possible, and assuage patient anxiety by showing that no evidence of distant disease is present. However, some detrimental aspects to these studies are less apparent, including cost and potential for false-positive findings. Although routine use seems reasonable, the true benefit of these studies depends on the probability of clinically occult disease being present, likelihood that disease will be detected with the available technology, and impact of earlier detection on outcome. Contrary to current practice patterns, available evidence suggests that preoperative imaging studies are associated with significant costs and minimal benefit in most patients with melanoma. This article reviews available literature on the role of pretreatment imaging in patients with newly diagnosed cutaneous melanoma.

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International Adaptations of NCCN Clinical Practice Guidelines in Oncology

Robert W. Carlson, Jonathan K. Larsen, Joan McClure, C. Lyn Fitzgerald, Alan P. Venook, Al B. Benson III, and Benjamin O. Anderson

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) are evidence- and consensus-based clinical practice guidelines addressing malignancies that affect more than 97% of all patients with cancer in the United States. The NCCN Guidelines are used extensively in the United States and globally. Use of the guidelines outside the United States has driven the need to adapt the guidelines based on local, regional, or national resources. The NCCN Guidelines Panels created, vetted, and continually update the NCCN Guidelines based on published scientific data on cancer detection, diagnosis, and treatment efficacy. The guidelines are developed within the context of commonly available resources, methods of payment, societal and cultural expectations, and governmental regulations as they exist in the United States. Although many of the cancer management recommendations contained in the NCCN Guidelines apply broadly from a global perspective, not all do. Disparities in availability and access to health care exist among countries, within countries, and among different social groups in the same country, especially regarding resources for cancer prevention, early detection, and treatment. In addition, different drug approval and payment processes result in regional variation in availability of and access to cancer treatment, especially highly expensive agents and radiation therapy. Differences in cancer risk, predictive biomarker expression, and pharmacogenetics exist across ethnic and racial groups, and therefore across geographic locations. Cultural and societal expectations and requirements may also require modification of NCCN Guidelines for use outside the United States. This article describes the adaptation process, using the recent Latin American adaptation of the 2013 NCCN Guidelines for Colorectal Cancer as an example.

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Cancer Type and Risk of Newly Diagnosed Depression Among Elderly Medicare Beneficiaries With Incident Breast, Colorectal, and Prostate Cancers

Monira Alwhaibi, Usha Sambamoorthi, Suresh Madhavan, Thomas Bias, Kimberly Kelly, and James Walkup

Background: Elderly individuals (age >65 years) with cancer are at high risk for newly diagnosed depression after a cancer diagnosis. It is not known whether the risk of newly diagnosed depression varies by cancer type. Purpose: To examine the variations in the risk of newly diagnosed depression by cancer type among elderly individuals with cancer. Methods: This study used a retrospective cohort study design and data from the linked SEER-Medicare files. Elderly individuals (age >65 years) with incident breast, colorectal (CRC), and prostate cancers diagnosed between 2007 and 2011 (N=53,821) were followed for 12 months after cancer diagnosis. Depression diagnosis was identified during the 12-month follow-up period after cancer diagnosis using the ICD-9-Clinical Modification. Complementary log–log regression was used to examine the association between cancer type and risk of newly diagnosed depression after adjusting for other risk factors for depression. Results: We found a significantly higher percentage of newly diagnosed depression among women with CRC compared with those with breast cancer (5.8% vs 3.9%), and among men with CRC compared with those with prostate cancer (3.4% vs 1.6%). In the adjusted analysis, women with CRC had a 28.0% higher risk of newly diagnosed depression compared with women with breast cancer (adjusted risk ratio [ARR], 1.28; 95% CI, 1.12–1.46) and men with CRC had a 104.0% higher risk of newly diagnosed depression compared with those with prostate cancer (ARR, 2.04; 95% CI, 1.65–2.51). Conclusions: Our findings identified cancer types associated with a high risk of newly diagnosed depression after cancer diagnosis, who might benefit from routine depression screening to help in its early detection and treatment.

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Physician Awareness of Immune-Related Adverse Events of Immune Checkpoint Inhibitors

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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Gastroesophageal Cancers: Progress and Problems

Jaffer A. Ajani

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Prognosis of Incidental Brain Metastases in Patients With Advanced Renal Cell Carcinoma

Ritesh R. Kotecha, Ronan Flippot, Taylor Nortman, Annalisa Guida, Sujata Patil, Bernard Escudier, Robert J. Motzer, Laurence Albiges, and Martin H. Voss

Background: Metastatic renal cell carcinoma (mRCC) management guidelines recommend brain imaging if clinically indicated and the rate of occult central nervous system (CNS) metastasis is not well-defined. Early detection could have major therapeutic implications, because timely interventions may limit morbidity and mortality. Patients and Methods: A retrospective review was performed to characterize patients with mRCC incidentally diagnosed with asymptomatic brain metastases during screening for clinical trial participation at Gustave Roussy and Memorial Sloan Kettering Cancer Center. Descriptive statistics and time-to-event methods were used to evaluate the cohort. Results: Across 68 clinical trials conducted between 2001 and 2019 with a median 14.1-month follow-up, 72 of 1,689 patients (4.3%) with mRCC harbored occult brain metastases. The International Metastatic RCC Database Consortium (IMDC) risk status was favorable (26%), intermediate (61%), and poor (13%), and 86% of patients had ≥2 extracranial sites of disease, including lung metastases in 92% of patients. CNS involvement was multifocal in 38.5% of patients, and the largest brain metastasis was >1 cm in diameter in 40% of the cohort. Localized brain-directed therapy was pursued in 93% of patients, predominantly radiotherapy. Median overall survival was 10.3 months (range, 7.0–17.9 months), and the 1-year overall survival probability was 48% (95% CI, 37%–62%). IMDC risk and number or size of lesions did not correlate with survival (log-rank, P=.3, P=.25, and P=.067, respectively). Conclusions: This large multi-institutional mRCC cohort study identified occult brain metastasis in a notable proportion of patients (4.3%) and highlights that the risk of asymptomatic CNS involvement extends to those with favorable risk features per IMDC risk assessment. These data provide rationale for brain screening in patients with advanced RCC.