The most recent (eighth) edition of the American Joint Committee on Cancer (AJCC) staging system divides invasive cutaneous melanoma into two broad groups: \"low-risk\" (stage IA-IIA) and \"high-risk\" (stage IIB-IV). While surveillance imaging for high-risk melanoma patients makes intuitive sense, supporting data are limited in that they are mostly respective and used varying methods, schedules, and endpoints. As a result, there is a lack of uniformity across different dermatologic and oncologic organizations regarding recommendations for follow-up, especially regarding imaging. That said, the bulk of retrospective and prospective data support imaging follow-up for high-risk patients. Currently, it seems that either positron emission tomography (PET) or whole-body computerized tomography (CT) are reasonable options for follow-up, with brain magnetic resonance imaging (MRI) preferred for the detection of brain metastases in patients who can undergo it. The current era of effective systemic therapies (ESTs), which can improve disease-free survival (DFS) and overall survival (OS) beyond lead-time bias, has emphasized the role of imaging in detecting various patterns of EST response and treatment relapse, as well as the importance of radiologic tumor burden.

BACKGROUND: There is currently no standardised definition for patients at high risk of recurrence of human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (eBC; stages 1-3) after surgery. This modified Delphi panel aimed to establish expert UK consensus on this definition, separately considering hormone receptor (HR)-positive and triple-negative (TN) patients.
METHODS: Over three consecutive rounds, results were collected from 29, 24 and 22 UK senior breast cancer oncologists and surgeons, respectively. The first round aimed to determine key risk factors in each patient subgroup; subsequent rounds aimed to establish appropriate risk thresholds. Consensus was pre-defined as ≥70% of respondents.
RESULTS: Expert consensus was achieved on need to assess age, tumour size, tumour grade, number of positive lymph nodes, inflammatory breast cancer and risk prediction tools in all HER2-negative patients. There was additional agreement on use of tumour profiling tests and biomarkers in HR-positive patients, and pathologic complete response (pCR) status in TN patients. Thresholds for high recurrence risk were subsequently agreed. In HR-positive patients, these included age <35 years, tumour size >5 cm (as independent risk factors); tumour grade 3 (independently and combined with other high-risk factors); number of positive nodes ≥4 (independently) and ≥1 (combined). For TN patients, the following thresholds reached consensus, both independently and in combination with other factors: tumour size >2 cm, tumour grade 3, number of positive nodes ≥1.
CONCLUSIONS: The results may be a valuable reference point to guide recurrence risk assessment and decision-making after surgery in the HER2-negative eBC population.

In KEYNOTE-564, adjuvant pembrolizumab, a PD-1 antibody, significantly improved disease-free survival (DFS) in localised clear-cell renal cell carcinoma (ccRCC) with a high risk of relapse. In 2021, the European Association of Urology RCC Guidelines Panel issued a weak recommendation for adjuvant pembrolizumab for high-risk ccRCC as defined by the trial until final overall survival data and results from other trials were available. Meanwhile, the primary DFS endpoints were not met for adjuvant atezolizumab (PD-L1 inhibitor; IMmotion010), adjuvant nivolumab plus ipilimumab (CheckMate 914), or perioperative nivolumab (PROSPER). Owing to heterogeneity, a meta-analysis is not recommended. Pembrolizumab remains the only immune checkpoint inhibitor currently recommended in this setting. Overall survival data are immature and biomarkers to predict outcome are lacking. Uncertainty exists and overtreatment is occurring. Treatment decisions should be made with caution and with the involvement of each patient. PATIENT SUMMARY: New results from three trials of immunotherapy after surgery for kidney cancer to reduce the risk of recurrence showed no improvement with these treatments. These results are in contrast to an earlier study that showed that the antibody pembrolizumab did extend the time before kidney cancer recurrence, even though it is not yet clear if overall survival is longer. Thus, we cautiously recommend pembrolizumab as additional treatment in high-risk kidney cancer after surgery, but patient preference should be carefully considered and the risk of overtreatment should be discussed.

To explore rates of under- and overscreening for cervical cancer among a national cohort.
The MarketScan database, a national administrative database of employee-sponsored insurance, was queried for elements relevant to cervical cancer screening among women aged 21-65 with 6 years of continuous enrollment (2015-2019). Average-risk women were defined as those without high-risk medical conditions or abnormal screening histories, and without evidence of hysterectomy with removal of the cervix for benign indications. Average-risk women were considered adequately screened if they had Pap tests alone at 2.5-3.5 year intervals, or HPV tests or co-tests at 4.5-5.5 year intervals. Logistic regressions were used to predict the odds of receiving guideline-adherent screening, underscreening, and overscreening.
Among 1,872,809 eligible patients, 1,471,063 (78.5%) qualified for routine screening. Of these, only 18.1% received guideline-adherent screening, and 25.4% were unscreened during the 6-year period. Younger women (aged 21-39) were more likely to be overscreened [OR 1.46]. Older women (aged 50-64) were more likely to be underscreened or unscreened during the study period [OR 2.54]. Guideline-adherent screening was highest with HPV testing alone (80%) followed by co-testing (44%), and lowest with cytology alone (15%). A total of 329,062 women in this general population sample (18%) met high-risk criteria that required increased frequency of screening.
High rates of both underscreening and overscreening indicate a need for additional strategies to improve guideline-adherent care.
N/A.

Adjuvant treatment of nonmetastatic high-risk renal cell carcinoma is an unmet medical need. In the past, several tyrosine kinase inhibitor trials have failed to demonstrate an improvement of disease-free survival (DFS) in this setting. Only one trial (S-TRAC) provided evidence for improved DFS with sunitinib but without an overall survival (OS) signal. Keynote-564 is the first trial of an immune checkpoint inhibitor that significantly improved DFS with adjuvant pembrolizumab, a programmed death receptor-1 antibody, in clear cell renal cell carcinoma with a high risk of relapse. The intention-to-treat population, which included a group of patients after metastasectomy and no evidence of disease (M1 NED), had a significant DFS benefit. The OS data are not mature as yet. The Renal Cell Carcinoma Guideline Panel issues a weak recommendation for the adjuvant use of pembrolizumab for high-risk clear cell renal carcinoma, as defined by the trial until final OS data are available. However, the trial reilluminates the discussion on when and in whom metastasectomy should be performed. Here, caution is necessary not to perform metastasectomy in patients with poor prognostic features and rapid progressive disease, which must be excluded by a confirmatory scan of disease status prior to planned metastasectomy. PATIENT SUMMARY: New data from the adjuvant immune checkpoint inhibitor trial with pembrolizumab (a programmed death receptor-1 antibody) for the treatment of high-risk clear cell renal cell carcinoma (ccRCC) after surgery showed that the drug prolonged the period of being cancer free significantly, although whether it prolonged survival remained uncertain. Consequently, pembrolizumab is cautiously recommended as additional (ie, adjuvant) treatment in high-risk ccRCC after kidney cancer surgery.

An increasing number of maternity care providers encounter pregnant women who request less care than recommended. A designated outpatient clinic for women who request less care than recommended was set up in Nijmegen, the Netherlands. The clinic\'s aim is to ensure that women make well-informed choices and arrive at a care plan that is acceptable to all parties. The aim of this study is to make the clinic\'s approach explicit by examining care providers\' experiences who work with or within the clinic.
qualitative analysis of in-depth interviews with Dutch midwives (n = 6) and obstetricians (n = 4) on their experiences with the outpatient clinic \"Maternity Care Outside the Guidelines\" in Nijmegen, the Netherlands.
Four main themes were identified: (1) \"Trusting mothers, childbirth and colleagues\"; (2) \"A supportive communication style\"; (3) \"Continuity of carer\"; (4) \"Willingness to reconsider responsibility and risk\". One overarching theme emerged from the data, which was \"Guaranteeing women\'s autonomy\". Mutual trust is a prerequisite for a constructive dialogue about birth plans and can be built and maintained more easily when there is continuity of carer during pregnancy and birth. Discussing birth plans at the clinic was believed to be successful because the care providers listen to women, take them seriously, show empathy and respect their right to refuse care. A change in vision on responsibility and risk is needed to overcome barriers such as providers\' fear of adverse outcomes. Taking a more flexible approach towards care outside the guidelines demands courage but is necessary to guarantee women\'s autonomy.
In order to fulfil women\'s needs and to prevent negative choices, care providers should care for women with trust, respect for autonomy, and provide freedom of choice and continuity. Care providers should reflect on and discuss why they are reluctant to support women\'s wishes that go against their personal values. The structured approach used at this clinic could be helpful to maternity care providers in other contexts, to make them feel less vulnerable when working outside the guidelines.

The National Osteoporosis Guideline Group (NOGG) has developed intervention thresholds based on FRAX® to characterise patients at high and very high risk of fracture.
BACKGROUND: Guidelines for the assessment of fracture risk have begun to categorise patients eligible for treatment into high and very high risk of fracture to inform choice of therapeutic approach. The aim of the present study was to develop intervention thresholds based on the hybrid assessment model of NOGG.
METHODS: We examined the impact of intervention thresholds in a simulated cross-sectional cohort of women age 50 years or more from the UK with the distribution of baseline characteristics based on that in the FRAX cohorts. The prevalence of very high risk using the hybrid model was compared with age-dependent thresholds used by the International Osteoporosis Foundation and the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (IOF/ESCEO). The appropriateness of thresholds was tested based on the populations treated with anabolic agents.
RESULTS: With an upper intervention threshold using the IOF/ESCEO criteria, 56% of women age 50 years or more would be characterised at very high risk. This compares with 36% using the IOF/ESCEO criteria and an age-specific intervention threshold over all ages. With an upper intervention threshold of 1.6 times the pre-existing intervention threshold, 10% of women age 50 years or more would be characterised at very high risk. The data from phase 3 studies indicate that most trial participants exposed to romosozumab or teriparatide would fall into the very high-risk category.
CONCLUSIONS: Proposals for FRAX-based criteria for very high risk for the NOGG hybrid model categorise a small proportion of women age 50 years or more (10%) in this highest risk stratum. The level of risk identified was comparable to that of women enrolled in trials of anabolic agents.

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The purpose of this article is to overview the existing breast cancer screening guidelines for women at high risk from world-leading specialty societies. Accumulation of evidence and development of accessible genetic testing strategies have changed the idea of breast cancer screening for high-risk women. Personalized tailor-made screening adjusted for risk factors has been conducted in accordance with guidelines. The use of imaging modalities other than mammography including contrast-enhanced MRI and other various strategies for improving screening are discussed. The present review also mentions the existing challenges in high-risk screening and the latest information based on two large-scale studies.

Background: The incidence of micropapillary thyroid carcinoma (mPTC) has increased in the last decade. Active surveillance (AS) has been proposed as an alternative management for low-risk mPTC based on preoperative Kuma criteria. Controversy still exists on how to appropriately manage this group of patients, as some low-risk mPTC may harbor some postoperative features associated with disease recurrence as described in the 2015 American Thyroid Association (ATA) guidelines. Methods: We retrospectively reviewed 108 patients with histopathologic diagnosis of mPTC after surgery at a third level hospital in Mexico City from 2000 to 2018. Demographic and clinicopathologic data were analyzed as predictors for disease recurrence and/or metastatic disease (lymph node or distant). Comparison between group stratification based on preoperative Kuma criteria and postoperative 2015 ATA guidelines risk criteria for disease recurrence was performed. Measures of diagnostic accuracy were obtained for preoperative risk features according to the Kuma criteria. Results: Of 108 patients, 79 (73%) were classified as preoperative high-risk mPTC and 29 (27%) as low risk based on the Kuma criteria. Of these 79 high-risk patients, 38 (48%) were reclassified as low risk for disease recurrence, 12 (15%) as intermediate risk, and 29 (37%) remained as high risk based on the 2015 ATA risk criteria. Of the 29 preoperative low-risk patients, 19 (65.5%) remained as postoperative low risk for disease recurrence, 2 (7%) as intermediate risk, and 8 (27.5%) as high risk. Higher accuracy of preoperative risk features was obtained for lymph node and distant metastases, 84.2% and 97.2%, respectively. After multivariate analysis, age <40 years and microscopic extrathyroidal extension (ETE) were associated with higher risk for metastatic disease (lymph node or distant) in our cohort. Conclusions: Patients with mPTC under 40 years old and microscopic ETE are more prone to develop metastatic disease (lymph node or distant). One-third of our patients stratified as low-risk mPTC according to the Kuma criteria for AS had histopathologic features associated with a more aggressive clinical behavior or structural recurrence. In addition, lymph node and distant metastases are the preoperative risk features with the highest diagnostic accuracy for preoperative risk stratification.