An Annual Symposium on Disparities in Milwaukee, WI, with a 2023 Focus on Older Adults with Cancer.

PURPOSE OF REVIEW: Cancer-related inequities are prevalent in Wisconsin, with lower survival rates for breast, colorectal, and lung cancer patients from marginalized communities. This manuscript describes the ongoing efforts at the Medical College of Wisconsin and potential pathways of community engagement to promote education and awareness in reducing inequities in cancer care. RECENT FINDINGS: While some cancer inequities are related to aggressive disease biology, health-related social risks may be addressed through community-academic partnerships via an open dialogue between the community members and academic faculty. To develop potential pathways of community-academic partnerships, an annual Cancer Disparities Symposium concept evolved as a pragmatic and sustainable model in an interactive learning environment. In this manuscript, we describe the programmatic development and execution of the annual Cancer Disparities Symposium, followed by highlights from this year's meeting focused on geriatric oncology as discussed by the speakers.

Double-blind, randomized, phase 2 trial of maintenance sunitinib versus placebo after response to chemotherapy in patients with advanced urothelial carcinoma.

BACKGROUND: Angiogenesis contributes to the progression of urothelial carcinoma (UC). In the current study, the authors investigated the role of maintenance sunitinib in patients with advanced UC. METHODS: Patients with locally recurrent/metastatic UC and adequate organ function who achieved stable disease or a partial or complete response after 4 to 6 chemotherapy cycles were randomized to sunitinib at a dose of 50 mg/day (28 days on and 14 days off) or placebo. The primary endpoint was the 6-month progression rate. Secondary endpoints were safety, survival, change in serum vascular endothelial growth factor (VEGF)/soluble VEGF receptor-2 (sVEGFR2), and the activity of sunitinib in patients who developed disease progression while receiving placebo. A total of 38 eligible patients per treatment arm were required to select better therapy with 90% probability (α = .05). RESULTS: A total of 54 eligible patients were randomized to either the sunitinib arm (26 patients) or the placebo arm (28 patients). The median number of cycles received was 2 cycles per treatment arm. The most common grade 3 to 4 adverse events (graded according to version 3.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events) among patients receiving sunitinib were thrombocytopenia, diarrhea, mucositis, fatigue, and hypertension. There were no grade 3 or 4 adverse events noted among > 5% of patients receiving placebo. The 6-month progression rate was 72% versus 64%. The median progression-free survival (PFS) was 2.9 months (range, 0.5 months-32.5 months) versus 2.7 months (range, 0.8 months -65 months) for the sunitinib versus placebo arms, respectively. Patients receiving placebo were found to have no changes in their serum VEGF/sVEGFR2 levels over time. Patients treated with sunitinib had no significant change in their VEGF level, but the sVEGFR2 level significantly decreased after cycles 1 and 2 (P < .0001) and at the time of disease progression (P = .0002). A baseline VEGF level that was at or greater than the median was found to be correlated with a longer PFS. Sixteen patients who were receiving placebo received sunitinib at the time of disease progression, with the best responses being 1 partial response (6.3%), 6 cases of stable disease (37.5%), and 5 cases of progressive disease (31.3%); 4 patients were not evaluable for response. The median PFS was 3.7 months (range, 0.1 months-22 months). CONCLUSIONS: The current multicenter study was limited by premature closure and a small sample size. Maintenance sunitinib did not appear to improve the 6-month progression rate. Open-label sunitinib was found to have only modest activity. The sVEGFR2 level decreased among patients receiving sunitinib.

Long-Term Outcomes of Dose-Escalated Pelvic Lymph Node Intensity-Modulated Radiation Therapy (IMRT) With a Simultaneous Hypofractionated Boost to the Prostate for Very High-Risk Adenocarcinoma of the Prostate: A Prospective Phase II Clinical Trial.

PURPOSE: There remains limited data as to the feasibility, safety, and efficacy of higher doses of elective radiation therapy to the pelvic lymph nodes in men with high-risk prostate cancer. We conducted a phase II study to evaluate moderate dose escalation to the pelvic lymph nodes using a simultaneous integrated boost to the prostate. METHODS AND MATERIALS: Patients were eligible with biopsy-proven adenocarcinoma of the prostate, a calculated lymph node risk of at least 25%, Karnofsky performance scale ≥70, and no evidence of M1 disease. Acute and late toxicity were prospectively collected at each follow-up using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). The pelvic lymph nodes were treated to a dose of 56 Gy over 28 fractions with a simultaneous integrated boost to the prostate to a total dose of 70 Gy over 28 fractions using intensity-modulated radiation therapy. RESULTS: Thirty patients were prospectively enrolled from October 2010 to August 2014. Median patient age was 70 years (57-83), pretreatment prostate-specific antigen was 11.5 ng/mL (3.23-111.5), T stage was T2c (T1c-T3b), and Gleason score was 9 (6-9). CTCAE v4.0 rate of any grade 1 or 2 genitourinary and gastrointestinal toxicity were 55% and 44%, respectively, and there was 1 reported acute grade 3 genitourinary and gastrointestinal toxicity, both unrelated to protocol therapy. With a median follow-up of 6.4 years, the biochemical failure free survival rate was 80.2%, and mean biochemical progression free survival was 8.3 years (95% confidence interval [CI], 7.2-9.4). The prostate cancer specific survival was 95.2%, and mean prostate cancer specific survival was 8.7 years (95% CI, 8.0-9.4). Five-year distant metastases free survival was 96%. Medians were not reached. CONCLUSIONS: In this single arm, small, prospective feasibility study, nodal radiation therapy dose escalation was safe, feasible, and seemingly well tolerated. Rates of progression free survival are highly encouraging in this population of predominately National Comprehensive Cancer Network very high-risk patients.

The Role of Metastasectomy in Urothelial Carcinoma: Where Are We in 2020?

Systemic therapy is the mainstay of treatment for metastatic urothelial carcinoma (UC). Responses to first-line platinum-based therapy tend to be short-lived with potential toxicity. Despite the approval of checkpoint inhibitors, the long-term prognosis for patients with metastatic UC remains dismal. Herein we report the case of a patient with a solitary pulmonary metastatic lesion of urothelial origin as the only site of metastatic disease who remained free of disease for more than 2 years without systemic therapy after metastasectomy. We review the literature discussing the role of combined surgical and medical management of oligometastatic UC. As our case illustrates, a growing body of evidence suggests a potential role for a multimodal approach in patients with oligometastatic UC.

Phase II trial of carboplatin and paclitaxel in papillary renal cell carcinoma.

BACKGROUND: Cytotoxic chemotherapy has not been well investigated in non-clear-cell renal cell carcinoma (RCC). A phase II study was thus conducted to assess the efficacy of carboplatin and paclitaxel in such patients. PATIENTS AND METHODS: Patients were treated with carboplatin (area under the curve of 6) and paclitaxel 225 mg/m2 every 21 days and assessed for measurable disease response every 2 cycles. An initial 20 patients were planned to be enrolled to rule out a null hypothesized 15% response rate. RESULTS: Seventeen patients were enrolled, of which 16 patients had papillary and 1 had collecting duct histology. The patient with collecting duct histology had a complete response, but no responses were observed in patients with papillary histology and the trial was thus terminated early. Toxicities were as expected for the carboplatin and paclitaxel regimen. CONCLUSION: Carboplatin and paclitaxel is not an active regimen in patients with metastatic papillary RCC. Future studies should explore the role of this or similar regimens in collecting duct carcinoma.

Treatment of older patients with high-risk myelodysplastic syndromes (MDS): the emerging role of allogeneic hematopoietic stem cell transplantation (Allo HSCT).

MDS are myeloid clonal hematologic disorders that are most commonly diagnosed in the seventh decade of life. Several treatment options are currently available. However, allo HSCT remains the only curative therapy. Unfortunately, despite the higher incidence of MDS in the older population, less than 10 % of patients undergoing allo HSCT for MDS are > 65 years old. In this paper we discuss the various treatment options in older patients with high-risk MDS with particular emphasis on the role of allo HSCT in older MDS patients.

Obese frailty, physical performance deficits, and falls in older men with biochemical recurrence of prostate cancer on androgen deprivation therapy: a case-control study.

OBJECTIVES: To test the hypothesis that early androgen deprivation therapy (ADT) has no proven survival advantage in older men with biochemical recurrence (BCR) of prostate cancer (PCa), and it may contribute to geriatric frailty. METHODS: We conducted a case-control study of men aged 60+ years with BCR on ADT (n = 63) vs PCa survivors without recurrence (n = 71). Frailty prevalence, "obese" frailty, Short Physical Performance Battery (SPPB) scores, and falls were compared. An exploratory analysis of frailty biomarkers (C-reactive protein, erythrocyte sedimentation rate, hemoglobin, albumin, and total cholesterol) was performed. Summary statistics and univariate and multivariate regression analyses were conducted. RESULTS: More patients on ADT were obese (body mass index >30; 46.2% vs 20.6%; P = .03). There were no statistical differences in SPPB (P = .41) or frailty (P = .20). Using a proposed "obese" frailty criteria, 8.7% in ADT group were frail and 56.5% were "prefrail," compared with 2.9% and 48.8% of controls (P = .02). Falls in the last year were higher in the ADT group (14.3% vs 2.8%; P = .02). In analyses controlling for age, clinical characteristics, and comorbidities, the ADT group trended toward significance for "obese" frailty (P = .14) and falls (OR = 4.74, P = .11). Comorbidity significantly increased the likelihood of "obese" frailty (P = .01) and falls (OR 2.02, P = .01). CONCLUSIONS: Men with BCR on ADT are frailer using proposed modified "obese" frailty criteria. They may have lower performance status and more falls. A larger, prospective trial is necessary to establish a causal link between ADT use and progression of frailty and disability.

WITHDRAWN: Cognitive effects of androgen deprivation therapy in an older cohort of men with prostrate cancer.

This article has been withdrawn from Critical Reviews in Oncology/Hematology. With the permission of the authors, it has been published in Volume1, issue 1 of the Journal of Geriatric Oncology (www.geriatriconcology.net). The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Cognitive effects of androgen deprivation therapy in an older cohort of men with prostate cancer.

OBJECTIVE: To determine the baseline prevalence of cognitive impairment in older men treated with ADT and to assess changes in cognitive performance over time. METHODS AND RESULTS: Thirty-two patients (median age of 71 years, range 51-87) were administrated an extensive neuropsychological testing battery prior to ADT initiation, with 21 (65%) completing post-treatment evaluations 6 months later. At baseline, 45% scored >1.5 standard deviations below the mean on > or = 2 neuropsychological measures. Using standardized inferential statistics, no change in cognition was documented following treatment. The Reliable Change Index revealed that, on a case-by-case basis, 38% demonstrated a decline in measures of executive functioning and 48% showed improvement on measures of visuospatial abilities. Within exploratory analyses, patients who scored below expectation at baseline displayed no change in cognition, while patients with average or better scores at baseline displayed improvements in visuospatial planning and timed tests of phonemic fluency. CONCLUSIONS: We found a high prevalence of lower than expected cognitive performance among a sample of patients just starting ADT for prostate cancer. Assessment of baseline cognitive function should be taken into account for future research and to inform clinical management.

Management of complications of androgen deprivation therapy in the older man.

Prostate cancer is the most common malignancy in older men. With the aging of the population, the number of older men with prostate cancer will grow rapidly. Androgen deprivation therapy (ADT) is the mainstay of treatment for men with systemic disease and is increasingly utilized as primary therapy or in combination with other therapies for localized disease. Side effects of therapy are multifold and include hot flashes, osteoporosis, and adverse psychological and metabolic effects. Recent research has illustrated that ADT can negatively impact the functional, cognitive, and physical performance of older men. Patients with prostate cancer, despite recurrence of the disease, have a long life expectancy and may be subjected to the side effects of ADT for many years. This review highlights the complications of ADT and approaches to management. We also provide recommendations for assessment and management of ADT complications among the most vulnerable and frail older male patients.

Patient anxiety about prostate cancer independently predicts early initiation of androgen deprivation therapy for biochemical cancer recurrence in older men: a prospective cohort study.

PURPOSE: Androgen deprivation therapy (ADT) is first-line therapy for patients with prostate cancer (PCA) who experience biochemical recurrence (BCR). However, the optimal timing of ADT initiation is uncertain, and earlier ADT initiation can cause toxicities that lower quality of life (QOL). We tested the hypothesis that elevated cancer anxiety leads to earlier ADT initiation for BCR in older men. PATIENTS AND METHODS: We conducted a prospective cohort study of older patients with BCR of PCA (n = 67). Patients completed questionnaires at presentation and each follow-up visit until initiation of ADT. PCA-specific anxiety was measured with the Memorial Anxiety Scale for Prostate Cancer (MAX-PC). Other collected data included demographics, clinical information, and general anxiety information. Treating oncologists were surveyed about their recommendations for ADT initiation. The primary outcome was the time to ADT initiation. Univariate, multivariate logistic regression, and time-to-event analyses were conducted to evaluate whether cancer anxiety was a predictor of earlier initiation of ADT. RESULTS: Thirty-three percent of patients initiated ADT at the first or second clinic visit. Elevated PCA anxiety (MAX-PC > 16) was the most robust predictor in multivariate analyses of early initiation (odds ratio [OR], 9.19; P = .01). PSA also independently correlated with early initiation (OR, 1.31; P = .01). PSA did not correlate with MAX-PC. CONCLUSION: Cancer anxiety independently and robustly predicts earlier ADT initiation in older men with BCR. For older patients with PCA, earlier ADT initiation may not change life expectancy and can negatively impact QOL. PCA-specific anxiety is a potential target for a decision-making intervention in this setting.

Falls and physical performance deficits in older patients with prostate cancer undergoing androgen deprivation therapy.

OBJECTIVES: Men experience a decrease in lean muscle mass and strength during the first year of androgen deprivation therapy (ADT). The prevalence of falls and physical and functional impairment in this population have not been well described. METHODS: A total of 50 men aged 70 years and older (median 78) receiving ADT for systemic prostate cancer (80% biochemical recurrence) underwent functional and physical assessments. The functional assessments included Katz's Activities of Daily Living (ADLs) and Lawton's Instrumental Activities of Daily Living (IADLs). Patients completed the Vulnerable Elder's Survey-13, a short screening tool of self-perceived functional and physical performance ability. Physical performance was assessed using the Short Physical Performance Battery. The history of falls was recorded. Of the 50 patients, 40 underwent follow-up assessment with the same instruments 3 months after the initial assessment. RESULTS: Of the 50 men, 24% had impairment in the ADLs, 42% had impairment in the IADLs, 56% had abnormal Short Physical Performance Battery findings, and 22% reported falls within the previous 3 months. Within the Short Physical Performance Battery, deficits occurred within all subcomponents (balance, walking, and chair stands). On univariate analysis, age, deficits in ADLs and IADLs, and abnormal cognitive and functional screen findings were associated with an increased risk of abnormal physical performance. ADL deficits, the use of an assistive device, and abnormal functional screen findings were associated with an increased risk of falling. CONCLUSIONS: The results of our study have shown that older men with prostate cancer receiving long-term ADT exhibit significant functional and physical impairment and are at risk of falls that is greater than that for similar-aged cohorts. Careful assessment of the functional and physical deficits in older patients receiving ADT is warranted.

Does androgen-deprivation therapy accelerate the development of frailty in older men with prostate cancer?: a conceptual review.

The majority of men with prostate cancer are aged > or =65 years. Men, as they age, are more likely to suffer from impaired physical function. The standard treatment for recurrent prostate cancer is androgen-deprivation therapy (ADT). Well-established toxicities from ADT include lean weight loss or sarcopenia, muscle weakness, fatigue, and reduced activity levels. Frailty is a term from geriatrics that describes older individuals with limited physiologic reserve who are at significant risk for adverse outcomes, including falls, disability, hospitalization, and death. An increasingly accepted definition of frailty is a syndrome in which > or =3 of the following are present: unintentional (lean) weight loss > or =10 pounds in the past year, weakness (measured by grip strength), slow walking speed, self-reported exhaustion, and low physical activity. This clinical syndrome overlaps closely with the known toxicities of ADT. In addition, alterations in the inflammatory system, neuroendocrine system, and energy production are associated with this syndrome, as evidenced by biomarkers such as C-reactive protein, interleukin-6, and tumor necrosis factor-alpha. For this article, the authors reviewed the evidence for the effect of ADT on each of the 5 frailty components plus the identified biomarkers, and the evidence indicates that ADT may accelerate the development of frailty in vulnerable older men with prostate cancer. Given the association of frailty with important clinical outcomes such as hospitalization and death, this potential consequence of ADT should be considered carefully when initiating therapy in older patients with recurrent prostate cancer.

Suppression of bone density loss and bone turnover in patients with hormone-sensitive prostate cancer and receiving zoledronic acid.

OBJECTIVE: To report a randomized, placebo-controlled study of treatment with zoledronic acid every 3 months in patients with hormone-sensitive prostate cancer, both with and without bone metastases, to assess the effect on bone mineral density (BMD) and markers of bone turnover. PATIENTS AND METHODS: Eligible patients included those with prostate cancer and on androgen-deprivation therapy for <12 months. Patients received zoledronic acid 4 mg intravenously, or placebo, every 3 months for four treatments. BMD, urinary N-telopeptides of type I collagen (NTX), and serum bone alkaline phosphatase (BAP) were measured every 3 months. In all, 42 patients were randomized. RESULTS: After excluding BMD data from sites of known metastases, patients receiving zoledronic acid had a relative increase in BMD compared with those receiving placebo, of 4.2% and 7.1% at the femoral neck and lumbar spine, respectively. NTX and BAP decreased significantly in patients receiving zoledronic acid. NTX and BAP levels were significantly higher at baseline in patients with bone metastases than in those without. CONCLUSIONS: Treatment with zoledronic acid every 3 months preserved bone density and suppressed markers of bone turnover in patients with androgen-deprived prostate cancer, both with and without bone metastases.

A pilot study of the vulnerable elders survey-13 compared with the comprehensive geriatric assessment for identifying disability in older patients with prostate cancer who receive androgen ablation.

BACKGROUND: Impairments in geriatric domains adversely affect health outcomes of the elderly. The Comprehensive Geriatric Assessment (CGA) is a key component of the treatment approach for older cancer patients, but it is time consuming. In this pilot study, the authors evaluated the validity of a brief, functionally based screening tool, the Vulnerable Elders Survey-13 (VES-13), for identifying older patients with prostate cancer (PCa) with impairment in the oncology clinic setting. METHODS: Patients with PCa aged >or=70 years who actively were receiving androgen ablation treatment and who were followed within the clinics at the University of Chicago were eligible. Patients self-completed the VES-13 and CGA instruments and repeated the VES-13 1 month later. Physical performance and cognitive assessments were administered by a research assistant. RESULTS: Of 50 participating patients, 50% were identified as impaired by the VES-13 (score >or=3). Sixty percent of patients scored as impaired on >or=2 tests within the CGA, exhibiting deficits in multiple domains. The reliability of the VES-13 (Pearson correlation coefficient) was 0.92. The cut-off score of 3 on the VES-13 had 72.7% sensitivity and 85.7% specificity for CGA deficits and was highly predictive for identifying impairment (area under the receiver operating characteristic curve, 0.90). Patients who had mean VES-13 scores >or=3 performed significantly worse on evaluations of activities of daily living (P = .001), physical performance (P = .002), comorbidity (P = .004), and cognitive impairment (P = .003). CONCLUSIONS: Functional and cognitive impairments are highly prevalent among older patients with PCa who receive androgen ablation in oncology clinics. The current results indicated that the brief VES-13 performed nearly as well as a conventional CGA in detecting geriatric impairment in this population.