In sub-Saharan Africa (SSA), urgent action is needed to curb a growing crisis in cancer incidence and mortality. Without rapid interventions, data estimates show a major increase in cancer mortality ...from 520 348 in 2020 to about 1 million deaths per year by 2030. Here, we detail the state of cancer in SSA, recommend key actions on the basis of analysis, and highlight case studies and successful models that can be emulated, adapted, or improved across the region to reduce the growing cancer crises. Recommended actions begin with the need to develop or update national cancer control plans in each country. Plans must include childhood cancer plans, managing comorbidities such as HIV and malnutrition, a reliable and predictable supply of medication, and the provision of psychosocial, supportive, and palliative care. Plans should also engage traditional, complementary, and alternative medical practices employed by more than 80% of SSA populations and pathways to reduce missed diagnoses and late referrals. More substantial investment is needed in developing cancer registries and cancer diagnostics for core cancer tests. We show that investments in, and increased adoption of, some approaches used during the COVID-19 pandemic, such as hypofractionated radiotherapy and telehealth, can substantially increase access to cancer care in Africa, accelerate cancer prevention and control efforts, increase survival, and save billions of US dollars over the next decade. The involvement of African First Ladies in cancer prevention efforts represents one practical approach that should be amplified across SSA. Moreover, investments in workforce training are crucial to prevent millions of avoidable deaths by 2030. We present a framework that can be used to strategically plan cancer research enhancement in SSA, with investments in research that can produce a return on investment and help drive policy and effective collaborations. Expansion of universal health coverage to incorporate cancer into essential benefits packages is also vital. Implementation of the recommended actions in this Commission will be crucial for reducing the growing cancer crises in SSA and achieving political commitments to the UN Sustainable Development Goals to reduce premature mortality from non-communicable diseases by a third by 2030.
The causes of cancer health inequities are complex, multilevel, and intersectional. The typical disciplines and data used to address these inequities focus on public health, health services, ...clinical, and fundamental science. Fundamental causes such as systemic racism are a source of much health inequity, but a broader scope of fundamental causes may be considered. Geohistorical events may intersect with other fundamental causes of health inequities. In this study, an example of relationships between ancient geological events, slavery, and subsequent effects of systematic racism are identified. These relationships support the hypothesis that health inequities have deep and complex origins. Geohistorical factors precede social, economic, and political influences on health inequities, and suggest that a full understanding of cancer health inequities and their elimination may be informed by geohistorical events. Thus, addressing inequities may involve disciplines not typically involved in health equity collaborations, including geography, history, economics, political science, and others.
Germline testing (GT) is a central feature of prostate cancer (PCA) treatment, management, and hereditary cancer assessment. Critical needs include optimized multigene testing strategies that ...incorporate evolving genetic data, consistency in GT indications and management, and alternate genetic evaluation models that address the rising demand for genetic services.
A multidisciplinary consensus conference that included experts, stakeholders, and national organization leaders was convened in response to current practice challenges and to develop a genetic implementation framework. Evidence review informed questions using the modified Delphi model. The final framework included criteria with strong (> 75%) agreement (Recommend) or moderate (50% to 74%) agreement (Consider).
Large germline panels and somatic testing were recommended for metastatic PCA. Reflex testing-initial testing of priority genes followed by expanded testing-was suggested for multiple scenarios. Metastatic disease or family history suggestive of hereditary PCA was recommended for GT. Additional family history and pathologic criteria garnered moderate consensus. Priority genes to test for metastatic disease treatment included
and mismatch repair genes, with broader testing, such as
, for clinical trial eligibility.
was recommended for active surveillance discussions. Screening starting at age 40 years or 10 years before the youngest PCA diagnosis in a family was recommended for
carriers, with consideration in
, and mismatch repair carriers. Collaborative (point-of-care) evaluation models between health care and genetic providers was endorsed to address the genetic counseling shortage. The genetic evaluation framework included optimal pretest informed consent, post-test discussion, cascade testing, and technology-based approaches.
This multidisciplinary, consensus-driven PCA genetic implementation framework provides novel guidance to clinicians and patients tailored to the precision era. Multiple research, education, and policy needs remain of importance.
Abstract
The cancer disparities between people with incarceration histories compared with those who do not have those histories are vast. Opportunities for bolstering cancer equity among those ...impacted by mass incarceration exist in criminal legal system policy; carceral, community, and public health linkages; better cancer prevention, screening, and treatment services in carceral settings; expansion of health insurance; education of professionals; and use of carceral sites for health promotion and transition to community care. Clinicians, researchers, persons with a history of incarceration, carceral administrators, policy makers, and community advocates could play a cancer equity role in each of these areas. Raising awareness and setting a cancer equity plan of action are critical to reducing cancer disparities among those affected by mass incarceration.
Purpose
Prostate cancer mortality is predicted to nearly double by 2040 in Sub-Saharan Africa (SSA). The lack of prostate cancer screening in SSA contributes to late-stage diagnosis, treatment ...delays, and poor survival among patients. We analyzed the availability and use of prostate cancer screening, diagnostic and treatment guidelines, procedures, and costs in few SSA countries to determine factors for consideration in the development of prostate cancer screening guidelines for SSA.
Methods
We applied mixed methods approaches to collect data through an electronic survey administered to clinicians (oncologists, urologists, pathologists, nurses, and radiation oncologists) providing prostate cancer screening, diagnosis, and treatment services in multiple sub-Saharan countries.
Results
Inconsistencies in respondents’ understanding of the availability and use of prostate cancer screening guidelines in their countries were noted. Prostate Specific Antigen (PSA) and Digital Rectal Examination (DRE) were the most commonly available screening modalities. Available diagnostic procedures included a combination of prostate biopsies, transrectal ultrasonography, and DRE. Our study’s data suggest that PSA and DRE exams are available for early diagnosis and screening procedures. Availability of treatment modalities with curative intent and costs for prostate cancer related procedures varied between and within countries.
Conclusions
PSA and DRE are available for detecting prostate cancer and may detect aggressive cancers early, leading to improved outcomes. However, PSA screening is also associated with overdiagnosis and over-treatment. National prostate cancer policies should consider health systems, evidence-based guidelines, population characteristics and healthcare financing to ensure access to clinically relevant and safe prostate cancer related care.
Cancer results from complex interactions of multiple variables at the biologic, individual, and social levels. Compared to other levels, social effects that occur geospatially in neighborhoods are ...not as well-studied, and empiric methods to assess these effects are limited. We propose a novel Neighborhood-Wide Association Study(NWAS), analogous to genome-wide association studies(GWAS), that utilizes high-dimensional computing approaches from biology to comprehensively and empirically identify neighborhood factors associated with disease.
Pennsylvania Cancer Registry data were linked to U.S. Census data. In a successively more stringent multiphase approach, we evaluated the association between neighborhood (n = 14,663 census variables) and prostate cancer aggressiveness(PCA) with n = 6,416 aggressive (Stage≥3/Gleason grade≥7 cases) vs. n = 70,670 non-aggressive (Stage<3/Gleason grade<7) cases in White men. Analyses accounted for age, year of diagnosis, spatial correlation, and multiple-testing. We used generalized estimating equations in Phase 1 and Bayesian mixed effects models in Phase 2 to calculate odds ratios(OR) and confidence/credible intervals(CI). In Phase 3, principal components analysis grouped correlated variables.
We identified 17 new neighborhood variables associated with PCA. These variables represented income, housing, employment, immigration, access to care, and social support. The top hits or most significant variables related to transportation (OR = 1.05;CI = 1.001-1.09) and poverty (OR = 1.07;CI = 1.01-1.12).
This study introduces the application of high-dimensional, computational methods to large-scale, publically-available geospatial data. Although NWAS requires further testing, it is hypothesis-generating and addresses gaps in geospatial analysis related to empiric assessment. Further, NWAS could have broad implications for many diseases and future precision medicine studies focused on multilevel risk factors of disease.
Data on the efficacy of bilateral prophylactic mastectomy for breast cancer risk reduction in women with BRCA1 and BRCA2 (BRCA1/2) mutations are limited, despite the clinical use of this ...risk-management strategy. Thus, we estimated the degree of breast cancer risk reduction after surgery in women who carry these mutations.
Four hundred eighty-three women with disease-associated germline BRCA1/2 mutations were studied for the occurrence of breast cancer. Cases were mutation carriers who underwent bilateral prophylactic mastectomy and who were followed prospectively from the time of their center ascertainment and their surgery, with analyses performed for both follow-up periods. Controls were BRCA1/2 mutation carriers with no history of bilateral prophylactic mastectomy matched to cases on gene, center, and year of birth. Both cases and controls were excluded for previous or concurrent diagnosis of breast cancer. Analyses were adjusted for duration of endogenous ovarian hormone exposure, including age at bilateral prophylactic oophorectomy if applicable.
Breast cancer was diagnosed in two (1.9%) of 105 women who had bilateral prophylactic mastectomy and in 184 (48.7%) of 378 matched controls who did not have the procedure, with a mean follow-up of 6.4 years. Bilateral prophylactic mastectomy reduced the risk of breast cancer by approximately 95% in women with prior or concurrent bilateral prophylactic oophorectomy and by approximately 90% in women with intact ovaries.
Bilateral prophylactic mastectomy reduces the risk of breast cancer in women with BRCA1/2 mutations by approximately 90%.
Risk-reducing salpingo-oophorectomy (RRSO) has been widely adopted as a key component of breast and gynecologic cancer risk-reduction for women with BRCA1 and BRCA2 mutations. Despite 17% to 39% of ...all BRCA mutation carriers having a mutation in BRCA2, no prospective study to date has evaluated the efficacy of RRSO for the prevention of breast and BRCA-associated gynecologic (ovarian, fallopian tube or primary peritoneal) cancer when BRCA2 mutation carriers are analyzed separately from BRCA1 mutation carriers.
A total of 1,079 women 30 years of age and older with ovaries in situ and a deleterious BRCA1 or BRCA2 mutation were enrolled onto prospective follow-up studies at one of 11 centers from November 1, 1994 to December 1, 2004. Women self-selected RRSO or observation. Follow-up information through November 30, 2005, was collected by questionnaire and medical record review. The effect of RRSO on time to diagnosis of breast or BRCA-associated gynecologic cancer was analyzed using a Cox proportional-hazards model.
During 3-year follow-up, RRSO was associated with an 85% reduction in BRCA1-associated gynecologic cancer risk (hazard ratio HR = 0.15; 95% CI, 0.04 to 0.56) and a 72% reduction in BRCA2-associated breast cancer risk (HR = 0.28; 95% CI, 0.08 to 0.92). While protection against BRCA1-associated breast cancer (HR = 0.61; 95% CI, 0.30 to 1.22) and BRCA2-associated gynecologic cancer (HR = 0.00; 95% CI, not estimable) was suggested, neither effect reached statistical significance.
The protection conferred by RRSO against breast and gynecologic cancers may differ between carriers of BRCA1 and BRCA2 mutations. Further studies evaluating the efficacy of risk-reduction strategies in BRCA mutation carriers should stratify by the specific gene mutated.
More than 75% of cancer-related deaths occur from cancers for which we do not screen. New screening liquid biopsies may help fill these clinical gaps, although evidence of benefit still needs to be ...assessed. Which lessons can we learn from previous efforts to guide those of the future? Screening trials for ovarian, prostate, pancreatic, and esophageal cancers are revisited to assess the evidence, which has been limited by small effect sizes, short duration of early-stage disease relative to screening frequency, study design, and confounding factors. Randomized controlled trials (RCT) to show mortality reduction have required millions of screening-years, two-decade durations, and been susceptible to external confounding. Future RCTs with late-stage incidence as a surrogate endpoint could substantially reduce these challenges, and clinical studies demonstrating safety and effectiveness of screening in high-risk populations may enable extrapolation to broader average-risk populations. Multicancer early detection tests provide an opportunity to advance these practical study designs. Conditional approvals based on RCTs with surrogate endpoints, contingent upon real world evidence generation and continuation of trials to definitive endpoints, may lower practical barriers to innovation in cancer screening and enable greater progress.
To provide precise age-specific risk estimates of cancers other than female breast and ovarian cancers associated with pathogenic variants (PVs) in
and
for effective cancer risk management.
We used ...data from 3,184
and 2,157
families in the Consortium of Investigators of Modifiers of
to estimate age-specific relative (RR) and absolute risks for 22 first primary cancer types adjusting for family ascertainment.
PVs were associated with risks of male breast (RR = 4.30; 95% CI, 1.09 to 16.96), pancreatic (RR = 2.36; 95% CI, 1.51 to 3.68), and stomach (RR = 2.17; 95% CI, 1.25 to 3.77) cancers. Associations with colorectal and gallbladder cancers were also suggested.
PVs were associated with risks of male breast (RR = 44.0; 95% CI, 21.3 to 90.9), stomach (RR = 3.69; 95% CI, 2.40 to 5.67), pancreatic (RR = 3.34; 95% CI, 2.21 to 5.06), and prostate (RR = 2.22; 95% CI, 1.63 to 3.03) cancers. The stomach cancer RR was higher for females than males (6.89
2.76;
= .04). The absolute risks to age 80 years ranged from 0.4% for male breast cancer to approximately 2.5% for pancreatic cancer for
carriers and from approximately 2.5% for pancreatic cancer to 27% for prostate cancer for
carriers.
In addition to female breast and ovarian cancers,
and
PVs are associated with increased risks of male breast, pancreatic, stomach, and prostate (only
PVs) cancers, but not with the risks of other previously suggested cancers. The estimated age-specific risks will refine cancer risk management in men and women with
PVs.
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