Cancer Screening surgical oncology presentation

Checking for cancer (or for abnormal cells that may become cancer) in people who have no symptoms is called screening. Several screening tests have been shown to detect cancer early and to reduce the chance of dying from that cancer.

1. Cancer Screening Dr Venkateshen Palanisamy

2. What is screening? Definition : Cancer screening refers to performing a test or examination on an asymptomatic individual in pre clinical stage. The goal: C ancer screening is to prevent death and suffering from the disease in question through early therapeutic intervention

3. Requirements for cancer screening The disease burden is significant. The natural history of the disease is such that a detectable preclinical phase exists. A test or procedure must detect cancers earlier than if the cancers were detected as a result of the development of symptoms. Treatment initiated earlier as a consequence of screening results in an improved outcome. (These requirements are necessary but not sufficient for the test or procedure to be efficacious) (A screening test is efficacious when it leads to a decrease in cause-specific mortality)

4. Types - Screening Opportunistic vs programmatic Opportunistic – Doctor – Patient Programmatic – Mass screening Programmatic – always more effective

5. Performance Characteristics Of A Screening Test The degree to which a screening test can accurately discriminate between individuals with and without a particular disease is described by its performance characteristics Sensitivity Specificity Positive predictive value Negative predictive value Measure accuracy of test not the efficacy or effectiveness

6. Sensitivity vs specificity Inversely related EG : 1 - PSA as one lowers the threshold for considering a serum prostate-specific antigen (PSA) level to represent a positive screen, the sensitivity of the test increases and more cancers will be detected. This increased sensitivity comes at the cost of decreased specificity (i.e., more men without cancer will have positive screenings tests and therefore will be subjected to unnecessary diagnostic procedures). EG 2 : MAMMOGRAMS more subjective and operator dependent than others. For this reason, the sensitivity and specificity of screening mammography varies among radiologists.

7. Assessing screening test - biases Biases in screening – test make in appear efficacious when it is not Lead time bias Length bias Over diagnosis Selection bias

8. Lead time bias

9. Length bias

10. Over diagnosis Overdiagnosis is an extreme form of length bias and represents pure harm. It refers to the detection of tumors, often through highly sensitive modern imaging modalities and other diagnostic tests, that fulfill the histologic criteria for malignancy but are not biologically destined to harm the patient There are two categories of overdiagnosis: the detection of histologically defined cancers not destined to metastasize or harm the patient the detection of cancers not destined to metastasize or cause harm in the life span of the specific patient .

11. Neuroblastoma provides one of the most striking examples of overdiagnosis. 4 Urine vanillylmandelic acid (VMA) testing is a highly sensitive screening. After screening programs in Germany, Japan, and Canada showed marked increases in the incidence of this disease without a concomitant decline in mortality, it was noticed that nearby areas that did not screen had similar death rates with lower incidence.

12. Selection bias Selection bias occurs when enrollees in a clinical study differ from the general population. In fact people who voluntarily participate in clinical trials tend to be healthier than the general population, perhaps due to a greater interest in health and healthcare research. Screening studies tend to enroll individuals healthier than the general population. This so-called healthy volunteer effect can introduce a powerful bias if not adequately controlled for by randomization procedures

13. Assessing outcomes Goal : Reduce mortality from the disease in question (Disease specific mortality) Cohort studies Case control studies Randomized trials

14. Problems with trials Contamination Drop in Drop out Morbidity and mortality due to screening Invasive diagnostic and therapeutic procedures Anxiety Financial cost Risk benefit ratio not always determined Ethical issues

15. Screening guidelines Recomendations The Institute of Medicine (IOM) – Screening guidelines Recommendations The U.S. Preventive Services Task Force ( USPSTF) the American Cancer Society (ACS)

16. Breast cancer screening Initial methods C linical breast examinations (CBE) by a healthcare provider B reast self-examinations (BSE) Mammographies In recent years Ultrasound magnetic resonance imaging (MRI)

17. Self breast examination Two large studies In one, approximately 266,000 Chinese women were randomized to receive intensive BSE instruction with reinforcements and reminders compared to a control group receiving no instruction on BSE. At 10 years of follow-up, there was no difference in mortality, but the intervention arm had a significantly higher incidence of benign breast lesions diagnosed and breast biopsies preformed. In the second study, 124,000 Russian women were randomized to monthly BSEs versus no BSEs. There was no difference in mortality rates, despite the BSE group having a higher proportion of early stage tumors and a significant increase in the proportion of cancer patients surviving 15 years after diagnosis.

18. The health insurance plan study Results Started in 1963 61,000 women screened Three annual mammograms with breast examination vs no screening 30% less mortality rate at 10 years 18 years 25% reduction

19. Results Nine additional prospective randomized studies have been published. These studies provide the basis for the current consensus that screening women 40 to 75 years of age does reduce the relative risk of breast cancer death by 10% to 25%. The 10 studies demonstrate that the risk–benefit ratio is more favorable for women aged 60-69 > 50 – 59 > 40 – 49 years. Mammography has also been shown to be operator dependent, with better performance characteristics (higher sensitivity and specificity and lower FP rates) reported by high-volume centres

20. Screening below 50 years Less than 40 years low prevalence Younger women have a lower incidence of the disease, meaning they are less likely to have breast cancer compared to older women. A larger proportion have increased breast density, which can obscure lesions (lower sensitivity). Younger women are more likely to develop aggressive, fast-growing breast cancers that are diagnosed between regular screening visits. these interval cancers are not screen detected.

21. New modalities USG – Operator dependent High rate of false positive MRI – BRCA 1 , BRCA 2, Li Fraumeni syndrome, Cowden disease , strong family history More sensitive , Less specific High biopsy rate in young women

22. Newer modalities Full field digital mammography with Computer-aided detection Digital breast tomosynthesis

23. Molecular breast imaging - iv Tc 99 sestamibi and gamma camera Abbreviated (Fast) MRI – 3 to 5 mins

24. Harms of screening The harms and disadvantages of mammography screening include overdiagnosis, FP tests, FN tests, and the possibility of radiation induced breast cancer. Over diagnosis : greatest at first screening, varies with age, tumour type, grade of disease FP: 10% are called for additional testing and less than half will be diagnosed with beast cancer. FN: more common in young women and dense breast Certain histology types are difficult to see in mammogram- Mucinous and lobular tumours and rapidly growing tumours. Blend in with normal breast architecture.

25. Radiation A typical screening mammogram provides approximately 4 mSv of radiation . E stimated that annual mammographies will cause up to 1 case of breast cancer per 1,000 women screened from age 40 to age 80 years. Radiation exposure at younger ages causes a greater risk of breast cancer.

26. ACS recommendations: Women should have the opportunity to begin annual screening between the ages of 40 and 44 years. Women should undergo regular screening mammography starting at age 45 years. Women aged 45 to 54 years should be screened annually. Women aged 55 years and older should transition to biennial screening or have the opportunity to continue screening annually. Women should continue screening mammography as long as their overall health is good and they have a life expectancy of 10 years.

27. The ACS does not recommend CBE or BSE because of the paucity of data supporting them. The USPSTF, the American College of Physicians, and the Canadian Task Force on Periodic Health Examination recommend routine biennial screening beginning at age 50 years. For women aged 40 to 49 years, these groups advise physicians enter into a discussion with the patient.

28. GIT cancer screening – Colon cancer Screening with the rigid sigmoidoscope dates back to the late 1960s. The desire to examine the entire colon led to the use of barium enema and development of fecal occult blood tests (FOBTs). With the development of fiber optics, flexible sigmoidoscopy and later colonoscopy were employed. Today FOBT, stool DNA testing, flexible sigmoidoscopy, colonoscopy, and CT colonography and occasionally barium enema are all used in colorectal cancer screening. MRI colonoscopy is in development. Screening and endoscopic polypectomy reduces incidence by 20%

29. Types of test - Fecal occult blood test First test screening test Overall, 1% to 5% of FOBTs are positive, but only 2% to 10% of patients with positive tests have cancer. Land mark trial - The Minnesota Colon Cancer Control Study

30. The Minnesota Colon Cancer Control Study randomized 46,551 adults to one of three arms: annual FOBT, biennial screening, or usual care. A rehydrated guaiac test was used. With 13 years of follow-up , the annual screened arm had a 33% relative reduction in colorectal cancer mortality compared to the usual care group. At 18 years of follow-up , the biennially screened group had a 21% reduction in colorectal cancer mortality. This study would subsequently show that annual stool blood testing was associated with a 20% reduction in colon cancer incidence

31. Fecal immunochemical tests (FIT) FIT stool tests that react to human hemoglobin and do not react to hemoglobin in dietary products. They appear to have higher sensitivity and specificity for colorectal cancer when compared to nonrehydrated FOBT tests. FECAL DNA TESTING Fecal DNA testing is an emerging modality. These tests look for DNA sequences specific to colorectal polyps and colorectal cancer. They may have increased sensitivity and specificity compared to FOBT.

32. Flexible sigmoidoscopy NCI’s Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), a 21% reduction in colorectal cancer incidence a 26% reduction in colorectal cancer mortality W ith two sigmoidoscopies done 3 to 5 years apart compared with the usual care group after a median follow-up of 11.9 years.

33. Colonoscopy P referred screening method A positive FOBT, FIT, fecal DNA test, or sigmoidoscopy warrants a follow-up diagnostic colonoscopy. Perhaps, the best support for colonoscopy screening is indirect evidence from the Minnesota Colon Cancer Control Study , which required that all participants with a positive stool blood test have diagnostic imaging of the entire colon. In the Minnesota study, more than 40% of those screened annually eventually received a colonoscopy.

34. Virtual colonoscopy CT colonography or virtual colonoscopy allows a physician to visually reproduce the endoscopic examination on a computer screen. CT colonography involves the same preparation as a colonoscopy but is less invasive. The disadvantages of CT colonography include the fact that it does require a colonic prep and a finding on CT requires a follow-up diagnostic colonoscopy

35. Recommendations T he ACS now recommends average-risk adults begin screening at age 45 years Screening modalities should be chosen based on personal preference and access. 1. Annual high-sensitivity FOBT or FIT 2. Multitarget stool DNA testing every 3 years 3. Flexible sigmoidoscopy every 5 years 4. Colonoscopy every 10 years 5. Double-contrast barium enema every 5 years 6. CT colonography every 5 years

36. T he USPSTF guideline include 1. High sensitivity stool-based methods every year 2. FIT-DNA stool testing every 1 or 3 years 3. Colonoscopy every 10 years 4. CT colonography every 5 years 5. Flexible sigmoidoscopy every 5 years 6. Flexible sigmoidoscopy every 10 years plus FIT every year

37. Patients at High Risk for Colorectal Cancer

38. Other GI Malignancies Average risk – no screening guidelines High risk patients ESOPHAGUS – Barrets , chronic & severe GERD – endoscopy biopsy GASTRIC - atrophic gastritis or pernicious anemia, partial gastrectomy, history of sporadic adenomas, and FAP, HNPCC PANCREATIC CANCER – significant family h/O thin cut CT of abdomen – on going research for tumor markers LIVER - Screening for liver cancer or hepatocellular carcinoma (HCC) has focused on identifying very-high-risk individuals, such as those with cirrhosis or viral hepatitis , AFP – not significant

39. GYNECOLOGIC CANCER – Cervical Cancer Screening Dr. George Papanicolaou first introduced the Pap smear or Pap test in the early 1940s Adopted based on its ability to identify squamous premalignancies and malignancies (from the ectodermal cervix) and glandular dysplasia and adenocarcinoma (from the endocervix). The original Pap smear used an ectocervical spatula to apply a specimen (“smear”) to a glass slide. It later included an endocervical brush. The smear was fixed, stained, and manually examined under a microscope. That method is still used today but a liquid-based/thin-layer system capable of being analyzed by computer is gaining in popularity

40. HPV HPV - With increasing understanding of the role of human papillomavirus (HPV) in cervical disease Interest in developing tests to determine the presence of HPV DNA and RNA has grown. HPV-16 and HPV-18 are the cause of more than 70% of cervical cancers. 13 other HPV subtypes are known to be associated with cervical cancer. HPV screening can be used along with cytology (“ cotesting ”) In response to an abnormal cytologic test (“reflexive testing”) As a stand-alone test. One advantage of the liquid-based/thin-layer tests over the older smears is that they make reflexive testing easier to perform.

41. The utility of the HPV test is limited in younger women because a third or more of women in their 20s who have not received the HPV vaccine have active cervical HPV infections at any given time The overwhelming majority of these infections and resultant dysplasia will regress and resolve within an 8- to 24-month period. HPV infection in women older than 30 years is more likely to be persistent and clinically significant For women older than 30 years, screening for the presence of HPV DNA or RNA appears to be superior to cytology in identifying women at risk for cervical dysplasia and cancer HPV – Testing

42. Screening guidelines In 2017, the ACS issued guidelines Women younger than 21 years should not be screened regardless of their age of sexual initiation. Screening for cervical cancer should begin at 21 years of age. Women aged 21 to 29 years should receive cytology screening (with either conventional cervical cytology smears or liquid-based cytology) every 3 years. HPV testing should not be performed in this age group (although it can be used to follow up a diagnosis of ASC-US). For women aged 30 to 65 years, the preferred approach is to be screened every 5 years with both HPV testing and cytology (“ cotesting ”). It is also acceptable to continue screening every 3 years with cytology alone.

43. Women should discontinue screening after age 65 years if they have had three consecutive negative cytology tests or two consecutive negative HPV test results within the 10-year period before ceasing screening, with the most recent test occurring within the past 5 years. Women who have undergone a total hysterectomy for noncancerous conditions do not need to undergo cervical cancer screening. Women who have received HPV vaccinations should still be screened according to the mentioned schedule Women, regardless of age, should not be screened annually by any screening method

44. Screening in Low-Resource Countries Cytology and HPV testing are not widely available in much of the world. Cervical cancer is still a leading cause of death in many of these areas. Visual inspection of the cervix is a low-tech method of screening that is now recognized as having the potential to save thousands of lives per year. A clustered, randomized trial in India compared one-time cervical visual inspection and immediate colposcopy, biopsy, and/or cryotherapy (where indicated) versus counseling on cervical cancer deaths in women aged 30 to 59 years. This was the first prospective randomized clinical trial to evaluate cervical cancer screening.

45. Ovarian cancer screening Modalities proposed for ovarian cancer screening include the bimanual pelvic examination, serum CA-125 antigen measurement and transvaginal ultrasound (TVU). CA-125 It is neither sensitive nor specific. It is elevated in only approximately half of women with ovarian cancer and may be elevated in a number of non malignant diseases (e.g., diverticulosis, endometriosis, cirrhosis, normal menstruation, pregnancy, and uterine fibroids). TVU It has shown poor performance in the detection of ovarian cancer in average and high risk women

46. Recommendations No organization currently recommends screening average-risk women for ovarian cancer. In 2012, the USPSTF recommended against screening for ovarian cancer , concluding that there was “adequate evidence” that screening for ovarian cancer can lead to important harms, mainly surgical interventions in women without ovarian cancer National Institutes of Health (NIH) consensus panel concluded that it was prudent for women with a known hereditary ovarian cancer syndrome, such as BRCA1/2 mutations or hereditary nonpolyposis colorectal cancer (HNPCC), to have annual rectovaginal pelvic examinations, CA-125 determinations, and TVU until childbearing is completed or at least until age 35 years, at which time prophylactic bilateral oophorectomy is recommended

47. Endometrial Cancer Screening There is insufficient evidence to recommend endometrial cancer screening either for women at average risk or for those at increased risk due to a history of unopposed estrogen therapy, tamoxifen therapy, late menopause, nulliparity, infertility or failure to ovulate, obesity, diabetes, or hypertension The ACS recommends that women be informed about the symptoms of endometrial cancer, in particular, vaginal bleeding and spotting, after the onset of menopause. Women should be encouraged to immediately report these symptoms to their physician. Women at high risk (e.g., Lynch syndrome) should consider undergoing annual endometrial biopsy to evaluate endometrial histology beginning at age 35 years. This is based on expert opinion.

48. LUNG CANCER SCREENING Lung cancer screening programs using chest radiographs (chest x-ray) and sputum cytology began in the late 1940s. Various studies showed no benefit LDCT - Low Dose CT- 1.5mSv in 15 sec vs 8mSv in few mins The largest, longest and first to report a mortality end point is the National Lung Screening Trial (NLST). Approximately 53,000 persons were randomized to receive three annual LDCT scans or single-view posteroanterior chest x-rays 20% reduction in lung cancer

49. Recommendations Following the announcement of the NLST results, the ACS, American College of Chest Physicians (ACCP), American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) recommended that clinicians should initiate a discussion about lung cancer screening with patients who would have qualified for the trial; that is, those with the following characteristics: Aged 55 to 74 years At least a 30-pack-year smoking history Currently smoke or have quit within the past 15 years Recommendation : Once in 3 years LDCT

50. Prostate cancer Hugh Hampton Young first advocated early detection of prostate cancer with a careful digital rectal examination (DRE) in 1903. Screening for prostate cancer with the DRE and serum prostate-specific antigen (PSA) was first advocated in the mid 1980s and became common by 1992. PSA screening is directly responsible for prostate cancer becoming the most common nonskin cancer in American men.

51. Prostate guidelines American urology association – 2013 No screening for - < 4o years, average risk men 40-54 years and older than 70 years. Men 55- 69 years- informed consent about the PSA pro and cons. Transrectal biopsy – morbidity, infection

52. Skin cancer Melanoma No randomized trial Recommendations : Based of expert opinion ACS – Monthly self examination Yearly – clinically examination USPSTF – no evidence for routine screening