Funded by: The Danish Cancer Society
Risk of cancer and repeated urgent referral - after a negative investigation for cancer
Ninna Nielsen, MD
Professor Peter Vedsted
Henry Jensen, PhD
Funded by: The Danish Cancer Society
General Practice:Patients with
symptoms/signs that could indicate disease
Referral to the non-specific signs and symptoms CPP
Blood panel
Referral to an organ specific standardized Cancer Patient
Pathway (CPP)
“Easy” access to diagnostic investigations
Organ-specificCPP
Diagnostic Centre
General practice holds responsibility for patient Hospital holds responsibility
Vedsted, Olesen., Br J Cancer. 2015
Cancer diagnostics in Denmark - schematic
Funded by: The Danish Cancer Society
Danish Cancer Patient pathways (CPPs)
• 28 organ-specific CPPs• Implemented in 2008/09
• Revised in 2016
• Uniform and more timely diagnosis and treatment of cancer
• Descriptions of selected symptoms that may raise cancer suspicion
• Descriptions of medical procedures (secondary health-care sector)
• Time frames for all phases
Funded by: The Danish Cancer Society
Danish CPP UK (urgent referral / 2WW)
Referral criteria All patients above 40:
Rectal bleeding
Change in bowel habit for 4 weeks
Unexplained haemorrhage anaemia
Significant general symptoms (e.g.
weight loss, stomach pain)
All patients as follows:
Aged 40 or older with unexplained weight loss AND
abdominal pain
Age 50 or older with unexplained rectal bleeding
Aged 60 with iron-defiency anaemia OR changed
bowel habits
Positive test for occult blood in faeces
Referral time 9 days 14 days (2 weeks)
Hospital diagnostics
(complete)
18 days n/a
Total time
(referral to treatment)
37 days (operation, chemotherapy)
41 days (radiotherapy)
62 days
Danish CRC-CPP vs. UK’s NICE guidelines
NICE. NICE Guideline no.12 - Suspected cancer: recognition and referral, 2015 Danish National Board of Health. Integrated Cancer Patient Pathway – Colorectal Cancer, 2016
Funded by: The Danish Cancer Society
Any problems?
• Difficult task for the GP to identify the patients who might have cancer
• Alarm symptoms of cancer are highly prevalent among patients
(Nielsen et al. Ugeskr Laeger 2010; Elnegaard et al. BMC Pub Health 2015)
• A single alarm symptom has low positive predictive value (PPV) for cancer
(Hamilton. Br J Cancer 2009)
• 40-50% of cancer patients present with vague non-specific symptoms (Jensen et al BMC Cancer 2014; Nielsen et al. Ugeskr Laeger 2010)
• Difficult for the GP to choose the correct organ-specific CPP
• 88% of cancers are diagnosed through at least oneCPP (Danish Health Data Agency 2016)
• Unknown how many?
Symptom at first consultation %
Alarm symptom 50
Serious, unspecific 15
Vague, non-specific 35
Jensen et al. BMC Cancer 2014; Nielsen el al. Ugeskr Læger. 2010; Hvidberg et al. [in preparation]
Funded by: The Danish Cancer Society
Aims
1. To estimate the proportion of patients who underwent a second CPP and were diagnosed with cancer- within six months after ending an initial CPP with a negative diagnosis
2. To investigate potential overlaps between the CPPs patients were referred to
Funded by: The Danish Cancer Society
The study
• Cohort study • Danish national registries • Six months follow-up
• Eligible patients:• Completed a first-time CPP with no verified cancer diagnosis• 1 January 2014 - 30 June 2015
• Outcomes• Second CPP• Subsequent cancer diagnosis
• During second CPP• Overall
• Death (not presented today)
Funded by: The Danish Cancer Society
Patients included
Male Female Total
n (%) n (%) n (%)
Total 48,653 (44.2) 61,345 (55.8) 109,998 (100)
Age group (years)
18-44 6,961 (14.3) 12,865 (21.0) 19,826 (18.0)
45-54 8,342 (17.1) 13,672 (22.3) 22,014 (20.0)
55-64 11,789 (24.2) 12,935 (21.1) 24,724 (22.5)
65-74 13,512 (27.8) 13,111 (21.4) 26,623 (24.2)
75-84 6,757 (13.9) 7,046 (11.5) 13,803 (12.5)≥85 1,292 (2.7) 1,716 (2.8) 3,008 (2.7)
Funded by: The Danish Cancer Society
First CPP with negative cancer test result- by anatomical site
Anatomical site of CPP Male Female Totaln (%) n (%) n (%)
Gastrointestinal (GI) system 19,139 (39.3) 20,300 (33.1) 39,439 (35.9)Breast 481 (1.0) 15,666 (25.5) 16,147 (14.7)Urinary system 8,541 (17.6) 4,232 (6.9) 12,773 (11.6)Lung 6,888 (14.2) 5,832 (9.5) 12,720 (11.6)Female cancers 7,077 (11.5) 7,077 (6.4)Head and neck 3,266 (6.7) 3,364 (5.5) 6,630 (6.0)Male cancers 6,401 (13.2) 6,401 (5.8)Melanoma, malignant 1,895 (3.9) 2,560 (4.2) 4,455 (4.1)CNS (brain) 1,018 (2.1) 1,374 (2.2) 2,392 (2.2)Lymphatic and blood systems 610 (1.3) 516 (0.8) 1,126 (1.0)Others 414 (0.9) 424 (0.7) 838 (0.8)
Funded by: The Danish Cancer Society
What happens within 6 months
CANCER diagnoses Totaln (%)
Total 693 (0.6)Men 303 (0.6)Women 390 (0.6)
Additional CPPs Total Men Womenn (%) n (%) n (%)
1 6,130 (5.6) 2,972 (6.1) 3,158 (5.1)2 517 (0.5) 270 (0.6) 247 (0.4)≥3 50 (0.0) 22 (0.0) 28 (0.0)
Total 6,697 (6.1) 3,264 (6.7) 3,433 (5.6)
Funded by: The Danish Cancer Society
Initial CPP Second CPPn n (%) most prevalent New cancer2
N (%) n (%)3
GI 39,439 2,782 (7.1) GI 1,386 (49.8) 112 (4.0)Breast 16,147 352 (2.2) GI 123 (34.9) 19 (5.4)Urinary system 12,773 817 (6.4) GI 348 (42.6) 40 (4.9)Lung 12,720 908 (7.1) GI 357 (39.3) 37 (4.1)Female cancers 7,077 521 (7.4) GI 205 (39.3) 27 (5.2)Head and neck 6,630 673 (10.2) Lymphatic & blood 262 (38.9) 35 (5.2)Male cancers 6,401 249 (3.9) Urinary system 117 (47) 8 (3.2)Melanoma malignant 4,455 83 (1.9) GI 28 (33.7) 6 (7.2)CNS (brain) 2,392 113 (4.7) Lung 38 (33.6) <5 n/a1
Lymphatic & blood 1,126 126 (11.2) Lymphatic & blood 32 (25.4) 7 (5.6)Others 838 73 (8.7) Lymphatic & blood 30 (41.1) <5 n/a1
Overall 109,988 6,697 (6.1) GI 2,782 (41.5) 295 (4.4)
Second CPP within 6 months? – how many? – which ones? – cancers?
Funded by: The Danish Cancer Society
Initial CPP Second CPPn n (%) most prevalent New cancer2
N (%) n (%)3
GI 39,439 2,782 (7.1) GI 1,386 (49.8) 112 (4.0)Breast 16,147 352 (2.2) GI 123 (34.9) 19 (5.4)Urinary system 12,773 817 (6.4) GI 348 (42.6) 40 (4.9)Lung 12,720 908 (7.1) GI 357 (39.3) 37 (4.1)Female cancers 7,077 521 (7.4) GI 205 (39.3) 27 (5.2)Head and neck 6,630 673 (10.2) Lymphatic & blood 262 (38.9) 35 (5.2)Male cancers 6,401 249 (3.9) Urinary system 117 (47) 8 (3.2)Melanoma malignant 4,455 83 (1.9) GI 28 (33.7) 6 (7.2)CNS (brain) 2,392 113 (4.7) Lung 38 (33.6) <5 n/a1
Lymphatic & blood 1,126 126 (11.2) Lymphatic & blood 32 (25.4) 7 (5.6)Others 838 73 (8.7) Lymphatic & blood 30 (41.1) <5 n/a1
Overall 109,988 6,697 (6.1) GI 2,782 (41.5) 295 (4.4)
Second CPP within 6 months? – how many? – which ones? – cancers?
Funded by: The Danish Cancer Society
Initial CPP Second CPPn n (%) most prevalent New cancer2
n (%) n (%)3
GI 39,439 2,782 (7.1) GI 1,386 (49.8) 112 (4.0)Breast 16,147 352 (2.2) GI 123 (34.9) 19 (5.4)Urinary system 12,773 817 (6.4) GI 348 (42.6) 40 (4.9)Lung 12,720 908 (7.1) GI 357 (39.3) 37 (4.1)Female cancers 7,077 521 (7.4) GI 205 (39.3) 27 (5.2)Head and neck 6,630 673 (10.2) Lymphatic & blood 262 (38.9) 35 (5.2)Male cancers 6,401 249 (3.9) Urinary system 117 (47) 8 (3.2)Melanoma malignant 4,455 83 (1.9) GI 28 (33.7) 6 (7.2)CNS (brain) 2,392 113 (4.7) Lung 38 (33.6) <5 n/a1
Lymphatic & blood 1,126 126 (11.2) Lymphatic & blood 32 (25.4) 7 (5.6)Others 838 73 (8.7) Lymphatic & blood 30 (41.1) <5 n/a1
Overall 109,988 6,697 (6.1) GI 2,782 (41.5) 295 (4.4)
Second CPP within 6 months? – how many? – which ones? – cancers?
Funded by: The Danish Cancer Society
Initial CPP Second CPPn n (%) most prevalent New cancer
n (%) n (%)GI 39,439 2,782 (7.1) GI 1,386 (49.8) 112 (4.0)Breast 16,147 352 (2.2) GI 123 (34.9) 19 (5.4)Urinary system 12,773 817 (6.4) GI 348 (42.6) 40 (4.9)Lung 12,720 908 (7.1) GI 357 (39.3) 37 (4.1)Female cancers 7,077 521 (7.4) GI 205 (39.3) 27 (5.2)Head and neck 6,630 673 (10.2) Lymphatic & blood 262 (38.9) 35 (5.2)Male cancers 6,401 249 (3.9) Urinary system 117 (47) 8 (3.2)Melanoma malignant 4,455 83 (1.9) GI 28 (33.7) 6 (7.2)CNS (brain) 2,392 113 (4.7) Lung 38 (33.6) <5 n/aLymphatic & blood 1,126 126 (11.2) Lymphatic & blood 32 (25.4) 7 (5.6)Others 838 73 (8.7) Lymphatic & blood 30 (41.1) <5 n/aOverall 109,988 6,697 (6.1) GI 2,782 (41.5) 295 (4.4)
Second CPP within 6 months? – how many? – which ones? – cancers?
Funded by: The Danish Cancer Society
Conclusion
• 6% are re-referred to a new organ-specific CPP• Many concern the same anatomical area as the first CPP. • Particularly patients who are initially referred to a GI CPP
seem prone to be re-referred to a GI CPP.
• Referral to a second CPP has a PPV of 4.4% for finding cancer• Some cancers may be missed in the first CPP!• Cancer diagnosis delayed
Is a more broad CPP/urgent referral route needed?- e.g. a gastrointestinal (GI) CPP?