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Bending the Curve Trial by Trial
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Bending the Curve Trial by Trial

How medicine got from “there is no treatment” to today’s standard of care, one trial at a time.

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0%50%100%Schematic, not dataRegistry data

Dashed line: a schematic of how each new kind of treatment lifted the curve; it is not data. Solid line: 5-year relative survival, all cancers combined, by year of diagnosis, United States (SEER 8 registry areas) (People diagnosed with cancer of any site as defined by SEER Cancer Stat Facts, all races and both sexes, in the eight SEER 8 registry areas (Atlanta, Connecticut, Hawaii, Iowa, New Mexico, San Francisco-Oakland, Seattle-Puget Sound, Utah). Observed values by year of diagnosis, 1975 to 2018. The source page does not state the age range.). Relative survival estimates the share of people expected to survive the effects of their cancer, excluding the risk of dying from other causes. The eight registry areas do not cover the whole United States. The mix of cancers diagnosed may have changed over time, and earlier detection can raise measured survival through lead-time bias and overdiagnosis without changing how long people live. The curve shows what happened, not why. Values are the observed (not modeled) figures for each year of diagnosis. Needs review: the landmarks and figures here are not yet fully confirmed. Source

  1. 1600 BCE

    Oldest cited description of cancer

    The Edwin Smith papyrus, dated to about 1600 BCE, is cited as holding the oldest known description of cancer.

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  2. 400 BCE

    Hippocratic terms for cancer

    The word cancer is credited to Hippocratic physicians, who used karkinos for non-healing swellings and ulcers. Date approximate.

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  3. 1775

    An occupational link is described

    Percivall Pott described scrotal cancer in chimney sweeps, the first cancer linked to an occupational exposure.

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  4. 1846

    Ether anaesthesia enters surgery

    After the first public ether demonstration at Massachusetts General Hospital on 16 October 1846, surgical volume there rose.

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  5. 1858

    Cell theory enters pathology

    Virchow's Cellular Pathology (1858) gave cell theory clinical significance and changed the course of pathology.

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  6. 1894

    Radical mastectomy is described

    Halsted's 1894 report of breast cancer operations at Johns Hopkins described what became known as radical mastectomy.

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  7. 1896

    X-ray treatment of cancer: disputed origins

    Reports date X-ray treatment of cancer to 1896; priority is disputed, and one analysis favours Despeignes of Lyon (July 1896).

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  8. 1941

    Hormonal manipulation in prostate cancer

    In 1941 Huggins and Hodges studied castration, estrogen and androgen injection and serum phosphatases in metastatic prostate cancer.

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  9. 1941

    The Pap smear: a cell test for uterine cancer

    Papanicolaou and Traut's 1941 paper on the diagnostic value of vaginal smears in carcinoma of the uterus; the Pap test grew from this work.

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  10. 1946

    Nitrogen mustard: first lymphoma chemotherapy

    A Yale lymphoma patient treated in 1942 with a mustard-gas relative had tumours shrink, then return. Reports followed in 1946.

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  11. 1948

    Temporary remissions in childhood leukemia

    Farber and colleagues described temporary remissions in children with acute leukemia given a folic acid antagonist (aminopterin).

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  12. 1950

    Smoking is linked to lung cancer

    Doll and Hill compared London hospital patients with and without lung cancer: almost all the men with lung cancer had smoked.

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  13. 1963

    A randomized screening trial begins

    The HIP trial in New York began in December 1963, randomly assigning women aged 40 to 64 to a screening or a control group.

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  14. 1971

    Tamoxifen for advanced breast cancer

    A Manchester study gave an anti-oestrogen tablet to 46 postmenopausal women with advanced breast cancer; about 1 in 5 clearly responded.

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  15. 1977

    Cisplatin combination for testicular cancer

    50 patients with disseminated testicular cancer received cisplatin, vinblastine and bleomycin; about 3 in 4 assessed had complete remission.

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  16. 1981

    Less surgery for small breast cancers

    In a Milan trial of 701 patients with breast cancers under 2 cm, mastectomy and quadrantectomy plus radiotherapy gave similar survival.

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  17. 1983

    A papillomavirus found in cervical cancer

    Zur Hausen's team cloned a new papillomavirus, HPV 16, and found its DNA in 11 of 18 German cervical cancer samples.

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  18. 1988

    Vitamin A derivative induces leukemia remission

    All 24 people with acute promyelocytic leukemia had complete remission on all-trans retinoic acid (one with added cytarabine); 8 relapsed.

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  19. 1993

    Yearly stool tests lower bowel cancer deaths

    In a Minnesota trial of 46,551 people, yearly (not two-yearly) stool tests for hidden blood cut 13-year bowel cancer deaths by 33%.

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  20. 1998

    Trastuzumab targets HER2 in breast cancer

    On 25 September 1998 the US regulator approved trastuzumab for metastatic breast cancer whose tumours overexpress HER2.

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  21. 2001

    A kinase inhibitor in chronic myeloid leukemia

    In a phase 1 trial after interferon alfa had failed, the BCR-ABL inhibitor STI571 (imatinib) produced complete hematologic responses.

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  22. 2003

    The first human genome sequence is completed

    Launched in October 1990, the Human Genome Project finished in April 2003 with the first sequence of the human genome.

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  23. 2004

    EGFR mutations underlie gefitinib response

    EGFR mutations were found in 8 of 9 lung cancers that responded to gefitinib and none of 7 that did not; testing may find likely responders.

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  24. 2006

    A vaccine to prevent cervical cancer is licensed

    The US regulator licensed Gardasil on 8 June 2006 and called it the first vaccine developed to prevent cervical cancer.

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  25. 2010

    Anti-CTLA-4 antibody improves survival

    In a phase 3 trial in previously treated metastatic melanoma, ipilimumab improved overall survival compared with a gp100 vaccine alone.

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  26. 2011

    Low-dose CT screening for lung cancer

    In 53,454 people with a heavy smoking history, low-dose CT lowered lung-cancer deaths by 20% versus chest X-ray; false alarms were common.

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  27. 2012

    Anti-PD-1 antibody: responses in melanoma

    A phase 1 trial of an anti-PD-1 antibody found objective responses in 26 of 94 evaluable people with melanoma; some lasted a year or more.

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  28. 2014

    Engineered T cells for leukemia

    In pilot trials, CD19-directed CAR T cells produced complete remission in 27 of 30 children and adults with relapsed or refractory ALL.

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  29. 2017

    First approval by tumour feature, not organ

    In 2017 the US regulator approved pembrolizumab for MSI-H or dMMR solid tumours, its first approval by tumour feature, not site.

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  30. 2018

    Gene tests let some women skip chemotherapy

    Mid-range 21-gene score, no nodal disease: hormone therapy alone was non-inferior to adding chemotherapy; some women 50 or younger gained.

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  31. 2022

    An antibody-drug conjugate for HER2-low cancer

    In pretreated metastatic HER2-low breast cancer, trastuzumab deruxtecan lengthened progression-free and overall survival over chemotherapy.

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  32. 2022

    Teclistamab: a T-cell bispecific for myeloma

    In a single-arm phase 1-2 study, teclistamab gave a 63% response rate in 165 people with myeloma after at least three prior therapy lines.

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  33. 2026

    A RAS inhibitor in pancreatic cancer

    In 500 people with previously treated spread disease, median survival was about 13 months on daraxonrasib versus about 7 on chemotherapy.

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In the eight SEER registry areas of the United States, 5-year relative survival for all cancers combined rose from 49.85% for people diagnosed in 1975 to 73.58% for those diagnosed in 2018.

National Cancer Institute, Surveillance, Epidemiology, and End Results (SEER) Program. SEER Cancer Stat Facts: Cancer of Any Site. Bethesda, MD: National Cancer Institute; 2026. https://seer.cancer.gov/statfacts/html/all.html Source

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Digestive system

Urinary and male reproductive

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Gynecologic

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Skin

Bone, soft tissue and childhood tumours

The number beside each name is how many milestones its timeline holds.

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