CES2019-01: Cáncer ginecológico III - Visión del oncólogo

Clase de cáncer de cérvix uterino, ovario y endometrio, con la perspectiva del oncólogo.

1. CES2019.01 – Cáncer ginecológico III – Visión del oncólogo Mauricio Lema Medina MD @Onconerd

2. Topics Cervical cancer Ovarian cancer Endometrial cancer

3. Objetivo Obtener un conocimiento GENERAL del manejo USUAL de pacientes con las patologías a discutir desde la sospecha diagnóstica, hasta el las pautas de seguimiento post-tratamiento, pasando por los aspectos más relevantes de tratamientos con intención curativa.

4. Cancer New cases (World) Deaths (World) New cases (Colombia) Deaths (Colombia) Breast 2’088.849 (2) 626.679 (5) 13.380 (1) 3.702 (4) Prostate 1’276.106 (4) 358.989 (8) 12.712 (2) 3.166 (5) Lung 2’093.876 (1) 1’761.007 (1) 5.856 (5) 5.236 (2) Stomach 1’033.701 (5) 782.685 (3) 7.419 (4) 5.505 (1) Colon & rectum 1’849.518 (3) 880.792 (2) 9.140 (3) 4.489 (3) Lymphoma (NH) 509.990 (10) 248.724 (11) 4.170 (6) 1.676 (10) Uterine cérvix 569.847 (8) 311.365 (9) 3.853 (7) 1.775 (9) Leukemia 437.003 (12) 309.006 (10) 3.126 (8) 2.192 (7) Ovarian 295.414 (17) 184.799 (14) 2.414 (9) 1.252 (11) Pancreas 458.918 (11) 402.232 (7) 2.311 (10) 2.142 (8) Liver 841.080 (6) 781.636 (4) 2.279 (11) 2.216 (6) Multiple mieloma 159.885 (21) 106.105 1323 (14) 806 (14) Esophagus 572.034 (7) 508.585 (6) 922 (15) 710 (15) Hodgkin 79.999 (25) 26.167 743 (16) 216 Brain 296.851 (16) 241.037 (12) 1884 (12) 1.176 (12) Gallbladder 219.420 (19) 165.087 (17) 1657 (13) 1.104 (13) All 18’078.957 9’555.027 101.893 46.057 http://gco.iarc.fr/today/

5. Cancer New cases (World) Deaths (World) New cases (Colombia) Deaths (Colombia) Breast 2’088.849 (2) 626.679 (5) 13.380 (1) 3.702 (4) Prostate 1’276.106 (4) 358.989 (8) 12.712 (2) 3.166 (5) Lung 2’093.876 (1) 1’761.007 (1) 5.856 (5) 5.236 (2) Stomach 1’033.701 (5) 782.685 (3) 7.419 (4) 5.505 (1) Colon & rectum 1’849.518 (3) 880.792 (2) 9.140 (3) 4.489 (3) Lymphoma (NH) 509.990 (10) 248.724 (11) 4.170 (6) 1.676 (10) Uterine cérvix 569.847 (8) 311.365 (9) 3.853 (7) 1.775 (9) Leukemia 437.003 (12) 309.006 (10) 3.126 (8) 2.192 (7) Ovarian 295.414 (17) 184.799 (14) 2.414 (9) 1.252 (11) Pancreas 458.918 (11) 402.232 (7) 2.311 (10) 2.142 (8) Liver 841.080 (6) 781.636 (4) 2.279 (11) 2.216 (6) Multiple mieloma 159.885 (21) 106.105 1323 (14) 806 (14) Esophagus 572.034 (7) 508.585 (6) 922 (15) 710 (15) Hodgkin 79.999 (25) 26.167 743 (16) 216 Brain 296.851 (16) 241.037 (12) 1884 (12) 1.176 (12) Gallbladder 219.420 (19) 165.087 (17) 1657 (13) 1.104 (13) All 18’078.957 9’555.027 101.893 46.057 http://gco.iarc.fr/today/

6. Cervical cancer

7. https://www.nccn.org

8. https://www.nccn.org

9. FIGO CANCER REPORT 2018 (Bhatla N. Int J Gynecol Obstetrics 2018; 143 (Suppl. 2): 22-36

10. Clinical suspicion Colposcopy and biopsy Suspicious cytology TNM/Stage

11. Workup Comment 1 Comment 2 H&P Colposcopy and biopsy Chest imaging In stage I: plain CXR, followed by CT if abnormal Consider pelvic MRI Preferred for FIGO stage IB2, and higher FDG PET-CT For FIGO stage IB2, II, III, and IVa.
Also consider after incidental cervical cancer after total hysterectomy In stage IB1 if fertility sparing desired Chest/abdomen/pelvic CT
(if PET-CT not available) For FIGO stage IB2, II, III, and IVa.
Also consider after incidental cervical cancer after total hysterectomy In stage IB1 if fertility sparing desired. Cervical cancer https://www.nccn.org

12. Clinical suspicion Colposcopy and biopsy Suspicious cytology TNM/Stage Early Locally-advanced Metastatic

13. Workup Comment 1 Comment 2 H&P Colposcopy and biopsy Chest imaging In stage I: plain CXR, followed by CT if abnormal Consider pelvic MRI Preferred for FIGO stage IB2, and higher FDG PET-CT For FIGO stage IB2, II, III, and IVa.
Also consider after incidental cervical cancer after total hysterectomy In stage IB1 if fertility sparing desired Chest/abdomen/pelvic CT
(if PET-CT not available) For FIGO stage IB2, II, III, and IVa.
Also consider after incidental cervical cancer after total hysterectomy In stage IB1 if fertility sparing desired. Cervical cancer https://www.nccn.org

14. SEER database, accessed 2019

15. Early cervical cancer

16. FIGO CANCER REPORT 2018 (Bhatla N. Int J Gynecol Obstetrics 2018; 143 (Suppl. 2): 22-36

17. Cervical cancer FIGO CANCER REPORT 2018 (Bhatla N. Int J Gynecol Obstetrics 2018; 143 (Suppl. 2): 22-36

18. FIGO CANCER REPORT 2018 (Bhatla N. Int J Gynecol Obstetrics 2018; 143 (Suppl. 2): 22-36 Cervical cancer

19. Stage IB: Confined to the cervix Depth more than 5 mm Width more than 7 mm

20. FIGO CANCER REPORT 2018 (Bhatla N. Int J Gynecol Obstetrics 2018; 143 (Suppl. 2): 22-36 Cervical cancer

21. Bulky Stage IB: Confined to the cervix More than 4 cm

22. FIGO CANCER REPORT 2018 (Bhatla N. Int J Gynecol Obstetrics 2018; 143 (Suppl. 2): 22-36 Cervical cancer Concurrent platinum-based radiotherapy

23. FIGO CANCER REPORT 2018 (Bhatla N. Int J Gynecol Obstetrics 2018; 143 (Suppl. 2): 22-36 Cervical cancer Concurrent platinum-based radiotherapy High-risk features : LVSI or invasion of the outer one-third of the cervical storm

24. Locally-advanced cervical cancer

25. Improved Treatment for Cervical Cancer — Concurrent Chemotherapy and Radiotherapy Thomas, G. M. (1999). Improved Treatment for Cervical Cancer ? Concurrent Chemotherapy and Radiotherapy. New England Journal of Medicine, 340(15), 1198–1200. https://doi.org/10.1056/NEJM199904153401509

26. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration. (2008). Reducing Uncertainties About the Effects of Chemoradiotherapy for Cervical Cancer: A Systematic Review and Meta-Analysis of Individual Patient Data From 18 Randomized Trials. Journal of Clinical Oncology, 26(35), 5802–5812. https://doi.org/10.1200/JCO.2008.16.4368

27. Cisplatino: 40 mg/m2/cada semana por 6 (Junto con teleterapia) Teleterapia (EBR) – Lunes a viernes, por 6-7 semanas - 4000-5000 cGY Braquiterapia (4000 -5000 cGy) 1 7 14 21 28 35 (Días)

28. FIGO CANCER REPORT 2018 (Bhatla N. Int J Gynecol Obstetrics 2018; 143 (Suppl. 2): 22-36 Cervical cancer Concurrent platinum-based radiotherapy

29. Stage Absolute 5-yr survival benefit Ib-IIa 10% IIb 7% III-IVa 3% Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration. (2008). Reducing Uncertainties About the Effects of Chemoradiotherapy for Cervical Cancer: A Systematic Review and Meta-Analysis of Individual Patient Data From 18 Randomized Trials. Journal of Clinical Oncology, 26(35), 5802–5812. https://doi.org/10.1200/JCO.2008.16.4368

30. FIGO CANCER REPORT 2018 (Bhatla N. Int J Gynecol Obstetrics 2018; 143 (Suppl. 2): 22-36 Cervical cancer

31. Post-operative radiation therapy (PORT)

32. High risk (any) Intermediate-risk (any two of three) Low-risk
(no high-risk factors, and only one of three) Positive margins Tumor size >4 cm Tumor size >4 cm LN metastases (N1) LVSI LVSI Parametrial spread Deep stromal invasion Deep stromal invasion

33. FIGO CANCER REPORT 2018 (Bhatla N. Int J Gynecol Obstetrics 2018; 143 (Suppl. 2): 22-36 Cervical cancer

34. Metastatic cervical cancer

35. FIGO CANCER REPORT 2018 (Bhatla N. Int J Gynecol Obstetrics 2018; 143 (Suppl. 2): 22-36 Cervical cancer

36. SEER database, accessed 2019

37. SEER database, accessed 2019

38. Cervical cancer surveillance interval history and physical examination every 3-6 mo for 2y, every 6-12 mo for 3-5 y, then annually based on patient’s risk of disease recurrence Cervical/vaginal cytology annually as indicated for the detection of lower genital tract neoplasia Imaging as indicate based on symptoms or examination findings suspicious for recurrence Laboratory assessment as indicated based on symptoms or examination findings suspicious for recurrence Patient education regarding symptoms of potential recurrence, periodic self-examinations, lifestyle, obesity, exercise, sexual health (including vaginal dilator use, lubricants/moisturizers, hormone replacement therapy), smoking cessation, nutrition counseling, and potential long-term and late effects of treatment https://www.nccn.org

39. Ovarian cancer

40. Ovarian Cancer Histologies Epithelial - 85% Older than 40 Serous 75% Mucinous 20% Bulky Differential diagnosis with Pseudomixoma Endometrioid 2% Others Clear cells Brenner Indifferentiated tumors Mixed histologies DeVita. Cancer: Principles and Practice of Oncology, 9 th Edition Diapositiva diseñada por Ana Milena Roldán, MD

41. HISTOLOGÍA CÁNCER DE OVARIO 5% GERMINALES 75% DE NEOPLASIAS OVÁRICAS MALIGNAS EN MUJERES <30 AÑOS TERATOMA QUÍSTICO Con frecuencia contienen cabellos, dientes y hueso calcificado . 1% malignos Struma ovárico DISGERMINOMA Equivalente al Seminoma del varón 10-15% bilaterales B- HCG y AFP OTROS: Tumor del Seno Endodérmico Carcinoma Embrionario Coriocarcinoma Gonadoblastoma DeVita. Cancer: Principles and Practice of Oncology, 9 th Edition Diapositiva diseñada por Ana Milena Roldán, MD

42. HISTOLOGÍA 10% ESTROMA OVÁRICO DE LA GRANULOSA Productor de estrógenos Ocasionan trastornos menstruales y pubertad precoz T. C. DE LEYDIG Y SERTOLI Productor de andrógenos Ocasionan virilización e hirsutismo TECOMAS Productor de estrógenos y andrógenos ANDROBLASTOMA Productor de andrógenos Primera causa de virilización de origen ovárico El patólogo también debe informar el grado de diferenciación: Grado I para los bien diferenciados y Grado III para los pobremente diferenciados. DeVita. Cancer: Principles and Practice of Oncology, 9 th Edition Diapositiva diseñada por Ana Milena Roldán, MD

43. Epithelial ovarian cancer

44. Abdominal distention Abdominal / Pelvic imaging Suspicious abdominal or pelvic mass Workup Ascites Non-specific Bloating Pelvic/abdominal pain Difficulty eating Feeling full quickly Urinary symptoms (urgency, frequency)

45. Workup H&P Abdominal / pelvic exam Ultrasound and CT/MRI as clinically indicated Chest CT or Chest X ray as clinically indicated Ca 125 or other tumor markers as clinically indicated Evaluate nutritional status GI evaluation as clinically indicated Obtain a family history Refer to gynecologic oncologist for clinically suspicious lesions Ovarian cancer https://www.nccn.org

46. https://www.nccn.org

47. https://www.nccn.org

48. Abdominal distention Abdominal / Pelvic imaging Suspicious abdominal or pelvic mass Ovarian cancer suspected Ascites Non-specific Bloating Pelvic/abdominal pain Difficulty eating Feeling full quickly Urinary symptoms (urgency, frequency) Surgical candidate Not a surgical candidate

49. SEER database, accessed 2019

50. Surgical candidate Stage IA or IB Grade 1 -Endometroid Surveillance Stage IA or IB Grade 3 or Clear Cell (some grade 2) Stages IC-IV Platinum-based chemotherapy Surveillance GOG 218 : Carboplatin + Paclitaxel +/- Bevacizumab (Stages III or IV)

51. Vergote (EORTC): Preoperative Carboplatin + Paclitaxel x2-3 months Not a surgical candidate Bulky stage III or IV disease. or poor surgical candidate Interval debunking surgery

52. SEER database, accessed 2019

53. SEER database, accessed 2019

54. Epithelial ovarian cancer surveillance Interval history and physical examination (including pelvic exam) every 2-4 mo for 2 y, then 3–6 mo for 3 y, then annually after 5 y Chest/abdominal/pelvic CT, MRI, PET/CT, or PET as clinically indicated Chest x-ray as indicated CBC and chemistry profile as indicated Ca-125 or other tumor markers if initially elevated Refer for genetic risk evaluation Long-term wellness care https://www.nccn.org

55. Criterios para investigación genética para cáncer hereditario Caso índice Ca ovario Ca páncreas Ca próstata metastásico Azkenazi + Ca mama Azkenazi + Ca próstata (Gleason ≥7) Ca mama ≤50 años Ca mama triple negativo ≤60 años Ca de mama x2 (primarios) NCCN, 2018

56. Criterios para investigación genética para cáncer hereditario Ca de mama, con ≥1 familiar cercano con: Caso índice Cáncer de mama ≤50 años Cáncer de ovario NCCN, 2018 Cáncer de mama en varón Cáncer de próstata de alto grado (Gleason ≥7) Cáncer de próstata metastásico ≥2 familiares con cáncer de mama

57. Criterios para investigación genética para cáncer hereditario Sin cáncer Caso índice Gen de susceptibilidad mutado en la familia Gen de susceptibilidad mutado en el individuo Individuo con familiar y 1er y 2ndo grado con: NCCN, 2018 Cáncer de mama ≤45 años Cáncer de ovario Cáncer de mama en varón Cáncer de próstata de alto grado (Gleason ≥7) Cáncer de próstata metastásico ≥2 familiares con Ca de mama, con uno ≤50 años ≥2 primarios de Ca mama en el mismo individuo

58. Criterios para investigación genética para cáncer hereditario Caso índice Individuo con familiares del mismo lado con ≥3: NCCN, 2018 Ca de mama, sarcoma, Ca adrenocortical, tumores cerebrales, leucemia Ca colon, Ca endometrio, Ca tiroides, Ca renal, cambios dermatológicos, macrocefalia, hamartomas gastrointestinales Ca lobulillar de mama, Ca gástrico difuso Ca mama, Ca gastrointestinal o pólipos hamartomatosos, Ca ovarianos (sex chords), Ca páncreas, Ca Sertoli, Childhood skin pigmantation Li-Fraumeni (p53) Cowden (PTEN) CIDH (E-Cadherin) STK

59. Criterios para investigación genética para cáncer de mama hereditario Cáncer de mama con cualquiera de los siguientes: Ca ovario Ca páncreas BRCA1/2 mutado en cualquier tumor Judía Azkenazi ≥2 Ca mama adicionales en pt/familia cercana Ca mama ≤50 años* Ca mama triple negativo ≤60 años Ca de mama x2 (primarios) NCCN, 2018 En la paciente con (cualquiera): *Otro cáncer de mama primario, historia familiar de cáncer de mama, historia familiar desconocida o limitada, o menor de 45 años Ca de mama ≤50 años Ca de ovario Ca de mama en varón Ca de próstata de alto grado (Gleason ≥7) Ca de próstata metastásico ≥2 familiares con cáncer de mama ≥1 familiar cercano con:

60. Endometrial cancer

61. nccn.org

62. nccn.org

63. SEER database, accessed 2019

64. SEER database, accessed 2019

65. Pure endometrial cancer Endometrioid

66. Total hysterectomy and bilateral salpingo-oophorectomy, and surgical staging No cervical involvement Total hysterectomy and bilateral salpingo-oophorectomy, and surgical staging Cervical involvement Preoperative External-beam RT

67. High-risk endometrial cancer Serous Clear cell Undifferentiated Dedifferentiated Carcinosarcoma

68. Total hysterectomy and bilateral salpingo-oophorectomy, and surgical staging High-risk histology Adjuvant systemic chemotherapy Adjuvant RT (stages IB-IV) + brachytherapy (All)

69. SEER database, accessed 2019

70. Drug MOA Included in Main toxicities Cisplatin Similar to alkylating agents (anti DNA agent) Chemo-RT
Single-agent metastatic
And, other protocols Renal dysfunction
Nausea/vomiting
Hypokalemia
Hypomagnesemia
Otic toxicity
Peripheral neuropathy Carboplatin Similar to alkylating agents (anti DNA agent) Adjuvant and first-line agent in ovarian and endometrial cancer Nausea/Vomiting
Myelosuppression
Thrombocytopenia Paclitaxel Microtubule poison GOG 240: Cisplatin + Paclitaxel + Bevacizumab
GOG 218: Ovarian cancer Joint pain
Myelosuppression
Peripheral neuropathy Bevacizumab Anti VEGF monoclonal antibody Metastatic cervical cancer - in first-line
Post surgery in high-risk stage III/IV ovarian cancer Hypertension
Bleeding
Delayed wound healing
Proteiunria