Cervical cancer 10 2011

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This is a comprehensive overview of Cervical cancer: Diagnosis, staging and treatment

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Cervical cancer 10 2011

  1. 1. Ahmed Zeeneldin
  2. 2. Anatomy Ahmed Zeeneldin 2
  3. 3. Incidence— Worldwide: — Third incidence (~500, 000 anually) — Second cause of cancer death (~ 275, 000) — 75% of cases occur in developing countries — Why incidence is low in developed countries? — Screening Ahmed Zeeneldin 3
  4. 4. NCI-Egypt Ahmed Zeeneldin 4
  5. 5. Risk factors— HPV: most important — High incidence areas: HPV 10-20% — Low incidence areas: HPV 5-10% — Immunization: — Gardasil FDA approved in 2006 — Cervarix— Other: — Smoking, parity, contraceptive use, — Early coitus, many sexual partners, history of STDs — chronic immunosuppression Ahmed Zeeneldin 5
  6. 6. HPV and cervical cancer Ahmed Zeeneldin 6
  7. 7. Vaccination Against HPV— Gardasil and Cervarix (C>G)— Protein of HPV 6, 11, 16, 18 (G) 16, 18 (C)— 3 IM injections over 6 Months (G 0,2,6), (C 0,1,6)— Age — most effective if given before sexual intercourse is initiated — Girls and women ages 9 -26 years — Not recommended for older than 26 years. — Best for 11-12 years— Effectiveness after 3 years (no CIN): — No prior HPV infection: 99% — Prior HPV infection: 44%— Why to continue screening? — Not all HPV strains — Not 100% effective— Males: — Penile cancer and anal cancer Ahmed Zeeneldin 7
  8. 8. Screening— Age: — 3 years after onset of vaginal intercourse — No later than 21 years — Till 70 y— Methods: — Cytology: — conventional smears annually — liquid based every 2 y — HPV DNA testing: for age >30 y — Every 3 y in combination with cytology if –ve — If +ve at the discretion of the physician— HPV vaccination: screened as usual, why? Ahmed Zeeneldin 8
  9. 9. Cytology needed— Uterine cervix is accessible to physician— Histology is needed 1. Cervical cytology or 2. Papanicolaou (Pap) smears or 3. Cervical biopsy 4. Cone biopsy: if others are inadequate or if degree of invasion needed. Ahmed Zeeneldin 9
  10. 10. Cervical (pap) smear Ahmed Zeeneldin 10
  11. 11. Cone biopsy Ahmed Zeeneldin 11
  12. 12. CT Parametrial extension Pelvic wall extension Bladder and rectum and uerter encasement invasion Ahmed Zeeneldin 12
  13. 13. Ahmed Zeeneldin 13
  14. 14. Ahmed Zeeneldin 14
  15. 15. Figure 2. Clinical and imaging stage IIIB cervical cancer in a 37-year-old woman with hydronephrosis at diagnosis Pannu H K et al. Radiographics 2001;21:1155-1168©2001 by Radiological Society of North America
  16. 16. Figure 4. Tumor extension into the vagina in a 50-year-old woman with clinical stage IIIB and imaging stage IIIA cervical cancer Pannu H K et al. Radiographics 2001;21:1155-1168©2001 by Radiological Society of North America
  17. 17. Histology— Normal epithelial lining of cervix— Cancer: — Squamous cell carcinoma (80%) — Adenosquamous — Adenocarcinoma — Others : — Neuroendocrine carcinoma, — small cell tumors, — glassy-cell carcinomas, — sarcomas, Ahmed Zeeneldin 17
  18. 18. Clinical picture— Asymptomatic— Watery vaginal discharge— Postcoital bleeding or— Intermittent spotting. Ahmed Zeeneldin 18
  19. 19. Workup— History and physical examination— Routine lab: — CBCD, liver and renal function tests.— Radiologic imaging : — Chest x-ray, CT, MRI, or PET;— Cystoscopy and proctoscopy examination under anesthesia Ahmed Zeeneldin 19
  20. 20. Staging of cervical CA T1=FI (T2=FII) (T3=FIII) (T4=FIVA) N1 M1=FIVBConfined to uterus Outside uterus but not T3 Outside uterus to Outside uterus to: Regional Distant spreadA: Microscopic A: Parametrium negative A: Vagina lower 1/3 A: Bladder or LN Including A1: 7H x 3D mm A1: <= 4 cm B: Pelvic wall, rectal mucosa peritoneal A2: 7H x 5D mm A2: > 4 cm Causing HN of NFK B: ExtrapelvicB: Macroscopic B: Parametrium positive extension B1: <= 4 cm B2: > 4 cm No stage grouping F =FIGO stage HN:hydronenphrosis NFK: non-functioning kidney M1=FIVB Ahmed Zeeneldin 20
  21. 21. Treatment modalities— Surgery: — Limited: radical trachelectomy for tumors up to 2 cm if fertility preservation is desired — Extensive: radical hystrectomy +/- pelvic +/- PA LND— Concomitant chemo-radiotherapy; CCRT: (Cisplatin)— Palliative chemotherapy: cisplatin-based— BSC Ahmed Zeeneldin 21
  22. 22. Treatment of Cx CAStage stage Surg CCRT ChemoLocalized micro IA1 Micro 7Hx3D Yes* No No micro IA2 Micro 7H x 5D Yes* ORà RT alone** No <=4cm IB1 <=4cm Yes * ORà RT alone** No IIA1 Parmet -/ <=4cm >4cm IB2 >4cm Yes ORà CCRT*** No IIA2 Parmet -/ >4cmLocally IIB Paramet + No CCRT Noadvanced IIIA/B LVag/Pel W IVA Blad/Rect/HNMetastatic IVB Mets No No Pall’tve * Surgery can be extensive or limited for fertility preservation *Post op CCRT can be given in : LN+, SM+, Parametrium + ** No surgery after CCRT *** adjuvant surg can be done after CCRT Ahmed Zeeneldin 22
  23. 23. Surgery and CCRT— If surgery was used first: — Post op CCRT can be given to high risk patients: — positive lymph nodes, or — parametrial extension, or — positive margins)— If CCRT was used first: surgery is not recommended Ahmed Zeeneldin 23
  24. 24. RT and surgery are equal inTreatment of stage IB and IIA RT Surgery IB & IIA 171 172 *(PO RT to => pIIB ~ 100 pt) 5-y DFS 74% 74% 5-y OS 83% 83% Recurrence 26% 25% Severe morbidity* 19% 28%— Landoni Eet al, Lancet. 1997 Aug 23;350(9077):535-40. Ahmed Zeeneldin 24
  25. 25. Concurrent CRT— CCRT — Improves DFS and OS compared to RT alone or RT+HU— Cisplatin : standard — 40 mg/sm weekly up to 6 weeks (Max 70 mg) — Less toxic than 5FU/Cisplatin— Cisplatin and 5FU: more toxic — 3 cycles: — (1st and 2nd )D1-5, D22-26: during EBRT — (3rd ) D1-5 during second brachytherapy course — Cisplatin 20 mg/sm/d x 5 d, FU 1000 mg/sm/d x 5d— 5FU alone is not optimal— Intolerance to ciaplatin: àcarboplatin or xeloda — Cb: 100mg/m or UC 2 weekly— Novel regimen: weekly x 6 CCRT à adjuvant gem cis — CCRT: Cisplatin 40 mg/sm followed by Gem 125 mg/m2 — Adj: Gem (1,000 mg/m2 on Days 1 and 8) plus Cis (50 mg/m2 on Day 1) x 2 cycles q 21 d Ahmed Zeeneldin 25
  26. 26. Adding Gemcitabine to cisplatin inCRT— Dueñas-González et al, 2011, JCO— Patients and Methods Eligible chemotherapy- and radiotherapy-naive patients with stage IIB to IVA disease and Karnofsky performance score ≥ 70 were randomly assigned to:— arm A (cisplatin 40 mg/m2 and gemcitabine 125 mg/m2 weekly for 6 weeks with concurrent external-beam radiotherapy [XRT] 50.4 Gy in 28 fractions, followed by brachytherapy [BCT] 30 to 35 Gy in 96 hours, and then two adjuvant 21-day cycles of cisplatin, 50 mg/m2 on day 1, plus gemcitabine, 1,000 mg/m2 on days 1 and 8) :— or to arm B (cisplatin and concurrent XRT followed by BCT only; dosing same as for arm A) Ahmed Zeeneldin 26
  27. 27. — Results Between May 2002 and March 2004, 515 patients were enrolled (arm A, n = 259; arm B, n = 256).— PFS at 3 years was significantly improved in arm A versus arm B (74.4% v 65.0%, respectively; P = .029),— as were overall PFS (log-rank P = .0227; hazard ratio [HR], 0.68; 95% CI, 0.49 to 0.95),— overall survival (log-rank P = .0224; HR, 0.68; 95% CI, 0.49 to 0.95),— and time to progressive disease (log-rank P = .0012; HR, 0.54; 95% CI, 0.37 to 0.79).— Grade 3 and 4 toxicities were more frequent in arm A than in arm B (86.5% v 46.3%, respectively; P < .001), including two deaths possibly related to treatment toxicity in arm A. Ahmed Zeeneldin 27
  28. 28. CCRT is better than RT alone inStage IB2-IVA Ahmed Zeeneldin 28
  29. 29. CCRT is better than RT alone inBulky stage IB2 and IIA (=> 5cm) & IIB-IVA RT CCRT 193 193 5-y DFS 40% 67% (P<0.001) 5-y OS 58% 73% (P<0.004) Recurrences and mets higher Hem toxicity Higher but reversibel— Moris et al N Engl J Med. 1999 Apr 15;340(15):1137-43.— Conclusions: CCRT > RT— Cisplatin 20 mg/sm/d &FU 1000 mg/sm/d [x 5d x 3 courses] Ahmed Zeeneldin 29
  30. 30. CCRT is better than RT alone inBulky stage IB and IIA (=> 4cm) RT+Surgery CRT+Surgery 186 183 RR of progression 1 0.51 (P<0.001) RR of death 1 0.54 (P=0.008) G3-4 Hem Toxicity 2% 21% GI toxicity 5% 14%— Keys HM et al, N Engl J Med. 1999 Apr 15;340(15):1154-61.— Conclusions: CCRT > RT— Cisplatin 40 mg/sm q w x 6 max 70 mg Ahmed Zeeneldin 30
  31. 31. CCRT with cisplatin is standard inBulky stage IIB-IVA RT+ cisplatin RT+ cis+5FU+HU RT+HU SCC, adeno, `175 `175 ~175 AdenoSquamous PFS Higher (P<0.001) higher (P<0.001) Lower OS Higher (P=s) Higher (p=s) lower RR of progression 0.57 0.55 1 RR of death 0.61 0.58 1— Rose et al, N Engl J Med. 1999 Apr 15;340(15):1144-53.— Conclusions: CCRT > RT, Cis = cis/5FU > HU— Cis 40 mg/sm/w x 6— Cisplatin 50mg/sm d1 &FU 1000 mg/sm/d [x 4d x 2 courses] Ahmed Zeeneldin 31
  32. 32. Chemotherapy for Rec/mets— First-line combination therapy — Cisplatin/paclitaxel — Carboplatin/paclitaxel — Cisplatin/topotecan — Cisplatin/gemcitabine (category 2B)— Possible first-line single agent therapy — Cisplatin (preferred as a single agent) — Carboplatin — Paclitaxel Ahmed Zeeneldin 32
  33. 33. Chemotherapy for Rec/mets— Second-line therapy†† — Bevacizumab — Docetaxel — 5-FU (5-fluorouracil) — Gemcitabine — Ifosfamide — Irinotecan — Topotecan — Pemetrexed (category 3) — Vinorelbine (category 3 Ahmed Zeeneldin 33
  34. 34. Treatment of metastatic disease— Systemic chemotherapy and— Individualized radiotherapy. Ahmed Zeeneldin 34
  35. 35. Relapse— Locoregional— Systemic Ahmed Zeeneldin 35
  36. 36. Relapse— Locoregional therapy — After surgery: CCRT — After RT: possible surgery — After surgery and CCRT: platinum-based CT/BSC— Systemic therapy — Extrapelvic or para-aortic recurrence(s) at multiple sites or with unresectable recurrence — Platinum-based CT/BSC — Surgery has limited role for isolated sites Ahmed Zeeneldin 36
  37. 37. Palliative chemotherapy— Recurrent or metastatic disease— Not candidate for surgery or RT— Platinum-based (most active, RR 20-30%)— Compared with cisplatin: — Combinations : — Same QOL, little or no OS advantage — cisplatin/paclitaxel and — cisplatin/topotecan (category 1 for both) Ahmed Zeeneldin 37
  38. 38. Cisplatin-paclitaxel cispaltin Cisplatin - pacliatxel IVB recurrent or 134 130 persistent SCC RR (CR) 19 (6)% 36 (15)% Median PFS 2.8 m 4.8 m (P < .001) Median OS 8.8 m 9.7 m (PNS) QOL same same Anemia/neutropenia more— Moore et al, J Clin Oncol 2004;22:3113-3119 Ahmed Zeeneldin 38
  39. 39. Cisplatin- topotecan Cispaltin Cisplatin - topotecan 146 147 RR 13% 27% Median PFS 2.9 m 4.6 m (P=0.014) Median OS 6.5 m 9.4 m (P=0.017) QOL same same Anemia/neutropenia more — Long HJ et al, J Clin Oncol. 2005 Jul 20;23(21):4626-33. — Cis 50 mg/sm q 3w — Topo 0.75 mg/sm/d x 3 d q 3w — MVAC third arm was closed due to high mortality — Fisrt to show OS advantage Ahmed Zeeneldin 39
  40. 40. — PATIENTS AND METHODS:— RCT of 3 regimens every 3 weeks doses in mg/m2— paclitaxel 135 over 24 hours plus Cis 50 day 2 (PC);— vinorelbine 30 days 1 &8 plus Cis 50 day 1 (VC);— gemcitabine 1,000 day 1 &8 plus Cis 50 day 1 (GC);— topotecan 0.75 days 1, 2, &3 plus Cis 50 day 1 (TC). Ahmed Zeeneldin 40
  41. 41. Ahmed Zeeneldin 41
  42. 42. Ahmed Zeeneldin 42
  43. 43. Conclusions•VC, GC, and TC are not superior to PC in terms of overall survival (OS).•However, the trend in RR, PFS, and OS favors PC.•Differences in chemotherapy scheduling, pre-existing morbidity, and toxicity areimportant in individualizing therapy. Ahmed Zeeneldin 43

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