Early stage cervical cancer Who does need radicality? RenĂŠ Pareja Gynecologic Oncologyst
No conflict of interest
Berkeley C, Bonney V. Br Med J. 1908 Oct 3;2(2492):961-7
Do they have the same natural history and prognosis:
1. Squamous cervical cancer after conization, 8 mm horizontal spread x 2 mm depth, Negative margins, negative ECC 2. Invasive Adenocarcinoma after conization,6 mm depth x 6 mm horizontal spread Negative margins, negative ECC
3. Cervical tumor, 4 cms diameter, without apparent parametrial involvement
IB1
“One size fits all�
Walter Kinney 1995 1956 to 1985
387 pts with cervical tumor
83 ( 21.4 % )
Stromal invasion > 3 mm 2 cms diameter LVSI ( - )
NO PARAMETRIAL INVOLVEMENT 5 years OS Author’s proposal
Gynecology oncology,57;3 – 6( 1995 )
97.6% (94.3 – 100 ) Modified radical hysterectomy + pelvic lymphadenectomy
Alan Covens 2002 1984 to 2000
842 patients, IA1 / IA2 / IB1
49 ( 6 % ) 33 ( 4 % )
Pelvic nodes ( + ) Parametrial involvement
TUMOR SIZE < 2 CMS, PELVIC NODES ( - ), DOI < 10 MM
Parametrial involvement 0.6% Gynecology oncology,84;145 - 149( 2002 )
Jason Wright 2007 1989 to 2005
594 early cervix cancer
64 ( 10.8 % )
PARAMETRIAL INVOLVEMENT
If negative nodes If positive nodes
Parametrial Involvement Parametrial involvement
4% ( 30 / 498 ) 47.9% ( 34 / 71 )
If negative nodes (-),Tx < 2 cms,LVSI (-) Parametrial involvement CANCER September 15, 2007 / Volume 110 / Number 6
0.4%
Tumors less than 2 cms diameter Negative LVSI Depth stromal invasion less than 10 mm Negative nodes
Parametrial Involvement
< 1- 2 %
Yang YC, Chang CL. Modified radical hysterectomy for early Ib cervical cancer. Gynecol Oncol.1999;74:241â&#x20AC;&#x201C;244. Magrina JF, Goodrich MA, Lidner TK, Weaver AL, Cornella JL, Podratz KC. Modified radical hysterectomy in the treatment of early squamous cervical cancer. Gynecol Oncol. 1999;72:183â&#x20AC;&#x201C;186.
T. Kato et al. / Gynecologic Oncology 137 (2015) 34â&#x20AC;&#x201C;39
T. Kato et al. / Gynecologic Oncology 137 (2015) 34â&#x20AC;&#x201C;39
Recurrence
5-year RFS 95.5% (95% CI, 92.5 to 97.3%) for cT ≤ 2 cm 87.1% (95% CI, 82.1% to 90.8%) for cT > 2 cm During the follow-up period, 45 patients recurred: 14 in the cT ≤ 2 cm group
31 in the cT > 2 cm group. Central recurrence 0.6% (2/323) of pts with cT ≤ 2 cm 4.8% (12/248) with cT > 2 cm. T. Kato et al. / Gynecologic Oncology 137 (2015) 34–39
Overall survival The 5-year OS was 95.8% (95% CI, 92.9 to 97.6%) in ≤ 2 cm and 91.9% (95% CI, 87.6% to 94.8%) in cT > 2 cm
T. Kato et al. / Gynecologic Oncology 137 (2015) 34–39
40 patients Two steps 6 pts (+) nodes 34 pts (-) nodes
Radical hysterectomy 10 IA2 large cone 24 IB1 simple trachelectomy Follow-up 47 months (12 â&#x20AC;&#x201C; 102) 1 relapse, no deaths 24/32 tried to get pregnant 23 pregnancies in 17 women
Gynecologic Oncology 132 (2014) 254â&#x20AC;&#x201C;259
Succesful procedures: 362 (93.7%) Reasons for rad hyst/chemo-radiotherapy: 17 positive nodes
2 positive margin 4 patientâ&#x20AC;&#x2122;s desire 1 deep stromal invasion + LVSI +
SUMMARY Nodal involvement: 4.7% LVSI: 31 (0-70%) Pregnancy rate among fertility preserved patients: 38.7% Relapse rate: 1%
Death rate: 0.2%
Fertility preservation rates ART
85.1%*
VRT
91.1%**
Simple cone/simple trach
93.7 %
*Pareja R, RendoĚ n GJ, Sanz-Lomana CM, Monzon O, Ramirez PT. Surgical, oncological, and obstetrical outcomes after abdominal radical trachelectomy.A systematic literature review. Gynecol Oncol 2013;131: 77â&#x20AC;&#x201C;82 **Ribeiro
Cubal AF, Ferreira Carvalho JI, Costa MF, Branco AP. Fertility-sparing surgery for early-stage cervical cancer. Int J Surg Oncol 2012;2012:936534
Pregnancy rates after fertility sparing procedures ART
16.2%*
VRT
24%*
Simple cone/simple trach
38.7 %
*Pareja R, RendoĚ n GJ, Sanz-Lomana CM, Monzon O, Ramirez PT. Surgical, oncological, and obstetrical outcomes after abdominal radical trachelectomy.A systematic literature review. Gynecol Oncol 2013;131: 77â&#x20AC;&#x201C;82
What’s next
Prospective ongoing trials
200/600
100
700
Gynecologic Cancer Intergroup. Radical vs simple hysterectomy and pelvic node dissection in patie nts with early stage cervical cancer. Clinical Trials.gov [Inter- net]. Bethesda (MD): National Library of Medicine (US); Oct 28 2000–2013 [Available from: http://clinicaltrials.gov/show/NCT01658930 NLM Identifier: NCT01658930]. Gynecologic Oncology Group. GOG Protocol 278 — studying the studying the physical function and quality of life before and after surgery in patients with stage I cervical cancer. Clinical Trials.gov [Internet]. Bethesda (MD): National Library of Medicine (US); Oct 28 2000–2013 [Available from: http://clinicaltrials.gov/show/ NCT01649089 NLM Identifier: NCT01649089]. M.D. Anderson Cancer Center. Conservative surgery for women with cervical cancer. Clinical Trials.gov [Internet]. Bethesda (MD): National Library of Medicine (US); Oct 28 2000–2013 [Available from: http://clinicaltrials.gov/show/NCT01048853 NLM Identifier: NTC01048853].
Gynecologic Oncology Group protocol 278. Multi-institutional trial PI Alan Covens “Evaluation of physical function and quality of life before and after non-radical surgical therapy (extrafascial hysterectomy or cone biopsy with pelvic lymphadenectomy) for stage IA1 (LVSI+) and IA2–IB1 (<2 cm) cervical cancer” SHAPE Trial PI Marie Plante
CON-CERV Trial PI Kathleen Schmeler
SHAPE Trial Simple Hysterectomy And Pelvic node dissection in Early cervix cancer Comparing radical hysterectomy and pelvic node dissection against simple hysterectomy and pelvic node dissection in patients with low risk cervical cancer Chair: Marie Plante University of Laval, Quebec City
An NCIC Clinical Trials Group proposal for the Gynecological Cancer Inter Group (GCIG)
Patient Population Stage IA2-IB1 Cervix cancer Squamous , Adeno & Adenosquamous ca < 2cm and < 50% stromal invasion Grades 1,2 & 3 MR/ CT node negative
RANDOMIZATION
Control Arm Radical Hysterectomy & PLND* +/- SLN Mapping**
Stratification Centers (SN mapping vs not) Mode of surgery (abd vs vaginal) Stage (IA2 vs IB1) Histology (squamous vs adenoca) Grade (1-2 vs 3)
Experimental Arm Simple Hysterectomy with Upper Vaginectomy & PLND* +/- SLN Mapping**
Post surgical quality of life & disease outcomes measured 3 monthly X 2 years, and 6 monthly for further 3 yrs
* PLND â&#x20AC;&#x201C; Pelvic lymph node dissection **SLN - Sentinel lymph node mapping optional
Protocol 2008-0118
CON-CERV
â&#x20AC;˘ Prospective, multi-center, international study â&#x20AC;˘ Objective: To evaluate the safety and feasibility of performing conservative surgery in women with early stage cervical cancer with favorable pathologic characteristics
Protocol 2008-0118
CON-CERV
Inclusion Criteria: • Stage IA2 or IB1 cervical cancer • Tumor diameter < 2 cm • No LVSI • Squamous cell histology (any grade) or adenocarcinoma (grade 1 or 2 only) • Cone margins and endocervical curettage (ECC) specimen negative for malignancy or adenocarcinoma in-situ and CIN II/III (one repeat cone/ECC permitted) • <10 mm stomal invasion Central pathology review is required
Protocol 2008-0118
CON-CERV
• Patients desiring future fertility undergo cone and pelvic lymph node dissection • Patients not desiring future fertility undergo simple hysterectomy and pelvic lymph • Lymphatic mapping is an optional procedure • Follow-up: pelvic exam and Pap test every 3 months • Quality of life questionnaires completed prior to surgery and a four time points following surgery
Protocol 2008-0118
CON-CERV
• Sample size: 100 patients • Stopping Rules: – Residual disease in the hysterectomy specimens of > 2 patients – If > 2 patients develop recurrent disease
CA CERVIX ESTADO I IA1
Menos 7 mm extensión horizontal Menos 3 mm profundidad
IA2
Menos 7 mm extensión horizontal Entre 3 y 5 mm profundidad
IB1
Mas de 7 mm extensión horizontal Mas de 5 mm profundidad Menos de 4 cms
IB2
Mas de 4 cms Sin compromiso parametrial
IB1a IB1b
Pos –conización Margenes negativos CEC negativo < 2 cms Infiltración < 10 mm CLV ? Todos los otros
Can we replace radical trachelectomy
with cone biopsy/simple trachelectomy/simple hysterectomy?
YES !
â&#x20AC;ŚUnder certain circumstancesâ&#x20AC;Ś
CONCLUSIONS Strict selection criteria Pathology review Experienced team Clinical trial