Radiation Oncology/Cervix/IA

Prognostic Factors

• Depth of stromal invasion (measured from base membrane of cervical epithelium)
  • <3 mm (IA1): Parametrial invasion rate 0 - 2.3%, LN mets rate 0 - 5.3%
  • >3 mm (IA2): Parametrial invasion rate 0 - 3.3%, LN mets rate 1.3 - 13.8% (average ~8%)
• Lymphovascular space invasion
  • Clinical significance is controversial
  • Strong correlation with depth of invasion and tumor volume; literature unclear if it is an independent prognostic factor
  • Nevertheless, many GYN/ONC do not consider patients with LVSI+ to be Stage IA (including SGO and JSOG definitions)
• Tumor volume
  • Clinical significance is controversial in IA
  • Some data support volumetric measurement, but technique is slow and imprecise
• Confluence of invasive foci
  • There appears to be no difference (FIGO vs. JSOG data)
• Grade
  • Four studies did not find grade an independent prognostic variable

Treatment Overview

• IA1 and LVSI-
  • Historically total hysterectomy a gold standard
  • Demonstration of minimal risk of parametrial spread and LN+, with significant morbidity, resulted in shift to conization
  • Cervical conization primary treatment today
  • Brachytherapy alone probably a reasonable option in non-surgical candidates, based on the 2 series below
  • NCCN.org:
    • Extrafascial hysterectomy or
    • Cone + observe if negative margins or
    • Modified radical + PLND if LVSI+
• IA2 or LVSI+
  • Some form of hysterectomy to evaluate parametrial space and LNs
  • NCCN.org:
    • Radical hysterectomy + PLND +/- aortic LN dissection or
    • Pelvic RT + brachytherapy (75-80 Gy to Point A)
    • Radical trachelectomy + LND if fertility preservation desired

Surgical Series

• Milan, 2005 (Italy) PMID 15670302 -- "Prognostic factors in microinvasive cervical squamous cell cancer: long-term results." (Raspagliesi F, Int J Gynecol Cancer. 2005 Jan-Feb;15(1):88-93.)
  • Retrospective. 67 patients with IA1 treated with conization. Mean F/U 10 years
  • Invasive recurrences: 4 patients (6%)
  • Predictive factors: LVSI+, cone apical margin distance <10mm

• Italian CTF, 2003 (Italy) PMID 14658592 -- "The clinical outcome of patients with stage Ia1 and Ia2 squamous cell carcinoma of the uterine cervix: a Cooperation Task Force (CTF) study." (Gadducci A, Eur J Gynaecol Oncol. 2003;24(6):513-6.)
  • Retrospective, multi-institutional. 166 patients with IA (143 patients IA1, 23 patients IA2), treated with conization alone (18%, all IA1), total hysterectomy (49%), or radical hysterectomy (33%).
  • Pelvic LN status: 0/67 LN+
  • Recurrence: 5% intraepithelial and 2% invasive. IA1 recurrence 6%, IA2 recurrence 13%. Cone alone 10% (but none invasive), total hysterectomy 5%, radical hysterectomy 9%
  • Conclusion: Conization can be a definitive treatement for Stage IA1. For Stage IA2, extrafascial hysterectomy might be adequate, need for LN dissection is questionable

• Oslo, 1989 PMID 2722048 -- "Follow-up study of 232 patients with stage Ia1 and 411 patients with stage Ia2 squamous cell carcinoma of the cervix (microinvasive carcinoma)." (Kolstad P, Gynecol Oncol. 1989 Jun;33(3):265-72.)
  • Retrospective. 643 patients with IA. Follow up 3-17 years
  • Surgery: recurrence 15/496 (3%). All salvaged with further surgery
  • Brachytherapy alone: recurrence 0/136 (0%)

Radiotherapy Series

• Washington University, 1991 (1959-1986) PMID 1905690 -- "Radiotherapy alone for medically inoperable carcinoma of the cervix: stage IA and carcinoma in situ." (Grigsby PW, Int J Radiat Oncol Biol Phys. 1991 Jul;21(2):375-8.)
  • Retrospective. 21 patients with CIS and 34 patients with IA.
  • RT for IA: BT alone (13 patients) to average 55 Gy to Point A, BT + Whole Pelvis (21 patients) to 14 Gy WP + 23.5 Gy parametrial boost with midline block + BT to 52 Gy to Point A
  • Recurrence: 0/21 CIS, 1/34 IA in pelvis. No DM.
  • Toxicity: severe complications 6%, in those getting WPRT + BT
  • Conclusion: BT alone excellent treatment for both CIS and IA

• Oslo, 1989 PMID 2722048 -- "Follow-up study of 232 patients with stage Ia1 and 411 patients with stage Ia2 squamous cell carcinoma of the cervix (microinvasive carcinoma)." (Kolstad P, Gynecol Oncol. 1989 Jun;33(3):265-72.)
  • Retrospective. 643 patients with IA. Follow up 3-17 years
  • Surgery: recurrence 15/496 (3%). All salvaged with further surgery
  • Brachytherapy alone: recurrence 0/136 (0%)

Review

• Milan, 2003 PMID 14693337 -- "Microinvasive squamous cell cervical carcinoma." (Raspagliesi F, Crit Rev Oncol Hematol. 2003 Dec;48(3):251-61.)