Thursday, December 18, 2008

Locally Advanced Cervical Cancer

AC presents a case of Locally Advanced Cervical Cancer.

Case: 42yo G4P3 woman presenting with hx of 3mo vaginal bleeding, and discharge. Biopsy positive for moderately differentiated SCC of the cervix. On exam, 5cm exophytic mass noted with parametrial involvement; cervix was fixed the sidewall. On PET, multiple Pelvic nodes were positive.

2nd most common cancer worldwide, with a predominance in south america, africa and south asia. In the US, it is the 6th most common (11,150 new cases in 2007), largely due to the widespread implementation of Pap testing.

Risk factors: HPV 16, 18 (E6 and E7 act on p53 and the Rb protein). Smoking, immunosuppression also associated. Prenatal DES is associated with clear cell adenocarcinoma.

Likely the incidence of cervical cancer will decrease with the increasing penetrance of the HPV vaccines.

Brief FIGO Staging Basics: IA microscopic, IB1 visible <=4cm, IB2 >4cm, IIA proximal vagina, IIB parametrium, IIIA distal 1/3 vagina, IIIB pelvic sidewall (including hydronephosis), IV involvement of bladder or rectum. Primarily a clinical staging system. Only exam and IVP may be used to stage, though hydronephrosis on CT can also be used to obtain IIIB. Stage IV diagnosis can only be arrived at after cysto or procto with biopsy proven involvement.

Of course, when determining treatment, one uses all of the information available including PET, CT, MRI and other modalities not included in the FIGO system.

1. Hreshcyshyn IJROBP 1979: IIIB, IVa, n=104, randomized to XRT+brachy +/- HU. Improved median survival 20 vs 11mos.

2. GOG85 IIB-IVa n=388 Whitney JCO 1999, XRT+brachy with HU vs 5FU/CDDP. All patients had operative nodal evaluations. PFS 57 vs 47%, OS 55 vs 43%, SS with one-tailed test.

3. RTOG 9001: Eifel JCO 2004 (update). IIB-IVA or IB-IIA >=5cm or positive nodes. EFRT (WPRT + PA nodes) vs WPRT with CDDP(75mg/m2)/5FU x 2, n=405. 8yr OS benefit: 67 vs 41% (SS), including local control, and DFS.

4. GOG 120: Rose JCO 2007 (update). IIB-IVA, n=526. XRT with CDDP (40 mg/m2) weekly, CDDP(50 mg/m2)/5FU/HU x 2, or HU twice weekly. Both CDDP arms were superior with 10yOS 53% vs 34% in HU arm, PFS and LC similarly improved (all SS).

5. GOG 109/Intergroup: Peters JCO 2000. IA2-IIA n=268, undergoing Rad Hyst and LND, with +LN, +parametrium, +margins randomized to RT vs RT+CDDP/5FU. 4yOS 71 vs 81%, with PFS benefit as well 63 vs 80%, all SS.

6. GOG 71: Keys 2003. IB2 (n=256) all underwent CTRT, randomized to observation vs TAH (doses of RT were slightly different between arms, 40Gy WPRT + 40Gy to pt A in the non-operative arm, 45Gy WPRT then 30Gy to pt A in the operative arm). 5y LC 27 vs 14% (no statistical significance). No PFS or OS advantage.

7. GOG 123: Keys NEJM 1999. IB2 (n=369), RT vs RT/CDDP then TAH. CDDP improved, OS (3yr 74 vs 83%), DFS, LC, all SS.

8. NCIC (Pearcey JCO 2002): n=253 IB-IVA. RT vs RT+CDDP (40mg/m2 weekly). 5yr OS 62 vs 58% (NS), no difference in PFS or LC. This is the outlier and reasons for why this trial is divergent remains a subject of debate.

Probably, however, it's simply due to a power issue as described during conference by DK and DB. I'm going to describe this in a separate post.

The approach at Duke is to treat with WPRT to 45Gy in 1.8Gy/fx, with weekly CDDP at 40mg/m2. This is followed by a brachytherapy boost via T&O to a total dose to point A of 75-85Gy. In this patient the PA nodes were treat in the initial fields (4field) and the boost was followed by a side wall boost of an additional 9 Gy.

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