Surgical Oncology, SMS

1. Management of Carcinoma Cervix
Dr. Naina Kumar Agarwal
SR1 Surgical oncology
6.6.2021

2. Principles of Imaging

6. When in doubt, the lower staging should be
assigned.
• * Imaging and pathology can be used, where available, to supplement
clinical findings with respect to tumor size and extent, in all stages.
• ¶ The involvement of vascular/lymphatic spaces does not change the
staging. The lateral extent of the lesion is no longer considered.
• Δ Adding notation of r (imaging) and p (pathology) to indicate the findings
that are used to allocate the case to Stage IIIC. Example: If imaging
indicates pelvic lymph node metastasis, the stage allocation would be
Stage IIIC1r, and if confirmed by pathologic findings, it would be Stage
IIIC1p. The type of imaging modality or pathology technique used should
always be documented.

7. Early vs locally advanced
Following staging, locally advanced cervical cancer is defined by the presence
of any of the following findings -
• Confined to the cervix with a clinically visible tumor >4 cm (stage IB3)
●Invades beyond uterus but not to pelvic wall or to lower third of vagina (stage
II)
●Extends to the pelvic sidewall and/or involves the lower third of vagina, and/or
causes hydronephrosis or a nonfunctioning kidney (stage III)
●Invades the mucosa of the bladder or rectum, or extends beyond the true
pelvis (stage IVA)

8. Approach to Treatment
• Stage IA1 – Cone biopsy or extrafascial hysterectomy without
lymphadenectomy. If intermediate- or high-risk factors are present, a
modified radical hysterectomy should be performed .
• Stage IA2 and IB1 - Modified radical hysterectomy with pelvic
lymphadenectomy.
• Stage IB2 - Radical hysterectomy with pelvic lymphadenectomy.

10. Extrafascial hysterectomy or conization
• Treatment with cervical conization or extrafascial hysterectomy is limited to
women with microinvasive disease with stromal invasion ≤3 mm in depth
(stage IA1) who have no evidence of intermediate- or high-risk features.
Conization is often performed as part of the diagnostic evaluation and
staging procedure for cervical cancer. Repeat conization is required if there
is a positive margin. Extrafascial hysterectomy, also referred to as simple
hysterectomy, involves removal of the uterus and cervix, but not the
parametria or more than the upper margin of the vagina. Vaginal
hysterectomy is the preferred approach. Given that patients who are
candidates for these procedures by definition are at low risk for lymph node
involvement, pelvic lymphadenectomy is not indicated.
• Extrafascial hysterectomy may be reasonable in patients with stage IA2
disease but is not recommended for women with stage IB1 disease.

13. Adjuvant chemoradiation is indicated for patients with the following:
●Intermediate-risk factors (ie, tumor size >4 cm, the presence of
lymphovascular space invasion [LVSI] and/or deep cervical stromal invasion),
or
●High-risk factors (ie, pathologically involved lymph nodes, parametrial
invasion, or positive surgical margins)

17. Surgery vs primary RT
• An important factor in the decision between surgery and RT is that ovarian
conservation is possible with surgery, thus avoiding premature menopause
and allowing more fertility options in reproductive-age patients. In addition,
RT is associated with more long-term sexual dysfunction than surgery .
• Based on the available data and other factors, for women with stage IA2,
IB1, and IB2 cervical cancer, we suggest surgery rather than primary RT.
For this patient population, we reserve primary RT with or without
chemotherapy for women who are not candidates for primary surgery due
to medical comorbidities or poor functional status. An exception is stage
IA1 cancer, which may be treated with more conservative surgery.

18. Surgical management

21. Surgery:
• Ovarian metastases are less common with squamous cell histology than adenocarcinoma
(0.8 versus 5 percent in one series ; thus, ovaries are typically preserved in women with
squamous histology and more commonly removed in those with adenocarcinoma.b
●The standard treatment for stage IA2 and stage IB1 cervical cancers is a modified radical
hysterectomy (class II hysterectomy)
●Patients with stage IB2 cervical cancers will typically undergo a radical hysterectomy (class
III hysterectomy) that includes removal of more vaginal tissue (up to the upper one-half) and
parametrial tissue, in addition to a lymph node assessment. The additional resection of
tissue, as compared with a modified radical hysterectomy, is performed in these patients
given the overall poor prognosis with stage IB2 disease

22. Mode of surgery
• For women undergoing radical hysterectomy for cervical cancer with
tumors >2 cm in diameter, we recommend laparotomy rather than
minimally invasive surgery (MIS [conventional laparoscopy or robotic-
assisted laparoscopy]). However, patients with smaller tumors (≤2 cm)
may be candidates for robotic-assisted surgery with appropriate counseling
of the risks and benefits associated with MIS.

24. Primary RT
• When indicated, computed tomography-
based planning should be used to
adequately visualize the cervix, rectum,
bladder, small bowel, and nodal stations.
• The inferior border should give a minimum
margin of 3 to 4 cm from the tumor, which
can be aided by the placement of a marker
at the time of simulation.
• A marker can also be placed clinically in
the cervix or if there is vaginal extent, at
the most distal edge of the tumor. This will
help ensure adequate coverage.

25. • The presence of distal vaginal disease into the lower one-third of the
vagina places the inguinal lymph nodes at risk and they should be included
in the treatment field.
• Patients may be treated in prone or supine positions. For the prone
position, a "belly board" is used to displace small bowel superiorly from the
pelvis and reduce toxicity.

26. Adjuvant therapy indications

27. Intermediate-risk disease - GOG 263 (CTRT OVER RT ALONE)
Final pathologic criteria (sometimes referred to as Sedlis' criteria) used to define
women at intermediate risk include the following-
●Presence of LVSI plus deep one-third cervical stromal invasion and tumor of any
size
●Presence of LVSI plus middle one-third stromal invasion and tumor size >2 cm
●Presence of LVSI plus superficial one-third stromal invasion and tumor size >5 cm
●No LVSI but deep or middle one-third stromal invasion and tumor size >4 cm
The risks of recurrence and death in the presence of these factors are up to 30
percent following surgery alone .

29. High-risk disease —CTRT OVER RT ALONE IN GOG 109 trial ( cisplatin
alone over cisplatin + 5FU)
Women are considered to be at high risk if any of the following features
(sometimes referred to as Peters' criteria) are present at final pathologic
review-
●Positive surgical margins
●Pathologically confirmed involvement of the pelvic lymph nodes
●Microscopic involvement of the parametrium
For women with high-risk factors, the recurrence risk is approximately 40
percent and the risk of death is up to 50 percent following surgery alone

30. Sequential CTRT VS concurrent CTRT- STARS trial
• In the STARS trial, among 1048 women with stage IB to IIA cervical cancer with adverse
pathologic factors followed for a median of 56 months, the DFS for sequential
chemoradiation versus RT alone was 90 versus 82 percent (HR 0.65, 95% CI 0.44-
0.96), and the five-year risk of cancer death was 92 versus 88 percent, respectively (HR
0.58, 95% CI 0.35-0.95), after adjustment for lymph node involvement.
• Sequential RT also improved three-year DFS compared with concurrent chemoradiation
(95 versus 85 percent; HR 0.65, 95% CI 0.44-0.96).
• Improvements in DFS and cancer death risk observed with concurrent chemoradiation
versus RT were not statistically significant (DFS HR 0.79, 95% CI 0.56-1.12; OS HR
0.78, 95% CI 0.49-1.23). Although these results are promising, we await confirmatory
clinical trials prior to recommending this approach, and instead suggest concurrent
chemoradiation, given previous evidence of benefit in early-stage cervical cancer.

31. RTOG 0418
Radiation Therapy Oncology Group (RTOG) 0418 was a phase II trial
evaluating the use of IMRT in a multi-institutional setting. This study
demonstrated that IMRT is feasible to use in multiple institutions with a
detailed protocol and attention to quality assurance.

32. TIME C TRIAL
In a phase III trial of IMRT versus standard therapy for the postoperative
treatment of cervical or endometrial carcinoma (TIME-C trial), among 278
patients randomly assigned to either traditional four-field pelvic irradiation or
IMRT, IMRT decreased gastrointestinal and urinary toxicity, with a trend for
an improvement in quality-of-life scores.

33. Radiotherapy technique

34. • RT technique — Adjuvant pelvic radiation therapy (RT) targets
the at-risk tissues in the pelvis to eradicate potential occult sites
of disease.
• Traditionally, treatment has been delivered using a four-field
technique, which employs equally weighted anteroposterior-
posteroanterior (AP-PA) and opposed lateral beams.
• With the use of 3D imaging, 3D conformal RT plans should be
designed to adequately cover soft tissue regions at risk, including
nearby parametrial and vaginal tissue and the pelvic lymph
nodes. It is important to take into account variations in patient
anatomy and postsurgical changes.

35. • It is necessary to adequately cover all locoregionally draining lymphatics, which include
obturator, internal iliac, presacral, external iliac, and common iliac lymph nodes (and para-
aortics if at sufficient risk for disease) through the vessel coalescence at the inferior vena cava,
which roughly corresponds to a superior field border at the L4-L5 disk space.
• Inferiorly, the field edge should extend 3 to 4 cm below the lowest extent of disease or to the
bottom of the obturator foramen.
• The lateral margin should be set 1.5 to 2 cm lateral to the pelvic brim or at the lateral edge of
the planned target volume contours and is designed to give a margin on the pelvic vessels and
lymphatics

36. Locally advanced cervical
cancer

37. OUTBACK trial- June 2021
• Adjuvant chemotherapy following chemoradiation as primary treatment for
locally advanced cervical cancer compared to chemoradiation alone: The
randomized phase III OUTBACK trial (ANZGOG 0902, RTOG 1174, NRG
0274).- JUNE 2021
• No benefit for adjuvant chemotherapy following chemoradiation for locally
advanced cervical cancer (June 2021)
• Standard treatment for locally advanced cervical cancer is concurrent
chemoradiation, but further treatment is being investigated to improve
outcomes. In a randomized trial including over 900 patients with locally
advanced cervical cancer, those assigned to standard cisplatin-based
chemoradiation, followed by four cycles of adjuvant carboplatin and paclitaxel,
experienced similar five-year overall survival as those assigned to concurrent
chemoradiation only (72 versus 71 percent. We continue to suggest concurrent
chemoradiation alone for patients with locally advanced cervical cancer.

38. Surveillance

42. Thank you