RAMB Novembro/Dezembro 2015

adalla

538

ssoc

ras

2015; 61(6):536-542

deep invasion of the cervical stroma.

The presence of

any of the major criteria, or a combination of the Sedlis

criteria, is an indication for adjuvant pelvic radiotherapy,

plus teletherapy associated with brachytherapy in cases

of worse prognosis. The addition of chemotherapy con-

current with radiation therapy (cisplatin in weekly dos-

es) for cases with higher risk of recurrence, especially for

patients with more than one positive lymph node, showed

benefits in terms of overall survival and recurrence-free

interval.

reatment

locally

advanced

cervical

tumors

Tumors at stage IB2, IIA 2, III and IV are included in this

category. For all these situations, the recommended treat-

ment since 1999 based on several multicenter randomized

trials is the combination of chemotherapy and radiation.

The regimen considered standard is IV administration of

cisplatin weekly (40 mg/m

) associated with radiotherapy

(5 sessions per week for six weeks).

For best results, the

treatment as outlined above should last between 50 and

55 days. This approach, compared with radiotherapy alone,

led to an overall survival benefit of 8%, 9% for local relapse-

free interval, and 7% in recurrence-free interval. However,

there is increased toxicity and even logistical problems that

prevent treatment as required in most of these cases. Ad-

juvant hysterectomy is a procedure still under debate. The

guidelines mention the procedure for situations where the

radiation cannot be completed (degree of recommenda-

tion 3).

However, response to radiotherapy is worse for

adenocarcinomas,

9,15,16

and a Brazilian study showed high

rates of residual tumor in the surgical specimens of pa-

tients who underwent surgery 3-4 weeks after completion

of treatment with radiotherapy and chemotherapy.

When

surgery is indicated, salpingo-oophorectomy should be in-

dicated along with hysterectomy

9,15,16

considering ovarian

failure caused by radiotherapy.

The limited results of chemoradiation for locally ad-

vanced tumors, especially related to small impact on re-

ducing recurrences at a distance, led to the search for new

strategies and the application of additional cycles of che-

motherapy after completion of the initial treatment.

The most studied drugs are cisplatin, combined or not

with gemcitabine,

18-22

and paclitaxel combined with car-

boplatin. Despite promising results, with improved sur-

vival and disease-free interval, there is substantial increase

in toxicity with additional cycles of chemotherapy. Cur-

rently, two international phase 3 studies are in progress.

The drugs studied are carboplatin and paclitaxel in four

cycles after chemoradiotherapy (ANZGOG 0902/ GOG

0274/NCT01414608 and Radiation Therapy Oncology

Group [RTOG] 0724/NCT00980954).

Another alterna-

tive for the treatment of locally advanced lesions is neo-

adjuvant chemotherapy followed by surgery in cases with

good response. Although not recommended as a stan-

dard therapy, this approach is employed in about 25% of

patients with locally advanced tumors. Although not in-

dicated in the guidelines as an alternative

non-random-

ized studies and meta-analyzes

show that this treatment

gives better results than radiotherapy alone.

The meta-

analyzes show a reduction of up to 35% in the risk of

death, and gain of 15% in survival after 5 years, compared

to the use of radiotherapy alone.

14,17

It is also observed re-

versal of intermediate and high risk indicators, such as

parametrial invasion, depth of cervical invasion and tu-

mor diameter.

The only randomized study comparing

this treatment alternative with chemo-sensitization is in

patient follow-up phase (EORTC55994/NCT00039338)

and its results will be presented in 2018.

ertility

preservation

To preserve fertility, conservative surgery (with preserva-

tion of uterine body) and ovarian transposition are dis-

cussed.

In patients without children and with initial tumors

of the cervix, radical trachelectomy is an alternative em-

ployed for some time. This surgery involves removing the

cervix, along with parametria, proximal third of the va-

gina and pelvic lymph nodes. The abdominal approach

allows better dissection of the parametria but the vaginal

route can be used by trained teams. For lymphadenecto-

my, laparoscopy is the preferred option. Trachelectomy

is considered a safe procedure if the following selection

criteria are used: usual histology (squamous cell carcino-

ma or adenocarcinoma, but not neuroendocrine tumors),

tumor size less than 2 cm (confirmed on physical exam-

ination and MRI of the pelvis), no disease beyond the cer-

vix (confirmed by CT, MRI or PET-CT), tumor-free pelvic

lymph nodes, and surgical specimen with free margins.

26-28

However, we know that the removal of parametria and

proximal third of the vagina affects the future obstetric

condition of the patient, with higher frequency of mis-

carriages and premature births. Thus, in view of the low

probability of parametrial involvement in patients with

stage IA2 and IB1 (tumor measuring up to 2 cm), coniza-

tion to obtain clear margins associated with pelvic lymph-

adenectomy has been studied without parametrectomy

and colpectomy in these situations.

3,4

Another approach

to IB1 tumors is the use of neoadjuvant chemotherapy

prior to trachelectomy.