RAMB Novembro/Dezembro 2015

adalla

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ssoc

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2015; 61(6):536-542

tion included in the study, 75% had received prior treat-

ment with cisplatin for recurrent disease. The use of

bevacizumab led to improved overall response, progres-

sion-free time and survival.

44-46

There was benefit for patients with recurrent disease

in previously irradiated areas. Adverse effects included neu-

tropenia, hypertension (grade 3), gastrointestinal fistula,

and thromboembolism. However, the use of targeted ther-

apy allowed an improvement in overall survival compared

to chemotherapy alone. Other agents with anti angiogen-

ic activity that proved useful in the treatment of other ma-

lignancies are being investigated for cervical cancer, such

as sunitinib, pazopanib, lapatinib and cediranib.

The goal of immune therapy in cervical cancer is to

modify the patient’s immune response leading to the

elimination of cancer cells. One approach explores the

relationship of this malignancy with the human papillo-

ma virus (HPV). An Indian study of a vaccine with HPV-

-induced E7 protein, together with attenuated bacterium

(

Listeria monocytogenes

) as a vector, in over 100 women with

refractory or recurrent cervical cancer

showed promis-

ing results. After six months, 63% of patients were alive

and 12 patients had partial or complete response.

An-

other approach is the induction of regulatory cytotoxic

T lymphocyte-associated molecule 4 (CTLA-4), which is

important for activation of cellular immune response.

Monoclonal antibody ipilimumab blocks CTLA-4 and

promotes antitumor immunity, generating effective im-

mune response against the tumor. This drug is in a phase

1 study (GOG 9929/NCT01711515).

Last, another pos-

sibility being studied for cervical cancer is that of the in-

hibitory receptor 1 of cell death (PD-1). When attached

to its ligand PD-L1, which is found on tumor cells and

leads to blockage of effective antitumor immune response,

antibodies to both proteins may restore effective immune

response.

pecial

situations

In this topic, we will discuss the treatment of patients

with involvement of para-aortic lymph nodes, the role of

para-aortic lymphadenectomy, and surgical indication in

local recurrences (pelvic).

The two most important prognostic factors in cervi-

cal cancer, in addition to staging, are tumor size and lymph

node involvement. Among the patients with locally ad-

vanced tumors (IIB or higher), 15-30% have para-aortic

lymph node involvement. Imaging studies CT, MRI or

positron emission computed tomography (PET-CT) have

high rates of false negatives.

48-50

PET-CT has better accu-

racy, but fails in about 10-20% of cases (false negatives in

para-aortic region). The objective of investigating lymph

nodes in this region would be to select cases for treatment

with para-aortic field. However, studies in which routine

para-aortic lymphadenectomy was performed in locally

advanced tumors showed worse prognosis of patients,

even with more aggressive adjuvant treatment, such as

extending the radiotherapy field to the para-aortic region.

Benefit with increased survival to justify a para-aortic

lymphadenectomy was observed in patients with nega-

tive PET-CT results, and with microscopic disease found

only in pathological examination of the para-aortic lymph

nodes.

51-53

Apparently, patients with the disease in para-

aortic lymph nodes represent a group in which even ra-

diotherapy applied directly to these lymph nodes associ-

ated with chemotherapy, or chemotherapy alone, is not

able to improve prognosis.

Pelvic recurrence is a failure event that compromises

the survival and quality of life of patients. In such cases,

surgical treatment of choice is pelvic exenteration, a pro-

cedure that is re-assessed whenever progress is achieved

in the areas of surgery, supportive therapy and imaging

evaluation. This surgery may be divided into anterior, pos-

terior or total. Anterior exenteration comprises the re-

moval of the recurrent tumor in addition to the bladder

compartment. Posterior exenteration refers to the remov-

al of the rectum in addition to the tumor. Last, total ex-

enteration includes the removal of both the bladder and

rectum. Another more recent classification divides sur-

gery into categories (supralevator, infralevator, and infra-

levator with vulvectomy) that are chosen based on the ex-

tent of the recurring disease.

54,55

Due to high rates of

complications and mortality associated with this surgery,

it should be reserved for much selected cases. It is espe-

cially suitable for pelvic recurrence after chemoradiation

and when the surgeon anticipates the possibility of ob-

taining surgical margin, a prerequisite for cure.

Selection criteria include centered relapse with neg-

ative lymph nodes and no visceral metastases.

54,55

As pre-

operative assessment, all the candidates for pelvic exen-

teration should undergo PET-CT to rule out distant

disease. PET-CT is the imaging study with greater accu-

racy to detect cervical cancer recurrences.

56-58

As the oc-

currence of positive lymph nodes is one of the most fre-

quent reasons to quit exenteration during surgery, prior

assessment of pelvic and para-aortic lymph nodes by lap-

aroscopy may be an alternative.

Successful exenteration depends on the following

preoperative prognostic factors: tumor size, time from

initial treatment to recurrence (disease-free survival) and

tumor histology. Tumor size greater than 5 cm, recur-