Cervical Cancer Flashcards
Cervical Cancer
Pathogenesis
- Cervical cancer is causally related to infection with oncogenic human papillomavirus (HPV) strains.
- Cervical dysplasia is a precursor to cervical cancer
- Risk of progression to invasive CA increases w/ grade of dysplasia
Cervical Cancer
Histologies
- Squamous Cell: 72.1% - Highly associated with HPV
- Adenocarcinoma: 19% - HPV related. Associated with worse prognosis
- Adenosquamous: <5% - Mixed glandular/squamous features. Poor Prognosis
- Other Subtypes: Rare. Poor prognosis. Neuroendocrine, small cell, glassy cell, primary sarcoma
Cervical Cancer
Screening
Screening:
- Age 21-29: Cytology every 3 years
- Age 30-65: Cytology every 3 years, HPV every 5 years
- Age>65: No Screening Recommended
PAP Test: Effective Screening Tool
HPV DNA Testing
Frequency of testing may increase w/L
- abnormal PAP/HPV tests
- Immunodeficiency Syndrome (HIV, steroid use)
- Personal Hx of cervical cancer
Cervical Cancer
Screening
Human Papillomavirus 9-valent Vaccine, Recombinant against HPV strains 6, 11, 16, 18, 31, 33, 45, 52, 58 (Gardasil®)
- Approved for females aged 9-45
- Approved for males 9-45
Cervical Cancer
Primary Treatment
GOAL: Cure
- Early Stage - Cure very likely
- Advanced Stage - Less likely but goal
- Metastatic - Rarely Curable
Treatment includes - Surgery, Radiation, Chemotherapy
Cervical Cancer
Primary Treatment
Surgery
- Extent of surgery varies with stage of disease (I-IIA) and desire for fertility
-
Fertility-Sparing approaces may be considered for select pts
- Fertility sparing approaches include cone biopsy or radical vaginal trachelectomy with laparoscopic lymphadenectomy
-
Non-Fertility Sparing
- Simple/extrafascia hyserectomy (Type A)
- Modified Radical Hysterectomy (Type B)
- Radical hysterectomy (Type C)
-
Pelvic Lymph Node Disssection w/ or w/o para-aortic lymph node sampling
- Usually accomopanies the surgery of choice above
Cervical Cancer
Primary Treatment
Radiation
- Therapies include pelvic external beam radiation therapy (EBRT) and vaginal brachytherapy, along with sterotactic body radiotherapy which is applied to isolated metastases
The combination of EBRT and brachytherapy are the mainstay of primary treatment for advanced stage disease (stage IIB-IVA).
Radiation can also be used following surgery to reduce the risk of recurrence in patients with high-risk features (adjuvant therapy)
Cervical Cancer
Primary Treatment
Chemotherapy
ROLE in THERAPY
- Chemotherapy plays LIMITED role in management of cervical cancer
- Most commonly used in conjunction with radiation to enhance its effectiveness (CHEMOSENSITIZATION)
- Cisplatin most commonly used for this purpose
- Platinum-based combination chemotherapy is used in the management of advanced stage (IVB) or recurrent cervical cancer.
- The number of active agents used in the treatment of metastatic disease is limited.
Cervical Cancer
Treatment
CIN-III (Carcinoma in situ: High-grade dysplasia)
(Stage 0)
CIN-III (Carcinoma in situ; high-grade dysplasia)
- Patients with persistent high-grade intra-epithelial neoplasia (Stage 0) are at higher risk of developing invasive cervical cancer.
- Persistent CIN-III can be treated with either excision or ablation procedures.
- Excision procedures include a CKC (cold knife cone) or LEEP (loop electrosurgical excision procedure) to negative margins or a total hysterectomy.
- Ablative procedures include cryotherapy or laser ablation.
- Excessive use of ablative cervical procedures is associated with a higher risk of miscarriage.
Cervical Cancer
Treatment
Early Stage Disease
(Stage I-IIA)
Early Stage Disease (Stage I-IIA)
Treatment can vary based on staging and fertility concerns
- combination of surgery, chemotherapy, brachytherapy
Fertility presevation may be considered for subset of patients, including stage IA1, IA2, IB1, and IB2
Cervical Cancer
Treatment
Advanced Stage Disease
(Bulky Stage IIB, III and IVA)
Advanced Stage Disease (Bulky Stage IIB, III and IVA)
- Surgery no longer plays primary role in the treatment of advanced stage disease
- Primary treatment focused on RADIATION
Local/Regional Recurrence after prior XRT or stage IVB mtx disease
- systemic tx or best supportive care
Chemosentization
- Platinum-containing chemotherapy improves response rate
Cervical Cancer
Treatment
Clinical Issues XRT + Chemosensitization
Clinical issues related to XRT plus chmosensitization
- survival related to dose intensity of XRT (complete tx w/i 8 weeks)
- CDDP given in 5-6 doses
CDDP 40mg/m2 weekly for 5-6 weeks (STANDARD TX)
- Cap dose at 70mg
Pain Assessment:
- If patients present w/ pain, pain will transiently increase during fisr 1-2 weeks of XRT due to inflammatory response
Weight loss
- may occur with Pelvic XRT
Cervical Cancer
Treatment
Treatment of Relapsed Disease
Defined as appearance of new lesion after achieving complete response to primary therapy
Locoregional therapy: retreatment for localized recurrence
- Radiation therapy and/or chemotherapy
- Surgery
Locoregional recurrence without prior radiation therapy or relapse outside previous radiation field
- Tumor directed EBRT with or without chemotherapy and/or brachytherapy; surgical resection can be considered
- Consider alternative non-cisplatin containing chemotherapy for patients who relapse soon after completing initial chemoradiation
Central pelvic recurrence after prior radiation therapy
- Pelvic exenteration may be performed in highly selected patients with persistent or recurrent cervical cancer confined to the central pelvis following radiation therapy. This offers the potential for long-term cure, although few patients qualify based on pattern of recurrence.
- Radical hysterectomy or brachytherapy may be an option in patients with small lesions (<2 cm)
Cervical Cancer
Treatment
Primary Treatment of Stage IVB Disease
The most common distant metastatic sites are the lungs, mediastinal and supraclavicular lymph nodes, bones, and liver
Palliative Care is most common approach
Platinum-containing doublets (combination chemotherapy) - standard if patient alread received CDDP as a radiation sensitizer
- Carboplatin-based doublets (CATEGORY 1) in patients who have received prior CDDP therapy
Addition of Bevacizumab to Platinum-based doublet chemotherapy has been show to improve overall survival in primary advanced or recurrent cervical cancer
Cervical Cancer
Treatment
Recurrent/Metastatic Cervical Cancer
Single Agent Therapy
Pembrolizumab
For recurrent/metastatic cervical cancer, pembrolizumab may be considered in patients who express:
- PDL-1
- CPS >= 1
- Disease progression after chemotherapy
200mg q3 weeks
