Cancer of the Cervix: Current Management and New Approaches: Review 2

Despite the fact that cervica cancer represents only a small portion of cancers in the United States, it is the second most common cancer in the world. Great strides in improving patient outcomes for this disease have been made in the past decade. The authors have presented a well organized and comprehensive review of the current management of carcinoma of the cervix.

Chemoradiation

The authors review the studies that prompted the National Cancer Institute (NCI) to issue an alert stating that "Strong consideration should be given to the incorporation of concurrent chemotherapy with radiation in women who require radiation therapy for the treatment of cervical cancer."[1] Despite this recommendation, many questions remain-for example, what is the optimal chemotherapy regimen, and how is chemotherapy appropriately integrated with external-beam and brachytherapy treatments. Cisplatin was used in all the studies that formed the basis of the NCI alert, but some studies combined cisplatin with other agents (fluorouracil and hydroxyurea).

As pointed out in this review article, the National Cancer Institute of Canada trial did not show any benefit to adding chemotherapy to radiation.[2] Shivnani et al incorrectly attribute this to the delivery of radiotherapy over a shorter time period. As they later note, overall treatment time has been shown to be a critical determinant of outcome following definitive radiotherapy. One series showed a decrement in local control of 0.85% per day for treatments extending beyond 49 days.[3] The Canadian authors feel that concurrent chemotherapy may not add incremental benefit to optimally delivered radiotherapy. The median overall treatment time in US trials was 62 to 65 days compared with 50 to 55 days in the Canadian study. Based on the US studies and NCI consensus statement, there appears to be no doubt that cisplatin concurrent with radiation is currently the standard of care in the United States.

Hopefully, questions about the optimal chemotherapy regimen and timing of delivery during radiation therapy will be answered by future trials. These trials must be performed with optimally delivered radiation using adequate doses and fields, and minimizing overall treatment times.

Radiotherapy Techniques

This section of the article by Shivnani et al provides an excellent comprehensive review of radiotherapeutic management, including external-beam treatment and brachytherapy. The authors give detailed descriptions of both low- and high-dose-rate (LDR and HDR) brachytherapy, including the advantages and disadvantages of both approaches. As noted, there have been a variety of fractionation schemes used for HDR treatment. After careful analysis, the Gynecology Oncology Group has adopted 30 Gy in five fractions for their protocols. Several single-institution studies as well as a few randomized trials done outside the United States have shown equivalency of HDR to LDR brachytherapy in terms of tumor control and complications with fraction sizes of 7 Gy or less.[4]

Positron-Emission Tomography

The section on positron-emission tomography (PET) is perhaps the most intriguing part of the review article. As the authors point out, this new imaging modality may provide a more accurate assessment of the extent of disease and perhaps gauge response more accurately. The ability to detect involved nodes at a smaller size may allow radiation oncologists to design more appropriate fields and perhaps provide dose escalation to the site of an involved lymph node.

Unlike the primary tumor, which is treated to a high dose with the addition of brachytherapy to external-beam treatment, the nodal regions are more difficult to treat adequately with external-beam treatment alone. This is an excellent opportunity to combine PET imaging with intensity-modulated radiotherapy (IMRT) to achieve dose escalation. The authors discuss the use of IMRT as a technique to decrease treatment morbidity. It may also provide a mechanism for encompassing the paraaortic nodes in addition to the pelvic lymph nodes, which are classically treated in the standard external-beam fields with concurrent chemotherapy.[5] The IMRT treatment in conjunction with image guidance, may allow for the delivery of a more tumoricidal dose to an involved lymph node.

As the authors note, another approach to providing more comprehensive nodal treatment has been to add a thiol-containing compound (amifostine [Ethyol]), which can protect against both radiation- and chemotherapy-induced toxicity when fields are extended to cover more nodal groups. A trial of this radioprotector is being undertaken by the Radiation Therapy Oncology Group.

Conclusions

The article by Shivnani et al provides an excellent review of current approaches to definitive treatment of carcinoma of the cervix. The authors have also described some promising areas of current research. Potential improvements in the assessment of disease extent and treatment responses with the use of better imaging modalities are well described. New approaches to decreasing treatment toxicity are also nicely reviewed by the authors. Hopefully, these new technologies will lead to improved outcomes in patients with this common form of cancer.

-Kristina Gerszten, MD

References:

1. National Cancer Institute. Concurrent chemoradiotherapy for cervical cancer. Clinical announcement. Washington, DC, February 22, 1999.

2. Pearcey R, Brundage M, Drouin P, et al: Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix. J Clin Oncol 20:966-972, 2002.

3. Perez, CA, Grigsby PW, Castro-Vita H, et al: Carcinoma of the uterine cervix, I. Impact of prolongation of overall treatment time and timing of brachytherapy on outcome of radiation therapy. Int J Radiat Oncol Biol Phys 32:1275-1288, 1995.

4. Gerszten K, Gooding W, Lin Y, et al: A single institutional experience with definitve radiotherapy for cervical cancer using both high and low-dose rate brachytherapy. Gynecologic Oncol 102:500-507, 2006.

5. Gerszten K, Colonello K, Heron D, et al: Feasibility of concurrent cisplatin and extended field radiation therapy (EFRT) using intensity modulated radiotherapy for carcinoma of the cervix. Gynecologic Oncol 102:182-188, 2006.