Radiotherapy usage rates exhibit wide variations both within and between countries. Current estimates of the proportion of cancer patients who should optimally receive radiotherapy are based either on expert opinion or on the measurement of actual usage rates rather than on the best available scientific evidence.
With the goal of developing an evidence-based benchmark for radiotherapy use in the treatment of malignancies of the cervix, vagina, vulva, and ovary (endometrial malignancies are covered in a separate article), the authors reviewed international evidence-based treatment guidelines. Optimal radiotherapy usage trees were constructed, and proportions of patients with clinical indications for radiotherapy were obtained from epidemiologic data. These ideal usage rates were compared with actual radiotherapy utilization rates recorded in Australia and elsewhere.
According to the best available evidence, radiotherapy is indicated at least once for 58% of patients with cervical carcinoma, 4% of patients with ovarian carcinoma, 100% of patients with vaginal carcinoma, and 34% of patients with vulvar carcinoma. A review of the limited data available suggests that actual radiotherapy usage rates for patients with gynecologic malignancies are comparable to optimal usage rates.
Radiotherapy is an essential method of cancer treatment, contributing to cure or palliation for many patients. Nonetheless, there is considerable variation, both within and among nations, in terms of the proportion of patients with malignant disease who receive radiotherapy.
Radiotherapy facilities have high initial capital costs, and their operation is staff intensive. One of the benchmarks of the adequacy of radiotherapy provision is the usage rate—that is, the proportion of patients with new diagnoses of cancer who receive at least one course of radiotherapy during the course of their illness. The planning of efficient and equitable radiotherapy services for a population requires estimation of optimal radiotherapy usage rates for all patients with cancer. In the current report, we provide an estimate of the optimal usage rate specifically for patients with gynecologic malignancies.
Tyldesley et al.1 described an evidence-based approach for determining optimal rates of radiotherapy use in the management of lung carcinoma, and our group has also calculated optimal rates of radiotherapy use in this setting using similar methods and considering Australian data and treatment guidelines.2 In addition, optimal radiotherapy usage rates have been reported for patients with breast carcinoma,3, 4 melanoma,5 colorectal carcinoma,6 and prostate carcinoma.7 The current study builds on previous approaches by using guideline-based evidence and recent epidemiologic data to estimate the optimal percentages of patients with malignancies of the cervix, vulva, vagina, and ovary who should, according to the best available evidence, receive at least one course of radiotherapy during the course of their illness. These ideal usage rates are then compared with corresponding rates recorded in actual clinical practice. The current approach also provides a useful template for predicting the impact of future changes (e.g., in the incidence of gynecologic malignancies, in disease stage at presentation, and in indications for radiotherapy) on radiotherapy usage rates.
MATERIALS AND METHODS
Development of a Model Describing Optimal Radiotherapy Use
Indications for radiotherapy
An indication for radiotherapy is defined as a clinical situation in which radiotherapy is considered the treatment of choice on the basis of evidence suggesting that such treatment will result in a more favorable clinical outcome than will any other type of treatment (including no treatment) and in which the patient is an appropriate candidate for radiotherapy in terms of performance status indicators and the presence or absence of comorbidities. The superiority of radiotherapy over other treatment options could be established on the basis of survival, local control, or toxicity outcomes.
National-level guidelines and evidence-based recommendations issued by major institutions regarding the treatment of gynecologic malignancies were identified. These included the National Cancer Institute PDQ guidelines for cervical, vulvar, vaginal, and ovarian malignancies8–11; the National Institutes of Health consensus statement regarding cervical carcinoma12; treatment guidelines issued by the Federation Internationale de Gynecologie et d'Obstetrique (FIGO) Committee for the Management of Cervical and Endometrial Cancer13; the British Columbia Cancer Agency's treatment guidelines for cervical, vulvar, vaginal, and ovarian malignancies14–17; and the National Comprehensive Cancer Network's treatment guidelines for cervical and ovarian malignancies.18, 19 Treatments documented in peer-reviewed journals were used as a basis for developing indications for radiotherapy in instances in which published guidelines were not specific. Based on the recommendations that were established by reviewing published guidelines and documented treatment methods, a list of indications for radiotherapy in the treatment of gynecologic malignancies was created (Table 1). The evidence in support of each recommendation for radiotherapy was classified according to the Australian National Health and Medical Research Council's hierarchy of levels of evidence.20
Table 1. Indications for Radiotherapy: Levels and Sources of Evidence
Proportion of all patients with the malignancy in question
Level I: systematic review of all relevant randomized studies; Level II: at least 1 properly conducted randomized trial; Level III: well-designed controlled trials without randomization, includes trials with “pseudo-randomization” or comparative studies; Level IV: case series. Adapted from National Health and Medical Reearch Council. Guide to the development, implementation and evaluation of clinical practice guidelines, appendix B. 1998:56.
PS: performance status; RT: radiotherapy; NIH: National Institutes of Health; FIGO: Federation Internationale de Gynecologie et d'Obstetrique; NCCN: National Comprehensive Cancer Network; GOG: Gynecologic Oncology Group; CNS: central nervous system.
Good PS, nonbulky Stage IB–IIA disease, surgery, positive lymph nodes
National Cancer Institute PDQ statement8; NIH consensus statement12; FIGO guidelines13; BC Cancer Agency guidelines14; NCCN guidelines18
Nonbulky Stage IB–IIA disease, good PS, surgery, negative lymph nodes, close or positive margins
National Cancer Institute PDQ statement8; NIH consensus statement12; FIGO guidelines13; BC Cancer Agency guidelines14; NCCN guidelines18
Nonbulky Stage IB–IIA disease, good PS, surgery, negative lymph nodes, negative margins, high risk of local failure (GOG score > 120)
National Cancer Institute PDQ statement8; NCCN guidelines18
Nonbulky Stage IB–IIA disease, good PS, surgery, no lymph nodes, negative margins, low risk of local failure (GOG score < 120), local recurrence
National Cancer Institute PDQ statement9; Berek and Hacker34; Homesley et al.35
Total proportion for whom radiotherapy is recommended
RT alone or RT + surgery or chemotherapy
National Cancer Institute PDQ statement10; BC Cancer Agency guidelines17
Total proportion for whom radiotherapy is recommended
Indications for radiotherapy may arise in the initial stages of treatment, or they may be delayed (e.g., for patients who develop local or distant recurrences and who have not previously required radiotherapy). Patients requiring radiotherapy were counted only once, even if they had indications for radiotherapy at multiple points during the course of their illness. This method of counting allowed comparison of the optimal usage rate with the actual usage rate (defined [for each type of malignancy] as the number of patients receiving radiotherapy for the first time divided by the incidence of the malignancy in question during a given period). The current study dealt only with the use of external-beam radiotherapy, as the results were intended to be of assistance in determining the number of linear accelerators required to meet the needs of a given population. Thus, brachytherapy use was not investigated.
We used epidemiologic data to calculate the percentages of patients with cervical, vulval ovarian and vaginal cancer who had clinical attributes amounting to an indication for radiotherapy. The relative quality of the epidemiologic data was ranked using the hierarchy described in Table 2. The data source with the highest quality ranking was used to determine the incidence of each indication for radiotherapy. Australian epidemiologic data were used whenever possible, because the results of the current study will be used in planning the development of radiotherapy facilities in Australia.
Table 2. Incidence of Attributes Associated with Indications for Radiotherapy
Characteristic(s) defining population or subpopulation of interest
Quality of information/hierarchy for epidemiological data: α-Australian National Epidemiological data; β-Australian State Cancer Registry; γ-Epidemiological databases from other large international groups (eg. SEER); δ-Results from reports of a random sample from a population; ϵ-Comprehensive multi-institutional database; ζ-Comprehensive single-institutional database; θ-Multi-institutional reports on selected groups (eg. multi-institutional clinical trials); λ-Single-institutional reports on selected groups of cases.
Epidemiologic data were obtained from national databases21 or from national surveys of representative samples of Australian patients with malignant disease. When national data were unavailable, more specific sources (such as state cancer registries) were sought out for information regarding tumor stage and pathology. A key source of data for the current study was the South Australian Network of Hospital-Based Cancer Registries (SAH-BCR).22 The registries that participate in this network are overseen by major teaching hospitals and include data on patients attending the five largest cancer centers in South Australia. (Taken together, these centers manage over half of all cancer cases in South Australia.) The SAH-BCR database includes information on disease stage that is not available in other Australian state databases. Institutional data reported in published articles were used when higher-level epidemiologic data could not be obtained.
Radiotherapy utilization tree
Based on established indications for radiotherapy in the treatment of gynecologic cancer and on existing epidemiologic data, a radiotherapy usage tree was generated for each gynecologic malignancy (Fig. 1) using TreeAge Data software (Version 3.5; TreeAge Software, Williamstown, MA). On the decision tree, each branch point represents an attribute (e.g., tumor stage or the presence/absence of clear surgical margins) that affects a clinical management decision. Above each branch on the tree is a description of the specific attributes that led to a given treatment decision; each number listed below the branch represents the proportion of patients with a given attribute according to epidemiologic data. Each terminal branch indicated whether radiotherapy was recommended for individuals who had a specified set of clinical attributes.
Radiotherapy usage trees and descriptions of data sources were sent to a multidisciplinary panel of experts on gynecologic malignancy (from surgical, medical oncology, radiation oncology, palliative care, and nursing backgrounds) for external review. Reviewers were asked to comment on the appropriateness of the recommendations and on the epidemiologic data that were used, and changes were made on the basis of their feedback. The review process was overseen by an independent steering committee of general oncology experts convened by the Australian National Cancer Control Initiative.
Optimal Radiotherapy Utilization Rate
Radiotherapy usage trees for patients with cervical, ovarian, vulvar, and vaginal malignancies are shown in Figure 1. Table 1 summarizes each group of clinical attributes associated with an indication for radiotherapy, as well as the guidelines or sources of evidence on which the indication was based. The rightmost column of the table lists the proportions of patients who possess a given set of attributes according to disease type. Summing the entries in this column yields an optimal radiotherapy usage rate for each type of gynecologic malignancy (58% for cervical carcinoma, 4% for ovarian carcinoma, 100% for vaginal carcinoma, and 34% for vulvar carcinoma).
With regard to cervical carcinoma, radiotherapy is indicated for patients with Stage IB–IIA disease who have poor performance status and for patients with Stage IIB–IVA disease as definitive treatment (usually with concurrent chemotherapy). Postoperative radiotherapy is recommended for patients with positive pelvic lymph nodes, positive surgical margins, or other adverse pathologic features. Radiotherapy also is recommended as a palliative measure for local symptoms such as pain, bleeding, and symptoms secondary to bone or lymph node metastases in patients with Stage IVB cervical carcinoma. Furthermore, palliative radiotherapy is recommended for patients with any stage of disease when poor performance status precludes another treatment option (e.g., surgery), for patients with advanced disease accompanied by local primary symptoms or symptoms related to bone metastases, and for patients with recurrent disease following surgery.
According to published guidelines, surgery is the mainstay of treatment for patients with vulvar carcinoma. Radiotherapy is recommended for patients with an intermediate or high risk of locoregional recurrence following surgery and for patients who develop lymph node recurrence following surgery.
The National Cancer Institute's guidelines for the management of vaginal cancer10 recommend radiotherapy (either alone or in conjunction with chemotherapy and/or surgery) for the treatment of all stages of disease. Therefore, our optimal usage tree indicates that all patients with vaginal cancer should receive radiotherapy (adjuvant, radical, or palliative).
Indications for radiotherapy in the treatment of ovarian carcinoma are uncommon. The optimal usage tree recommends radiotherapy only for patients with symptomatic brain, bone, or lymph node metastases. There may be other situations in which radiotherapy is indicated (e.g., for patients with advanced-stage disease who experience progression following systemic therapy and develop uncontrolled pelvic symptoms, for patients for whom systemic therapy is not indicated, etc.); however, such indications are present in only a very small percentage of all ovarian carcinoma cases, and therefore, they have not been included in our tree. The optimal usage tree indicates that 38% of all patients with ovarian carcinoma ultimately develop metastatic disease (either at diagnosis or following treatment), which occurs at sites associated with an indication for radiotherapy in 11% of these cases.23
Table 2 presents epidemiologic data corresponding to each branch point on our optimal usage trees, along with information on data sources and hierarchic levels of data quality. For instances in which there were several published reports of equal quality, data are presented together with their sources. Sensitivity analysis was performed when data sources of similar quality yielded results that varied by > 10%.
Cervical carcinoma was staged according to the FIGO system, because this system was used in most of the works reviewed in the current study. Epidemiologic data regarding the stage-specific incidence of cervical carcinoma were obtained from the National Cancer Institute Surveillance, Epidemiology, and End Results database rather than from Australian sources, because Australian state cancer registries did not report disease substages.
We calculated optimal radiotherapy usage rates for each gynecologic malignancy by determining the frequency of each indication for radiotherapy and then summing these individual frequencies to obtain a total optimal usage rate. The optimal usage rate was then compared with current usage data obtained from studies investigating patterns of care.
Comparison of Optimal Use with Actual Practice
A literature review of patterns-of-care studies revealed that only a limited number of studies have assessed actual rates of radiotherapy use for patients with gynecologic malignancies. One Australian study of patients with ovarian cancer reported a radiotherapy usage rate of 2%.24 Aside from that study, we used published data from the SEER database,25 the American College of Surgeons database,26 and the SAH-BCR22 to calculate actual rates of radiotherapy use for each type of gynecologic malignancy. The latter two sources carry potential biases in that they are hospital-based registries and therefore do not necessarily include all cases (e.g, cases managed conservatively and cases managed outside the hospital setting). Older patients and patients with poor performance status also may be less likely to be included in such hospital-based databases.
Tables 3–5 present actual radiotherapy usage rates for patients with cervical, ovarian, and vulvar malignancies. There were large discrepancies between optimal and actual radiotherapy usage rates in the treatment of vaginal carcinoma and vulvar carcinoma. Overall usage rates for the period 1984–1998 in South Australia were higher than the corresponding rates reported by SEER and by the American College of Surgeons. There were only 44 cases of vaginal carcinoma and 174 cases of vulvar carcinoma included in the SAHBCR report. These account for approximately half of all cases that occurred in South Australia during that time period; thus, selection biases may have distorted our findings.
Table 3. Optimal and Actual Radiotherapy Use in the Treatment of Cervical Malignancies
ACS: American College of Surgeons; SEER: National Cancer Institute Surveillance, Epidemiology, and End Results Program; N.A.: not available.
Percentage of all patients with the specified stage of disease.
No. of patients
Patients eligible to receive or receiving radiotherapy (%a)
In South Australia, there was a significant decrease in radiotherapy usage rates for patients with cervical carcinoma between the period 1984–1991 and the period 1992–1998. This finding may be explained by a shift toward earlier presentation of cervical carcinoma as a result of cervical screening programs. Rates of radiotherapy use in the treatment of vaginal and vulvar malignancies were reported together and did not change over time. According to both the SEER database and the American College of Surgeons database, radiotherapy usage did not change substantially between 1996 and 1999 for patients with any type of gynecologic malignancy.
Figures 2 and 3 show age-specific usage rates for patients with cervical, vaginal, and vulvar malignancies. Radiotherapy use among patients with cervical carcinoma increased with increasing age in all three reports. In the combined South Australian analysis of vaginal and vulvar malignancies, the radiotherapy usage rate decreased significantly with increasing age, from 48% for patients age < 55 years to 22% for patients age > 75 years (P = 0.009). In contrast, the SEER database indicated that radiotherapy use increased with increasing age for patients with vulvar malignancies as well as patients with vaginal malignancies.
In the current study, we determined that according to evidence-based guidelines, the optimal rates of radiotherapy use in the treatment of gynecologic malignancies were as follows: 58% for cervical carcinoma, 4% for ovarian carcinoma, 100% for vaginal carcinoma, and 34% for vulvar carcinoma. We also demonstrated the feasibility of generating benchmarks based on guideline recommendations that can easily be adjusted to account for temporal and geographic variations in incidence and that can be useful in determining the ideal allocation of radiotherapy resources.
There was one major controversy with respect to the treatment of gynecologic malignancies that warrants further discussion. The National Cancer Institute PDQ guidelines and the National Institutes of Health consensus statement both state that radiotherapy and surgery are equally efficacious for patients with Stage IB–IIA cervical carcinoma and that both options should therefore be presented to such patients. Because there is no evidence indicating the superiority of either treatment modality in this setting, actual usage rates were used in the analysis. In Australia, the vast majority of patients with early-stage cervical carcinoma are treated with radical gynecologic surgery. Exceptions typically include patients with poor performance status, patients with significant comorbidity, and patients who choose not to undergo surgery. The decision tree therefore depicts surgery as the primary treatment option for all patients with Stage IB–IIA disease and favorable performance status, with radical radiotherapy being considered the definitive treatment option only for patients with poor performance status (i.e., Eastern Cooperative Oncology Group performance status 4). Postoperative radiotherapy is indicated when positive pelvic lymph nodes, positive surgical margins, or other risk factors (e.g., increased clinical tumor size, increased depth of invasion, lymphovascular invasion, etc.) are present. The remaining treatment recommendations were consistent across all sets of guidelines.
The calculated optimal usage rate for patients with cervical carcinoma was similar to the rate observed in actual practice. In contrast, the optimal usage rate for patients with vulvar carcinoma was approximately three times greater than the observed rate, possibly because patients with vulvar carcinoma tend to be significantly older than patients with other types of gynecologic malignancies and therefore may not be offered radiotherapy by their physicians.
A patterns-of-care study conducted in the Australian state of Victoria reported an actual radiotherapy usage rate of 2% for patients diagnosed with ovarian carcinoma between 1993 and 199524; in contrast, we calculated an optimal rate of 4% for patients with this malignancy. The Victorian study did not provide data on disease stage at diagnosis. Although the observed deviation from the optimal usage rate may reflect actual underutilization of radiotherapy during the study period, it is also possible that the Victorian study underreported overall radiotherapy utilization (and particularly palliative radiotherapy use, which often is delayed with respect to diagnosis) because the study was limited to reporting treatment at diagnosis. Munoz et al.27 conducted a patterns-of-care study involving a cohort of 785 patients with ovarian carcinoma who were identified from the 1991 SEER database. Five percent of these patients received radiotherapy, which was administered primarily to those with early-stage disease. This finding suggests that patterns of practice have changed, as radiotherapy currently is indicated mainly as a palliative measure for patients with metastatic ovarian carcinoma. Thus, it is not appropriate to compare practices reported in older studies with current recommendations. We were unable to find more recent patterns-of-care studies involving patients with ovarian malignancies.
In conclusion, the current study used an evidence-based method to estimate optimal radiotherapy usage rates for patients with cervical, ovarian, vaginal, and vulvar malignancies. The percentages of patients with cervical, ovarian, vaginal, and vulvar malignancies who should, according to the best available evidence, receive at least 1 course of radiotherapy are 58%, 4%, 100%, and 34%, respectively. These rates are similar to those observed in actual practice, although more patterns-of-care studies are needed to confirm this finding.
The authors thank Associate Professor David Roder for his provision of epidemiologic data from the South Australian Hospital-Based Cancer Registry. The authors also thank the Steering Committee of the Australian National Cancer Control Initiative and the reviewers, particularly Dr. Peter Grant, Dr. Alison Brand, Dr. Neville Hacker, Dr. David Allen, Dr. Alison Davis, and Dr. Katy Clarke.