Change in Cancer Pain Management in Korea Between 2001 and 2006: Results of Two Nationwide Surveys

Vol. 41 No. 1 January 2011 Journal of Pain and Symptom Management 93 Original Article Change in Cancer Pain Management in Korea Between 2001 and 2006: Results of Two Nationwide Surveys Sook Hee Hong, MD, Sang Young Roh, MD, Si Young Kim, MD, PhD, Sang Won Shin, MD, PhD, Chul Soo Kim, MD, PhD, Jin Hyuk Choi, MD, PhD, Sam Yong Kim, MD, PhD, Chang Yeol Yim, MD, PhD, Chang Hak Sohn, MD, PhD, Hong Suk Song, MD, PhD, and Young Seon Hong, MD, PhD Division of Medical Oncology (S.H.H., S.Y.R., Y.S.H.), Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul; Department of Internal Medicine (S.Y.K.), College of Medicine, Kyunghee University, Seoul; Department of Internal Medicine (S.W.S.), College of Medicine, Korea University, Seoul; Department of Internal Medicine (C.S.K.), College of Medicine, Inha University, Incheon; Department of Internal Medicine (J.H.C.), College of Medicine, Ajou University, Suwon-si, Gyeonggi-do; Department of Internal Medicine (S.Y.K.), College of Medicine, Chungnam National University, Daejeon; Department of Internal Medicine (C.Y.Y.), College of Medicine, Chonbuk National University, Jeonju-si, Jeollabuk-do; Department of Internal Medicine (C.H.S.), College of Medicine, Inje University, Busan; and Department of Internal Medicine (H.S.S.), College of Medicine, Keimyung University, Daegu, South Korea Abstract Context. In Korea, many health care professionals have shown increased concern about the management of cancer pain. Five years after a pain management guideline was distributed to Korean physicians, the Korean Society of Hospice and Palliative Care evaluated the change in cancer pain management. The period evaluated was between 2001 and 2006. Methods. We did a prospective, cross-sectional cancer pain survey on the change of the pain prevalence and pain intensity, its impact on daily activities and the adequacy of pain management between 2001 and 2006. Results. Overall, 7565 patients were enrolled from 72 cancer hospitals in the 2001 cancer pain survey and 7245 patients were enrolled from 63 cancer hospitals in the 2006 cancer pain survey. The overall prevalence of cancer pain and the percentage of patients reporting a negative pain management index were significantly decreased in the 2006 cancer pain survey compared with the 2001 cancer pain survey (44.9% vs. 52.1%, P < 0.0001 and 41.6% vs. 45.0%, respectively, P ¼ 0.0005). However, in 2006, physicians did not prescribe analgesics to 25.8% of the patients with severe pain and they did not adjust the prescribed analgesics properly in 47.4% of the patients with severe pain. Conclusion. Some improvement in cancer pain management was noted during the five years between 2001 and 2006. However, all of the physicians who care for Address correspondence to: Young Seon Hong, MD, PhD, Department of Internal Medicine, Seoul St. Mary Hospital, College of Medicine, Catholic University Ó 2011 U.S. Cancer Pain Relief Committee Published by Elsevier Inc. All rights reserved. of Korea, 505 Ban po dong, Seo cho Gu, Seoul 137-701, Korea. E-mail: ssuki76@catholic.ac.kr Accepted for publication: April 1, 2010. 0885-3924/$ - see front matter doi:10.1016/j.jpainsymman.2010.03.025

94 Hong et al. Vol. 41 No. 1 January 2011 cancer patients should pay more attention to cancer pain management, and an educational program for cancer pain management should be distributed to all of the physicians who care for cancer patients. J Pain Symptom Manage 2011;41:93e103. Ó 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. Key Words Cancer pain survey, analgesics, Korea Introduction Pain is one of most common symptoms of cancer, with a prevalence of more than 70% in patients with advanced stage disease. 1,2 Pain management is an important component of cancer treatment. Untreated or undertreated pain impairs physical and psychological health, functional status, and quality of life, in addition to increasing the economic cost. 3,4 Severe pain also is associated with more medical complications, refusal to receive proper treatment, and increased desire for hastened death. 5,6 Following the widespread dissemination of the three-level ladder of pain management by the World Health Organization (WHO), 7 opioid treatment has become widely accepted as the first-line approach for cancer-related pain, yielding satisfactory relief in as many as 90% of patients. 8,9 However, the majority of these patients still suffer from cancer pain. In Korea, the annual incidence of cancer is approximately 100,000 cases, resulting in 60,000 deaths each year. 10 Several organizations representing health care professionals have expressed concerns about cancer pain management. The Korean Society of Hospice and Palliative Care (KSHPC) was founded in 1998 to pursue the academic progress of hospice and palliative care medicine, and consequently influence health policies and laws. KSHPC, in cooperation with the Korean Cancer Study Group, prepared a preliminary cancer pain management guideline document in 2001. 11 The Korean Cancer Pain Assessment Tool, developed in 2003, is accepted as a reliable and valid instrument for assessing cancer pain in Korea. 12 The Korean government first published Cancer Pain Management Guidelines for Health Care Professionals in 2004. 13 Five years after distribution of the first pain management guideline document to Korean physicians, KSHPC constructed a baseline database to improve the outcome of cancer pain management and to evaluate 1) differences in the prevalence and intensity of cancer pain between 2001 and 2006; 2) patient attitudes and the degree of satisfaction with pain management; and 3) differences in the pain management index (PMI) to assess the adequacy of pain control between 2001 and 2006. Methods Participants This study was conducted by the KSHPC. We assumed that the incidence of pain in cancer patients was at least 50% on the basis of previous results. 1,2,14 Considering that this estimation was performed to calculate the number of patients within a validity rate of 1.5% at a statistical significance of 0.05 and confidence interval of 95%, the required number of patients was 4269. With a dropout rate of 20%, the corrected required number of patients was at least 5337. KSHPC proposed a nationwide cancer pain survey for members in 2001 and 2006. Voluntary participants were selected, with no limitations on the institution or department scale. All attending physicians providing care for cancer patients could participate in this study. Institutions and patients were recruited until the target sample size was more than 5337 patients, based on the statistically calculated sample size. The country was divided into eight sections according to the administrative district. Each section was assigned a principal investigator, and Y.S. Hong assumed responsibility as the overall principal investigator. The protocol was approved by the research ethics boards from all participating institutions. Participating institutions are listed in the Appendix.

Vol. 41 No. 1 January 2011 Change in Cancer Pain Management in Korea 95 Interview Protocol The 2001 and 2006 cancer pain surveys enrolled patients from each institution during one-week periods from April 9 to 14 and September 11 to October 14, respectively. The sample consisted of all patients who visited the outpatient clinic or were admitted in hospital during the study periods and who responded to the survey. Data collection for the surveys involved the administration of a semistructured interview conducted by trained interviewers. We consecutively enrolled patients at least 18 years of age with a pathologic diagnosis of cancer and who were able to complete or answer the questionnaire. Patients who did not answer questions voluntarily or were unable to complete the questionnaire due to impaired cognition were excluded from the study. Questionnaires were provided to physicians attending the patients, and individual patient s physicians were requested to complete additional questions on diagnosis, disease stage, Eastern Cooperative Oncology Group (ECOG) performance status, present treatment of cancer, cause of pain (cancer related vs. noncancer related vs. both), prescribed analgesics, and any adverse effects. Brief Pain Inventory Patients suffering from cancer-related pain completed a brief two-page questionnaire, the Brief Pain Inventory (BPI). The Korean version of the BPI, which measures both pain severity and the degree of pain interference with normal life, has been validated since 2003. We added a questionnaire based on the Korean version of the BPI in the 2006 survey, but could not do this for the 2001 survey. However, the 2001 questionnaire and the 2006 BPI had similar items. For the measurement of pain intensity, an 11-point numeric rating scale (0 ¼ no pain and 10 ¼ pain as bad as you can imagine) was used. Patients were asked to mark their pain intensity on the line. Because pain due to cancer varies significantly during the course of the day, patients were requested to rate pain as average pain in the last 24 hours. Patients were asked whether or not pain interfered with their general activity, mood, walking, work, and sleep (no interference or interference). In addition, in the 2006 cancer pain survey, we evaluated breakthrough pain. Breakthrough pain was characterized by asking patients to describe the frequency, intensity, and duration of episodic pain, and management options. Pain Management Index The PMI was used to evaluate the adequacy of analgesic use. We classified analgesics into three groups according to the WHO ladder. 15 To construct the index, analgesics were categorized as level 0 (none), level 1 (nonopioid), level 2 (so-called weak opioids), and level 3 (so-called strong opioids). Additionally, patient levels of pain on the modified BPI were grouped as follows: level 0 (pain rating of 0), level 1 (pain rating of 1e3), level 2 (pain rating of 4e6), and level 3 (pain rating of 7e10). The index was computed by subtracting the pain level from the analgesic level. Scores of 0 or higher were considered an indication of acceptable treatment. Patient Satisfaction Questionnaire Patients were asked about their satisfaction with pain relief as a result of treatment (very satisfactory, satisfactory, acceptable, unsatisfactory, or very unsatisfactory). Statistical Analysis All statistical analyses were performed using SAS statistical software (SAS Institute, Cary, NC). We used Chi-squared tests to compare percentages and independent sample t-tests to compare mean values. All significance levels refer to two-sided tests. A P-value of less than 0.05 was considered significant. Results Overall, 7565 patients were enrolled from 72 cancer hospitals for the 2001 cancer pain survey and 7245 patients were enrolled from 63 cancer hospitals for the 2006 survey. The mean ages of patients in the 2006 and 2001 cancer pain surveys were 58.2 and 56.4 years, respectively. The most commonly diagnosed cancer types were lung (19.2%), stomach (14.3%), colon-rectum (11.6%), breast (11.4%), lymphoma (5.7%), and pancreas (4.6%) in the 2006 cancer pain survey; and lung (14.9%), stomach (14.63%), breast (10.8%), colon-rectum (10.1%), lymphoma (9.4%), and leukemia (7.1%) in the

96 Hong et al. Vol. 41 No. 1 January 2011 2001 cancer pain survey. Among the patients experiencing cancer pain, 62.8% in 2006 and 41.0% in 2001 received anticancer treatment during the four weeks prior to the survey. The demographics of these patients are listed in Table 1. Prevalence, Intensity, and Frequency of Pain Of the 7245 cases screened in the 2006 cancer pain survey, 2782 (38.4%) patients complained of pain, whereas 463 (6.3%) patients had no pain but received analgesics. The overall prevalence of cancer pain was 44.9%. In the 2001 survey, 3591 (47.5%) of the 7565 patients screened complained of pain, whereas 346 (4.6%) had no pain but received analgesics. The overall prevalence of cancer pain was 52.1%. Interestingly, overall cancer pain prevalence was significantly decreased in 2006, compared with 2001 (P < 0.0001). Compared with the 2001 cancer pain survey, the prevalence of severe pain (pain score $7) was significantly less in the 2006 survey (10.6% vs. 15.3%, P < 0.0001). The mean pain intensity was 3.1 (2.4) in 2006 and 3.6 (2.4) in 2001, a significant difference (P < 0.0001) (Table 2). Pain intensity was not markedly different between male and female patients. However, pain intensity was significantly higher for inpatients admitted for advanced stage cancer and for those with poor ECOG performance status (P < 0.0001), compared with outpatients, those with early stage cancer, and good ECOG performance status. The patients reporting interference of pain with sleep and daily activities were more likely to experience severe pain (P < 0.0001). In terms of pain frequency, 59% of patients experienced daily pain, 13.3% reported pain three to four times per week, and 27.2% had pain one to two times per week in the 2006 survey. The following data were obtained in the 2001 survey: 59.4% of patients with daily pain, 14.9% with pain three to four times per week, and 22.6% reporting pain one to two times per week. Breakthrough Pain The 2006 survey evaluated the prevalence of breakthrough pain in addition to the 2001 criteria. In total, 38% of patients experienced breakthrough pain. In terms of the frequency of breakthrough pain, 32% of patients reported it once a day, 23% twice a day, 16% three times a day, 8% four times a day, and 21% more than five times a day. Overall, 71% of patients had breakthrough pain fewer than four times a day. Among the patients experiencing breakthrough pain more than five times each day, the mean number of times was 8.5 times each day. The frequency of breakthrough pain was significantly higher in the patients with more severe baseline pain (P < 0.0001). With regard to duration, 67% of patients experienced breakthrough pain for less than 30 minutes, 12% for 30e60 minutes, and 13% for more than 60 minutes. In total, only 41% of patients with breakthrough pain took medication for relief. The prevalence of breakthrough pain was significantly increased in inpatients (P < 0.0001), females (P ¼ 0.0024), and patients with advanced Table 1 Patients Demographics Characteristics Survey of 2006 Survey of 2001 P No. of patients (n) 7245 7565 Age (mean SD), years 58.2 12.8 56.4 13.6 Sex (%) Male/female 55/45 55/45 Admission status (%) Inpatient/outpatient 23/77 36/64 <0.001 ECOG performance status (%) 0/1/2/3/4 14/52/22/8/4 14/40/22/17/7 <0.001 Stage of disease (%) 1/2/3/4 5.4/9.9/21.1/63.6 6/16/23/55 <0.001 Patients with current anticancer treatment (%) Yes/no 62/38 41/56 <0.001

Vol. 41 No. 1 January 2011 Change in Cancer Pain Management in Korea 97 Table 2 Pain Intensity in the 2001 and 2006 Cancer Pain Surveys Intensity of Pain (NRS) Patients (%) in 2006 Survey Patients (%) in 2001 Survey P 0 479 (15.3%) 277 (7.2%) 1e3 1459 (46.6%) 1909 (49.7%) 4e6 861 (27.5%) 1068 (27.8%) 7e10 331 (10.6) 588 (15.3%) Mean (SD) 3.1 (2.4) 3.6 (2.4) <0.0001 NRS ¼ numeric rating scale. stage cancer (P ¼ 0.0038) and poor ECOG performance status (P < 0.0001) compared with outpatients, early stage cancer, and good ECOG performance status. The patients reporting pain interference with sleep and daily activities were also more likely to experience breakthrough pain (P < 0.0001). Impact of Pain on Daily Activities and Sleep In terms of pain interference, 67% and 55% of patients reported hindrance to daily activities in the 2006 and 2001 cancer pain surveys, respectively (P < 0.0001). Interference with daily activities was significantly increased for inpatients (P < 0.0001), patients with advanced stage cancer (P ¼ 0.004) and poor ECOG performance status (P < 0.0001), and individuals with more severe baseline pain (P < 0.0001). Patients reporting pain interference with sleep were more likely to experience pain that disrupted daily activities (P < 0.0001). More patients (54%) reported interference with sleep in the 2006 cancer pain survey than in the 2001 cancer pain survey (43%; P < 0.0001). Satisfaction with Pain Management The degree of overall satisfaction with pain management is presented in Table 3. Compared with the 2001 data, the percentage of patients who were satisfied or very satisfied Table 3 Satisfaction with Cancer Pain Management in the 2001 and 2006 Cancer Pain Surveys Degree of Satisfaction with Pain Management Patients (%) in 2006 Survey Patients (%) in 2001 Survey Very satisfied 6 4 Satisfied 36 33 Acceptable 45 42 Dissatisfied 12 19 Very dissatisfied 1 2 was significantly higher in the 2006 cancer pain survey than the 2001 survey (42% vs. 37%, respectively, P ¼ 0.0003) (Table 3). Satisfaction with pain control was significantly higher for female (P ¼ 0.0019) patients with good ECOG performance status (P ¼ 0.0220) and those reporting no interference with daily activities (P < 0.0001) or sleep (P < 0.0001). Patients reporting a low grade of satisfaction with pain management experienced increased pain intensity and prevalence of breakthrough pain vs. those with a high grade of satisfaction (P < 0.0001). Adequacy of Analgesic Management (Analgesic Adjustment and PMI) In 2006, 37% of patients with pain were not prescribed analgesics, compared with 34% of patients who were not prescribed analgesics in the 2001 survey (P ¼ 0.0057). The mean pain intensity score was 2.4 (2.3) in patients not administered analgesics in the 2006 pain survey, which was significantly lower than the estimated mean of pain intensity in the 2001 pain survey (mean [SD] ¼ 2.9 [2.2], P < 0.0001). Among the patients who did not take analgesics, the percentage with severe pain (pain score $7) was 6.6% in 2006, which was significantly lower than the number of patients with severe pain in the 2001 cancer pain survey (8.5%, P < 0.0001). The percentage of patients prescribed analgesics was markedly increased for inpatients vs. outpatients (P < 0.0001), males vs. females (P < 0.0001), patients with severe baseline pain vs. those without (P < 0.0001), and those with advanced stage vs. early stage disease (P < 0.0001). Patients reporting pain interference with sleep and daily activities were more likely to be prescribed analgesics than those who did not report such pain interference

98 Hong et al. Vol. 41 No. 1 January 2011 Table 4 Analgesic Adjustment in Response to Patients Pain Severity in the 2006 Cancer Pain Survey Number (%) of Patients Pain Intensity (NRS) Without Without Change in With Increase in With Decrease in 0 2207 (88.4%) 256 (10.2%) 26 (1.0%) 7 (0.3%) 1e3 713 (42.6%) 779 (46.6%) 133 (7.9%) 48 (2.9%) 4e6 230 (25.8%) 394 (44.3%) 195 (21.9%) 71 (8%) 7e10 75 (23.6%) 125 (39.3%) 92 (28.9%) 26 (8.1%) NRS ¼ numeric rating scale. (P < 0.0001). However, there was no significant difference in the degree of satisfaction with pain management between patients prescribed analgesics only and those who were not. In terms of analgesic adjustment, we evaluated the percentage of physicians who altered the prescription in response to patient complaints of pain. Physicians did not alter the prescribed analgesics for 39.3% of patients with severe pain and 44.3% of patients with moderate pain, and decreased the prescribed analgesics dose for 8.1% of patients with severe pain and 8% of patients with moderate pain (Tables 4 and 5). The PMI was calculated for all the patients experiencing pain. A significant proportion of patients (41%; 1207/2900)) experiencing pain had a negative score in the 2006 cancer pain survey (Table 6). The percentage of patients with negative PMI was significantly decreased in 2006, compared with 2001 (P ¼ 0.0005). Moreover, the percentage of patients reporting moderate and severe pain with a positive score was significantly higher in the 2006 cancer pain survey, compared with that in the 2001 cancer pain survey (moderate pain: 63.3% vs. 51.9%, respectively, P < 0.001; severe pain: 60.1% vs. 47.4%, respectively, P < 0.00001) (Tables 6 and 7). Prescribing Analgesics and Resulting Complications In terms of analgesic prescription, 62% of patients with pain were recommended opioid analgesics. A significant percentage of patients (44.3%) were prescribed strong opioid analgesics and 17.7% prescribed weak opioid analgesics in 2006. In 2001, 23% of patients were prescribed strong opioids and 11% were given weak opioids. Transdermal fentanyl was the most commonly prescribed strong opioid analgesic (23.2%) in 2006. Furthermore, 17.7% of the patients received controlled-release oxycodone, whereas 4.8% received sustained-release morphine. The most commonly used nonopioid analgesics were combination of acetaminophen 325 mg and tramadol HCl 37.5 mg (12.2%), nonsteroidal anti-inflammatory drugs (5.2%), and tramadol (4.9%). Significantly higher percentages of inpatients vs. outpatients (P < 0.0001), patients with advanced stage cancer vs. early stage cancer (P < 0.0001), and more severe baseline pain intensity vs. less severe baseline intensity (P < 0.0001) were administered strong opioid analgesics. Patients experiencing pain interference with sleep and daily activities were more often prescribed strong opioid analgesics than those without such pain (P < 0.0001). Table 5 Analgesics Adjustment in Response to Patients Pain Severity in the 2001 Cancer Pain Survey Number (%) of Patients Pain Intensity (NRS) Without Prescribed Analgesics Without Change in With Increase in With Decrease in 0 3628 (94.7%) 141 (3.81%) 7 (0.2%) 56 (1.5%) 1e3 725 (38.5%) 807 (42.8%) 125 (6.6%) 228 (12.1%) 4e6 362 (31.1%) 527 (45.2%) 175 (15.0%) 101 (8.7%) 7e10 171 (26.8%) 281 (44.1%) 138 (21.7%) 47 (7.4%) NRS ¼ numeric rating scale.

Vol. 41 No. 1 January 2011 Change in Cancer Pain Management in Korea 99 Table 6 Pain Management Index According to Pain Severity (NRS) in the 2006 Cancer Pain Survey PMI Number of Patients Pain Intensity (NRS) No. (%) of Patients with Inadequate Pain Control No. (%) of Patients with Adequate Pain Control 3 2 1 0 1 2 1e3 0 0 745 84 248 593 1670 745 (44.6%) 925 (55.4%) 4e6 0 282 45 136 429 0 892 327 (36.7%) 565 (63.3%) 7e10 80 16 39 203 0 0 338 135 (39.9%) 203 (60.1%) Total 1207 (41.6%) 1693 (58.4%) 2900 NRS ¼ numeric rating scale; PMI ¼ Pain Management Index. The most common complaint reported after analgesic prescription was constipation (36.3%). Other complaints registered in the 2006 cancer pain survey included somnolence (22.1%), nausea (19.9%), dry mouth (7.8%), and vomiting (6.3%). Discussion In a recent meta-analysis, the pooled prevalence of pain was >50% for all types of cancer. A recent pan-european survey of more than 5000 patients reported that more than 50% of patients suffered from moderate to severe cancer-related pain. 16 Several other national and international cancer surveys have been performed. 17e19 However, most of these have been reported as a one-time survey. Over the course of five years, the degree of cancer pain management may change, because physicians currently pay more attention to this issue. Korea is one of the most rapidly developing countries in terms of cancer pain management. KSHPC generated and distributed a Cancer Pain Management Guideline document in 2001. 11 Subsequently, an oral shortacting opioid, morphine sulfate, was made available in 2003. Oxycodone, another oral short-acting opioid, and transdermal fentanyl were launched in 2004 and 2005, respectively. The prevalence of cancer pain in the 2006 survey was 44.9%, which was significantly lower in relation to cancer pain in the 2001 survey (52.1%). However, with regard to the factors influencing cancer pain prevalence, the 2006 cancer pain survey included more outpatient clinic patients and those with better ECOG performance status, and more patients received anticancer treatment compared with the 2001 cancer pain survey. These factors may be related to the improvement of cancer management in Korean cancer patients. Table 7 Pain Management Index According to Pain Severity (NRS) in the 2006 Cancer Pain Survey PMI No. of Patients Pain Intensity (NRS) No. (%) of Patients with Inadequate Pain Control No. (%) of Patients with Adequate Pain Control 3 2 1 0 1 2 1e3 0 0 776 494 227 411 1908 776 (40.7%) 1132 (59.3%) 4e6 0 364 181 158 430 0 1133 545 (48.1%) 588 (51.9%) 7e10 173 80 66 287 0 0 606 319 (52.6%) 287 (47.4%) Total 1640 (45.0%) 2007 (55.0%) 3647 NRS ¼ numeric rating scale; PMI ¼ Pain Management Index.

100 Hong et al. Vol. 41 No. 1 January 2011 In terms of pain intensity and analgesic prescription, the percentage of patients with severe pain (pain $7) in 2006 was significantly decreased, along with mean pain intensity, compared with that in 2001. The overall percentage of analgesic prescription in the 2006 cancer pain survey also was decreased, compared with that in the 2001 survey (P ¼ 0.0057). However, the percentage of positive PMI score was significantly higher and the percentage of severe pain markedly lower in the 2006 cancer pain survey. These data were somewhat superior to those obtained from other countries that had validated and translated the PMI, in particular China (33%) 20 and Japan (30%). 21 Among the patients who did not take analgesics, mean pain intensity and percentage of severe pain were significantly decreased vs. those who did receive analgesics. The rate of analgesic prescription was less in 2006, while that of strong opioids was higher, compared with 2001 (43.3% vs. 23%, respectively). Following the provision of cancer pain management guidelines to Korean physicians in 2001, physicians and patients may have been less hesitant to prescribe and receive opioid analgesics. However, increased percentage of positive PMI scores alone may not be adequate to support the conclusion that pain was controlled better in 2006 vs. 2001. This is because patients treated with strong opioids are considered adequately managed despite the severity of pain and treatment dosage. 22,23 The present study reports that 25.8% of patients with moderate pain and 23.6% of patients with severe pain were not prescribed analgesics, although about 8% of these patients received analgesics at reduced doses or with lower potency. Adequate pain control involves the appropriate use of opioids according to pain intensity and rapid opioid titration. Korean physicians should pay more attention to pain management of cancer patients not only in terms of analgesic prescription, but also in sufficient doses and dosage titration. In view of this limitation, modified PMIs (such as the Amsterdam PMI ) have been developed and validated. 24 The validity and application of this type of modified PMI in Korea must be considered. A significant percentage of patients suffered breakthrough pain. About one-half to twothirds of patients with cancer pain experienced breakthrough pain, with about half of these cases reporting good pain control. 25,26 This pain is associated with higher pain scores and more interference with function. 26 In the 2006 survey, 38% of patients reported breakthrough pain, of whom only 41% obtained medical relief. The unpredictable and heterogeneous nature of this pain made management difficult. However, according to the Veteran s Affair Medical Center, following expert intervention for just one week among the 70% of patients initially reporting breakthrough pain, only half (36%) still experienced pain after management. 27 This report suggested that aggressive analgesics therapies not only could improve the background pain but also could reduce the breakthrough pain prevalence. 27 In Korea, commonly used medicines for managing breakthrough pain at outpatient clinics include shortacting opioids, such as oxycodone, morphine sulfate, and hydromorphone. Korean physicians should pay considerably more attention to breakthrough pain, and prescribe appropriate doses and routes of short-acting opioids. The present study has some limitations. Initially, data were collected mainly from cancer hospitals, most of which were members of the KSHPC. The patients included in this study were possibly managed by cancer specialists and thus do not represent the whole country. General Korean cancer patients other than cases treated at these centers are probably undertreated for cancer pain. We only surveyed the BPI of patients who specifically responded to the interview. The most significant causes of nonresponse to the interview were refusal and hospital visit by caregivers instead of patients. These patients would have pain management problems. However, we have not further assessed the characteristics of these patients. The assessment tools used were not validated in the 2001 cancer pain survey. The Korean version of the BPI was recently introduced and validated in 2004. 12 In the 2006 survey, we generated questionnaires similar to the Korean BPI. However, in 2001, we had just started to pay attention to cancer pain, and thus the questionnaire was not fully prepared. Future studies using the Korean BPI will be meaningful for Korean cancer patient surveys. Data from the present study do not reflect the pain management of cancer patients during the overall illness, when considering the

Vol. 41 No. 1 January 2011 Change in Cancer Pain Management in Korea 101 cross-sectional survey design, especially when pain is simply evaluated at its average intensity. In conclusion, the present report provides the first large-scale evaluation of the prevalence, severity, and treatment results of cancer pain in Korea, and examines the changes in cancer pain management at five years after distribution of the guideline document to Korean physicians. Some improvement in cancer pain management was noted during the five-year period. However, more than 40% of patients were undertreated for cancer pain, and more than two-thirds were not prescribed analgesic adjustment. We propose that all physicians caring for cancer patients should pay more attention to cancer pain management, and an educational program focusing on this issue should be distributed to all physicians treating cancer. Disclosures and Acknowledgments This study was supported by the Korean Society for Hospice and Palliative Care and Janssen Korea. References 1. Daut RL, Cleeland CS. The prevalence and severity of pain in cancer. Cancer 1982;50:1913e1918. 2. Goudas LC, Bloch R, Gialeli-Goudas M, Lau J, Carr DB. The epidemiology of cancer pain. Cancer Invest 2005;23:182e190. 3. Fortner BV, Demarco G, Irving G, et al. Description and predictors of direct and indirect costs of pain reported by cancer patients. J Pain Symptom Manage 2003;25:9e18. 4. Cleeland CS. The impact of pain on the patient with cancer. Cancer 1984;54:2635e2641. 5. Mystakidou K, Parpa E, Katsouda E, Galanos A, Vlahos L. Pain and desire for hastened death in terminally ill cancer patients. Cancer Nurs 2005;28: 318e324. 6. O Mahony S, Goulet J, Kornblith A, et al. Desire for hastened death, cancer pain and depression: report of a longitudinal observational study. J Pain Symptom Manage 2005;29:446e457. 7. World Health Organization. Cancer pain relief: With a guide to opioid availability. Geneva: World Health Organization, 1996. 8. Levy MH. Pharmacologic treatment of cancer pain. N Engl J Med 1996;335:1124e1132. 9. Zech DF, Grond S, Lynch J, Hertel D, Lehmann KA. Validation of World Health Organization Guidelines for cancer pain relief: a 10-year prospective study. Pain 1995;63:65e76. 10. Ministry of Health and Welfare. Annual report of the Central Cancer Registry in Korea. Seoul: Ministry of Health and Welfare, 2003. 11. The Korean Society for Hospice and Palliative Care, Korean Cancer Study Group. Guidelines of cancer pain management. Seoul: Koonja Publishing, 2001. 12. Yun YH, Mendoza TR, Heo DS, et al. Development of a cancer pain assessment tool in Korea: a validation study of a Korean version of the Brief Pain Inventory. Oncology 2004;66:439e444. 13. Ministry of Health and Welfare. Cancer pain management guideline. Seoul: Ministry of Health and Welfare, 2004. 14. Hyun MS, Lee JL, Lee KH, et al. Pain and its treatment in patients with cancer in Korea. Oncology 2003;64:237e244. 15. Cleeland C. Research in cancer pain. What we know and what we need to know. Cancer 1991;67: 823e827. 16. Breivik H, Cherny N, Collett B, et al. Cancerrelated pain: a pan-european survey of prevalence, treatment, and patient attitudes. Ann Oncol 2009; 20:1420e1433. 17. Von Roenn JH, Cleeland CS, Gonin R, Hatfield AK, Pandya KJ. Physician attitudes and practice in cancer pain management. A survey from the Eastern Cooperative Oncology Group. Ann Intern Med 1993;119:121e126. 18. Larue F, Colleau SM, Brasseur L, Cleeland CS. Multicentre study of cancer pain and its treatment in France. Br Med J 1995;310:1034e1037. 19. Hsieh RK. Pain control in Taiwanese patients with cancer: a multicenter, patient-oriented survey. J Formos Med Assoc 2005;104:913e919. 20. Wang XS, Mendoza TR, Gao SZ, Cleeland CS. The Chinese version of the Brief Pain Inventory (BPI-C): its development and use in a study of cancer pain. Pain 1996;67:407e416. 21. Okuyama T, Wang XS, Akechi T, et al. Adequacy of cancer pain management in a Japanese Cancer Hospital. Jpn J Clin Oncol 2004;34:37e42. 22. Cleeland CS, Portenoy RK, Rue M, et al. Does an oral analgesic protocol improve pain control for patients with cancer? An intergroup study coordinated by the Eastern Cooperative Oncology Group. Ann Oncol 2005;16:972e980. 23. Cleeland CS, Gonin R, Hatfield AK, et al. Pain and its treatment in outpatients with metastatic cancer. N Engl J Med 1994;330:592e596. 24.deWitR,vanDamF,LoonstraS,etal.The Amsterdam Pain Management Index compared to eight frequently used outcome measures to

102 Hong et al. Vol. 41 No. 1 January 2011 evaluate the adequacy of pain treatment in cancer patients with chronic pain. Pain 2001;91:339e 349. 25. Portenoy RK, Hagen NA. Breakthrough pain: definition, prevalence and characteristics. Pain 1990;41:273e281. 26. Portenoy RK, Payne D, Jacobsen P. Breakthrough pain: characteristics and impact in patients with cancer pain. Pain 1999;81:129e134. 27. Hwang SS, Chang VT, Kasimis B. Cancer breakthrough pain characteristics and responses to treatment at a VA medical center. Pain 2003;101:55e64. Appendix Institutions Participating in the 2001 Cancer Pain Survey Andong Hospital, Ajou University Medical Center, Asan Medical Center, Baptist Hospital, Bohun Hospital, Bundang Jesaeng Hospital, Busan Medical Center, Daegu Fatima Hospital, Changwon Fatima Hospital, Chonbuk National University Hospital, Chosun University Hospital, Chungbuk National University Hospital, Chungang University Hospital, Chungnam National University Hospital, Daegu Catholic University Medical Center, Dankook University Hospital, Dongguk University Gyongju Hospital, Gyeongsang National University Hospital, Ewha Womens University Tongdaemun Hospital, Ewha Womens University Mokdong Hospital, Gachon University Gil Hospital, Hallym University Kangdong Sacred Heart Hospital, Hallym University Kangnam Sacred Heart Hospital, Handong Universiy Sunlin Hospital, Hanyang University Hospital, Inha University Hospital, Inje University Pusan Paik Hospital, Inje University Seoul Paik Hospital, Keimyung University Dongsan Medical Center, Konkuk University Medical Center, Konyang University Hospital, National Cancer Central Hospital, Korea University Anam Hospital, Korea University Ansan Hospital, Korea University Guro Hospital, Kosin Universiy Gospel Hospital, Kwangju Christian Hospital, Kyunghee Medical Center, Maryknoll Hospital, Myongji Hospital, Pochon CHA University Bundang CHA Hospital, Pusan National University Hospital, SAM Anyang hospital, Seoul National University Bundang Hospital, Seoul National University Hospital, Severance Hospital, Soonchunhyang University Hospital, Soonchunhyang University Bucheon Hospital, Soonchunhyang University Cheonan Hospital, Sungkyunkwan University Kangbuk Samsung Medical Center, The Catholic University of Korea Daejeon St. Mary s Hospital, The Catholic University of Korea Holy Family Hospital, The Catholic University of Korea Incheon St. Mary s hospital, The Catholic University of Korea Kangnam St. Mary s Hospital, The Catholic University of Korea St. Mary s Hospital, The Catholic University of Korea Uijeongbu St. Mary s Hospital, Ulsan University Hospital, Wonju Christian Hospital, Wonkwang University Hospital, Yeonggwang General Hospital, Yeungnam University Hospital, Youngdo Hospital. Institutions Participating in the 2006 Cancer Pain Survey Andong Hospital, Ajou University Medical Center, Asan Medical Center, Bohun Hospital, Boramae Medical Center, Daegu Fatima Hospital, Chonbuk National University Hospital, Chonnam National University Hospital, Chonam Hospital, Chosun University Hospital, Chungang University Yong-San Hospital, Chungnam National University Hospital, Daegu Catholic University Medical Center, Dankook University Hospital, Dong-A University Medical Center, Dongguk University Gyongju Hospital, Eulji University Eulji General Hospital, Ewha Womens University Tongdaemun Hospital, Ewha Womens University Mokdong Hospital, Gangneung Asan Hospital, Gachon University Gil Hospital, Gyeongsang National University Hospital, Hallym University Scared Heart hospital, Hallym University Kangdong Sacred Heart Hospital, Hallym University Kangnam Sacred Heart Hospital, Hallym University Hangang Scared Heart Hospital, Hanyang University Guri Hospital, Hanyang University Hospital, HNIC Ilsan Hospital, Inha University Hospital, Inje University Ilsan Paik Hospital, Inje University Pusan Paik Hospital, Inje University Sanggye Paik Hospital, Inje University Seoul Paik Hospital, Jeonjinsang Hospital, JeonJu Jesus Hospital, Keimyung University Dongsan Medical Center, Konyang University Hospital, Korea University Anam Hospital, Korea University Ansan Hospital, Korea University Guro Hospital, Kosin Universiy Gospel Hospital, Kwangju Christian Hospital, Kyunghee Medical Center, Kyungpuk National University Hospital, Maryknoll Hospital, National Medical Center, Pochon

Vol. 41 No. 1 January 2011 Change in Cancer Pain Management in Korea 103 CHA University Bundang Cha Hospital, Pusan National University Hospital, Seonam University Hospital, Seoul Adventist Hospital, Seoul National University Hospital, Severance Hospital, Soonchunhyang University Hospital, Soonchunhyang University Bucheon Hospital, Soonchunhyang University Cheonan Hospital, Suncheon St. Carollo hospital, Sunggabokji Hospital, Sungkyunkwan University Samsung Seoul Hospital, Sungkyunkwan University Kangbuk Samsung Medical Center, Sungkyunkwan University Masan Samsung Hospital, Yongdong Severance Hospital, The Catholic University of Korea Daejeon St. Mary s Hospital, The Catholic University of Korea Holy Family Hospital, The Catholic University of Korea Incheon St. Mary s hospital, The Catholic University of Korea Kangnam St. Mary s Hospital, The Catholic University of Korea St. Mary s Hospital, Ulsan University Hospital, Wonju Christian Hospital, Wonkwang University Hospital, Yeosu Chonnam Hospital, Yeungnam University Hospital.