The 7th American Urological Association and the Japanese Urological Association International Affiliate Society Meeting

Abstract

The American Urological Association (AUA) and the Japanese Urological Association (JUA) have been working together to extend collaboration in the science and art of urology. On behalf of JUA, we are pleased to announce the 7th AUA/JUA International Affiliate Society Meeting at the 108th Annual Meeting of AUA (19–23 May 2012, Atlanta, GA, USA). We are grateful for the support of AUA, with which this joint program was prepared and materialized. We would also like to express our sincere appreciation to all people concerned, including the moderators, lecturers and panelists of both societies. To stimulate better communication between the two societies, this year's joint program has more case discussions than previous ones, covering two topics each in oncology (renal cell carcinoma [RCC] and castration-resistant prostate cancer [CRPC]) and benign urology (overactive bladder [OAB] and urinary tract infection [UTI]). One symposium and two state-of-the-art lectures compose the framework of the program. We look forward to the participation of many members of both societies in this joint program. Last, we would like to thank Dr Sushil Lacy, AUA President; Dr Gopal Badlani, AUA Secretary General; and Dr Robert Flanigan, Program Coordinator, for their dedication to develop and deepen the mutual relationship between AUA and JUA. Yukio Homma M.D., JUA President Hidehiro Kakizaki M.D., Chair, JUA International Committee Joseph A Smith Jr M.D. Department of Urologic Surgery, Vanderbilt University, Nashville, TN, USA Surgical treatment of prostate cancer can have profound adverse effects on quality of life. Without question, technical factors can contribute to surgical outcomes, and studies show improved results for highly experienced surgeons and for high volume hospital settings. Less clear is how much surgical approach itself affects outcomes. There is controversy about whether a robotic-assisted laparoscopic approach provides better results that open surgery for surgeons of comparable experience. Vanderbilt University has been one of the highest volume centers in the USA for prostate cancer surgery, with a data base of over 2000 radical retropubic prostatectomy patients and over 3500 robotic-assisted laparoscopic procedures. Comparative outcome data consistently show decreased blood loss and transfusion requirement with robotic-assisted laparoscopic prostatectomy (RALP), consistent with virtually all other reports. Length of hospital stay is targeted for 1 day regardless of surgical approach, but RALP patients meet this goal more frequently. Bladder neck contracture has occurred in fewer than 1% of the RALP group. The most important quality of life (QOL) outcome measures are postoperative urinary continence and erectile function. Because studies show comparable oncological results, QOL results are of paramount importance. Measures used by some surgeons to improve continence results, such as bladder neck preservation, anterior urethral suspension or posterior reconstruction, can be accomplished with either open or laparoscopic surgery. Both approaches seek to maximize urethral length. Overall, no consistent advantage for RALP or open surgery has been shown. Erectile function results correlate strongly with patient age and preoperative function. Without doubt, the fascial coverings of the prostate are more readily visualized with laparoscopic magnification, permitting dissection between the lateral pelvic fascia and the prostate to provide an optimal combination of tumor control and preservation of neural tissue. Again, though, no consistent advantage for robotic surgery has been shown. Highly experienced surgeons might be able to obtain near comparable results with open or robotic surgery for low risk cancers. However, surgeons with a more moderate volume practice more reliably and consistently report more favorable results with RALP. Furthermore, it has been our experience that RALP provides superior tumor control for high-risk cancers, as the antegrade approach allows early release of the prostate from the rectum and wide resection of the prostate pedicles. In the USA and, increasingly, worldwide, surgeons have adopted RALP as the preferred approach for radical prostatectomy. Shunichi Namiki M.D. and Yoichi Arai M.D. Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan Objectives: Radical prostatectomy (RP) is a standard treatment for patients with localized prostate cancer and a life expectancy of more than 10 years who accept the risk of treatment-related complications. Under these circumstances, health-related quality of life (HRQOL) outcome in patients who are treated with each treatment modality has become a pivotal concern among both patients and physicians. Urinary incontinence and erectile dysfunction represent the principal sources of postoperative adverse events for patients who have undergone RP, even with nerve-sparing techniques. Race and ethnicity impact on satisfaction with care and other outcomes and there is growing interest in quality of life among Asian men with prostate cancer. We compared the evolution of disease-specific HRQOL during the first 2 years after RP between Japanese and American men with localized prostate cancer. Methods: A total of 324 Japanese men with localized prostate cancer, who underwent RP, enrolled in a longitudinal outcomes study. The men were treated at Tohoku University Hospital and two of its affiliated hospitals. A total of 307 American men with localized prostate cancer, who underwent RP at UCLA, also enrolled in a longitudinal outcomes study. We evaluated urinary and sexual HRQOL using the University of California Los Angeles, Prostate Cancer Index (PCI). Results: At 2 years after RP, the sexual function of 22% of Japanese men and 35% of American men had fully returned to the baseline levels. In addition, American men were more likely than Japanese men to regain their baseline sexual function by 24 months after treatment. After RP, the Japanese men showed significantly equivalent or better sexual bother scores (less distress) than did the American men at all postoperative time points. The sexual bother of just 24% and 40% American men returned to baseline levels at 1 and 6 months postoperatively, 39% and 73% Japanese men showed similar tendencies. Urinary function scores decreased from baseline to a nadir at 1 month after RP and then continued to increase through to 24 months postoperatively. Multivariate analyses showed a non-linear trend of recovery, and an interaction between this trend and country with regard to urinary function (control) and bother after RP (both P < 0.0001). Conclusions: We found that cultural differences between Japanese and American men independently predicted the pattern of disease-specific HRQOL recovery up to 24 months after RP for localized prostate cancer. Yoshihiko Tomita M.D., Ph.D. Department of Urology, Yamagata University Faculty of Medicine, Yamagata, Japan Introduction: In the past 5 years, new drugs have been shown to be effective for renal cell carcinoma (RCC). Accordingly, treatment strategy for metastatic RCC (mRCC) patients has changed drastically. However, controversial issues have not been fully discussed and solved. Objectives: To understand the present strategy for mRCC, especially combination therapy with surgery and systemic drug therapy. To clarify the decision-making process in a challenging case, through discussion of several clinical settings. To possibly delineate what is an urgent question to be asked. The moderator will present a case and ask each panelist's opinion from time to time. General questions will also be asked at decision-making points as a choice of a treatment modality not only for panelists, but also participants. Case: A 54-year-old male complaining of abdominal pain presented in June 2009. Computed tomography (CT) scan showed a left RCC and a large retroperitoneal mass at the bifurcation of the aorta. Further examination with magnetic resonance imaging and an additional CT scan confirmed left RCC, but the retroperitoneal mass had the possibility of being a malignant lymphoma. The Memorial Sloan-Kettering Cancer Center (MSKCC) risk criteria: Poor (or intermediate), elevated corrected serum Ca, low hemoglobin, needs systemic therapy at initial diagnosis if it is a metastasis. Question 1: What is your first-line treatment? And explain its reason. Left radical nephrectomy was carried out. Pathology: clear cell carcinoma. Biopsy and pathological examination of the retroperitoneal mass showed metastasis of RCC. Question 2: What is your next treatment? Resection of retroperitoneal mass showed that it is RCC metastasis. Question 3: What is an optimal end-point in this case? And why? Conclusions: Throughout the discussion with the Japanese Urological Association and American Urological Association experts, the panel will try to draw a conclusion in terms of multimodal treatment exploring a better outcome. Robert Uzzo M.D., F.A.C.S. Department of Surgery, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA, USA The standard of care for renal cell carcinoma (RCC) is surgical resection as monotherapy or as part of a multimodal approach. In patients presenting with localized disease, radical nephrectomy alone is associated with a favorable prognosis, whereas patients with advanced disease are rarely cured. A significant number of patients undergoing surgery for localized or locally advanced RCC experience recurrence, suggesting that there are some individuals in whom surgical excision is necessary but insufficient due to the presence of micrometastatic disease. In these patients, the development of effective neoadjuvant and adjuvant strategies is imperative. While initial efforts with radiotherapy and immunotherapeutic agents have met with little success, there is considerable interest in the use of targeted anti-angiogenic agents for patients presenting with advanced disease. Answer 1: In the patient presented, he is clinically stage 4 radiographically at presentation. Given his young age and good performance status, our initial therapy would be cytoreductive nephrectomy after biopsy of the retroperitoneal mass assured the discontiguous retroperitoneal lesion to be RCC. While historically performed primarily as a palliative measure, two prospective randomized trials have now demonstrated a survival benefit for patients with metastatic RCC treated with nephrectomy followed by INF-α versus patients who received immunotherapy alone. These data have been extrapolated to support cytoreductive nephrectomy in the targeted therapy era as well although the role of nephrectomy in the setting of advanced disease using antiangiogenics continues to be defined. A survival benefit to cytoreductive nephrectomy was recently confirmed in a large, retrospective population-based study as well, where patients with metastatic RCC who did not undergo surgery had a 2.5-fold increase risk of overall and cancer-specific mortality. As such, the treatment paradigm which has evolved for advanced RCC has been initial CN followed by system therapy unless the metastases are fully resectable in a highly functional patient. In those instances cytoreduction with metastasectomy is considered first line followed by delayed systemic therapy as indicated. Answer 2: Metastasectomy has long been considered the next step for young, otherwise healthy individuals with limited metastatic disease. While the data all suffer from biases as retrospective cohort series, they appear relatively consistent in the themes that 3 prognostic factors are most important when considering resection of metastatic disease: the number of metastases (solitary is better than multifocal), the disease free interval (longer is better than shorter or synchronous) and the location of the metastases (lung is better than lymph node and adrenal while bone, CNS and visceral (hepatic) are worse). We have recently reviewed our experience in patients undergoing surgery for advanced RCC to investigate predictors of mortality in patients with metastatic RCC undergoing CN. Consistent with previous reports we found that poor performance status, higher tumor grade, sarcomatoid features, and visceral metastases (specifically liver in our analysis) were associated with a shorter overall survival following surgery. On the other hand, patients who were able to undergo resection of metastases were found to have improved survival. Although a strong selection bias exists in such an analysis, whereby patients with a better ECOG PS and lower volume disease are more likely to undergo additional surgery, a survival benefit to the resection of metastases from RCC has been demonstrated, and metastasectomy should therefore remain part of the treatment arsenal when technically feasible and biologically logical. Answer 3: The decision as to whether to begin systemic therapy in a patient with fully resected advanced RCC is a difficult one since there are no level 1 data on the topic. Some information may be gleaned from ongoing adjuvant studies using targeted therapy for at risk patients. The contemporary era of targeted therapy for RCC has focused on inhibition of the angiogenesis pathway implicated in RCC tumorigenesis, and current FDA approved first line agents for mRCC include the vascular endothelial growth factor (VEGF) neutralizing antibody bevacizumab (Avastin®, Genentech, Inc., San Francisco, CA, USA) in combination with interferon alpha, the VEGF receptor and platelet-derived growth factor (PDGF) receptor targeted tyrosine kinase inhibitors (TKIs) sorafenib (Nexavar®, Bayer Pharmaceuticals Corp./Onyx Pharmaceuticals, Inc., Pittsburgh, PA, USA), sunitinib (Sutent®, Pfizer, Inc., New York, NY, USA) and pazopanib (Glaxo Smith Kline, Inc., Brentford, Middlesex, UK), the mammalian target of rapamycin inhibitor (mTOR) temsirolimus (Torisel®, Pfizer, Inc, New York, NY, USA), and the mTOR inhibitor everolimus (Affinitor®, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA) following failure of treatment with sunitnib or sorafenib. Prospective randomized trials have demonstrated that a proportion of mRCC patients treated with TKIs exhibit objective primary tumor response (10–31%), while a larger proportion demonstrate disease stabilization (26–74%) and increased progression free survival when compared to placebo and immunotherapeutic agents. These findings have resulted in increased interest in use of TKI therapy in the adjuvant setting for primary tumors with high risk pathologic features following extirpative surgery, and in the neoadjuvant setting to reduce tumor burden, treat micrometastatic disease, and help select patients that may best respond to surgical therapy. The use of anti-angiogenic therapy in the adjuvant setting for high-risk RCC is a current area of intense interest. Both vascular endothelial growth factor (VEGF) neutralizing antibodies and tyrosine kinase inhibitors, which block the receptors of VEGF, have been shown to improve outcomes in mRCC. A randomized, controlled, phase III (ASSURE) trial evaluating sorafenib and sunitinib for high risk RCC in the adjuvant setting was recently completed in 2010 after accrual of 1944 patients. Disease free survival was the primary end point of this trial with overall survival and quality of life defined as the secondary end points (NCT00326898, http://www.clinicaltrials.gov). Adjuvant trials evaluating other multi-targeted VEGF receptor inhibitors (pazopanib) and mTor inhibitors (everolimus) are currently accruing with the endpoint being PFS. Whereas antiangiogenic therapies are rarely curative in cases of mRCC and often require lifelong therapy, the decision to begin treatment in patients that have a good performance status and are otherwise radiographically free of disease remains controversial and often subjective based upon risk tradeoffs and goals agreed upon between patient and clinician. The bias at our institution is not to begin systemic therapies in the setting of fully resected disease without any evidence of radiographic recurrence or progression. Norihiko Tsuchiya M.D. Department of Urology, Akita University School of Medicine, Akita, Japan Molecular-targeted agents, such as tyrosine kinase inhibitors (TKI) and mammalian target of rapamycin (mTOR) inhibitors, are currently mainstream therapies for patients with metastatic renal cell carcinoma (RCC). Although clinical decisions are made according to guidelines based on a number of important clinical trials, we often encounter cases to which these guidelines cannot be directly applied. The case presented by Professor Tomita is just such a case, and is one that would cause many arguments, even among experts on RCC. Answer 1: I believe that diagnostic biopsy of retroperitoneal tumor is mandatory, because treatment strategies differ for “metastasis” and “malignant lymphoma.” This case is a situation in which systemic therapy is needed if the retroperitoneal tumor is “metastasis,” indicating that curative surgical resection of the tumor is technically impossible and nephrectomy is difficult or unsuitable. Therefore, a percutaneous needle biopsy should be carried out for accurate pathological diagnosis of the tumor before systemic treatment. Injudicious systemic therapy without definite pathological diagnosis should be avoided. If pathology reveals a “malignant lymphoma,” systemic chemotherapy will be administered. In a case where pathology of the tumor is clear cell carcinoma, systemic molecular-targeted therapy with sunitinib will be selected, which has the highest response rate among TKI available in Japan. Answer 2: If both the retroperitoneal tumor and left kidney are judged to be curatively resectable after systemic targeted therapy, radical nephrectomy and resection of the retroperitoneal tumor will be considered. If the cytoreductive nephrectomy is clinically effective, radical nephrectomy will be considered. In this case, only nephrectomy was carried out, suggesting that the retroperitoneal tumor was unresectable. Sunitinib will be continued until progression and switched to mTOR in case of progression. Because complete resection of metastatic lesions has been indicated to offer a survival advantage, resection of the peritoneal tumor will be aggressively considered if the tumor showed further shrinkage and no new metastases were present. Answer 3: This case achieved a complete response (CR) with systemic therapy and surgery. The end-point of this case will be a durable CR without maintenance therapy. However, there is no consensus on the best treatment strategy after achieving CR with TKI or TKI and local therapy. The following three options are available: discontinuation of TKI, discontinuation of TKI after a certain period of time, and continuation of TKI at full or reduced doses. A recent retrospective study (Albiqes L et al., J. Clin. Oncol. 2012) showed that approximately 50% of patients who achieved CR with TKI and local therapy showed no recurrence on short-term follow up. Disadvantages of the continuation of TKI include drug resistance and persistent adverse events (AE), whereas discontinuation of TKI has disadvantages in terms of the possible risk of rapid progression as a result of a rebound effect. However, re-challenge of the same TKI showed a partial response in 64% of patients with recurrence after cessation of TKI, suggesting that sensitivity to the same TKI remains in many patients. In addition, discontinuation of TKI frees patients from worrisome AE. Because the risk of recurrence does not appear to differ among the three options in patients with a surgical CR, there might be many benefits to discontinuing TKI, and initiating treatment with the same agent in the case of recurrence of a retroperitoneal tumor considered to be curatively resected. Masayuki Takahashi M.D., Ph.D. Department of Urology, The University of Tokushima Graduate School, Tokushima, Japan The patient presented is relatively young – 54 years-of-age. He had three risk factors of the Memorial Sloan-Kettering Cancer Center (MSKCC) risk classification, such as elevated corrected serum calcium, low hemoglobin level and metastasis at initial presentation if retroperitoneal mass is metastasis. That shows that he did not have a high serum lactate dehydrogenase level with good performance status. If a treatment strategy was decided on according to the reported clinical guideline, temsirolimus should be chosen, because the patient might have poor risk. Some treatment efficacy would be expected of temsirolimus, even if nephrectomy was not carried out. However, in the situation where the retroperitoneal mass might not be a malignant lymphoma, but a metastasis of a renal cell carcinoma, the main purpose of systemic therapy is to confirm if the retroperitoneal mass would be shrunk by the systemic therapy. Considering the aforementioned situation, systemic therapy that has a high degree of tumor shrinkage with a high response rate should be chosen. In addition, the patient was not old, and had a good performance status. My answer for Q1 is sunitinib for the first-line treatment. Even if a molecular targeted agent with high efficacy is continuously administered, complete response would be very rarely expected. If metastases to other organs than the retroperitoneal mass did not appear, resection of the retroperitoneal mass would be planned as my answer for Q2. If complete resection could be achieved, I would not choose the adjuvant therapy, but close follow up, so as not to give the patients unnecessary exposure to adverse events by molecular targeted agents, because the patient might not have recurrence for a while after complete resection of metastasis. If resection of the retroperitoneal mass was incomplete, I would restart sunitinib. In this situation, a cure is not expected. Therefore, the optimal end-point should be to maintain good quality of life as long as possible with some efficacy for tumors as my answer for Q3. Tomohiko Ichikawa M.D., Ph.D. Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan We report one patient with castration-resistant prostate cancer (CRPC) and discuss the treatment options. A 60-year-old man was referred to our outpatient clinic for an elevated serum prostatic-specific antigen (PSA) of 203 ng/mL in November 2003. He was diagnosed with prostate cancer (Gleason Score 3 + 4 = 7, T3 N1 M1b, extent of disease [EOD] 2) and received androgen deprivation therapy with luteinizing hormone-releasing hormone (LHRH) agonist every 3 months with bicalutamide (80 mg/mL), resulting in a PSA nadir of 0.58 ng/mL. His PSA level had been stable for 9 months, thereafter it gradually increased to 2.0 ng/mL in July 2004. Question 1: What would have been your treatment options to consider and your choice at this point? After checking the effect of bicalutamide withdrawal on the PSA level, flutamide (375 mg/day) was started. The PSA level was decreased slightly from 13.1 to 11.0 ng/mL, then increased again to 86 ng/mL in March 2005. Question 2: What would have been your treatment options to consider and your choice at this point? After checking the effect of flutamide withdrawal, estramustine was started. The PSA level was decreased from 94 ng/mL to a nadir of 34 ng/mL in May 2005. Estramustine had been continued until December 2006, when the PSA level was 90 ng/mL. Then zoledronic acid was started (4 mg/4 weeks) in December 2006, which was discontinued later because of extraction of teeth in January 2008. In February 2007, the PSA level was 240 ng/mL, and oral administration of dexamethasone (1.0 mg/day) was started. In March 2007, he complained of paraparesis as a result of progression of both Th6 and Th8 bone metastases. His performance status (PS) was 2, and the serum testosterone level was 0.10 ng/mL. Question 3: What would have been your treatment options to consider and your choice at this point? External beam radiation therapy (EBRT) to the metastases lesion, 30 Gy in 10 fractions, was carried out and the paraparesis improved. The PSA level dramatically dropped to a nadir of 2.1 ng/mL at 6 months after the EBRT, and then had been lower than 4.0 ng/mL until March 2008. Then the PSA level gradually increased to 5.4 ng/mL in June 2008. A bone scan showed the progression of bone metastases to EOD 3. His PS was still 2 at this point. Question 4: What would have been your treatment options to consider and your choice at this point? The patient received low-dose and long-interval docetaxel treatment (i.e. 50 mg/m2 every 6 weeks) while his LHRH agonist and oral dexamethasone administration were continued. After two courses of this therapy, the PSA level decreased to 3.4 ng/mL. He was maintained on the same chemotherapy. The PSA level was 3.2 ng/mL in September 2009, 9.7 ng/mL in September 2010 and 32 ng/mL in August 2011. Currently, his PSA level is 52 ng/mL. Question 5: What treatment options do you suggest and recommend at this point? Appendix: Zoledronic acid was approved for metastatic bone tumor in April 2006, and docetaxel was approved for CRPC in August 2008 in Japan. However, none of cabazitaxel, abiraterone or sipuleucel-T has been approved yet. Marcus L Quek M.D., F.A.C.S. Department of Urology, Loyola University Stritch School of Medicine, Maywood, IL, USA The therapeutic considerations for castration-resistant prostate cancer (CRPC) have expanded greatly. The present case highlights a typical progression through the treated natural history of advanced prostate cancer, and provides an opportunity to consider an evidence-based algorithm for the use of these agents. For those on combined androgen blockade, anti-androgen withdrawal (AAW) can offer prostate-specific antigen (PSA) responses in 30–35%. AAW has not shown any clear survival benefit. The luteinizing hormone-releasing hormone agonist should be continued throughout the course, despite progression/addition of other treatments. Alternative hormonal therapies (ketoconazole, estrogens) might be considered in those with a rising PSA without clinical evidence of disease. Early consideration of bone-targeted agents (denosumab) should be considered to reduce/delay skeletal related events (SRE), which are often the source of great morbidity. Although estramustine and mitoxantrone provided a palliative effect, these agents did not improve survival. Data from clinical trials (TAX327, SWOG 9916) established docetaxel as the first agent to actually improve survival. With the approval of sipuleucel-T in the USA, consideration of this autologous vaccine therapy might be given to the asymptomatic patient with early CRPC before docetaxel. The most emergent of SRE is acute spinal cord compression. Steroids should be administered and imaging (magnetic resonance imaging) of the entire spine carried out to localize the involved region and identify impending fractures. Emergent consultation from neurosurgery and radiation oncology should be obtained with immediate radiotherapy given if surgical decompression/stabilization is not indicated. Denosumab is indicated for all patients with CRPC + bone metastases, unless contraindicated. For those that show clinical progression despite secondary hormonal manipulations, primary consideration should be given to docetaxel + prednisone. The survival benefit for docetaxel was small, but significant, compared with mitoxantrone. Until 2010, mitoxantrone was considered the de facto chemotherapy agent for patients progressing despite docetaxel. Studies have suggested limited activity and increased toxicity in this setting, with response rates of 9–20%. With the approval of cabazitaxel and abiraterone, these agents have become the standard treatment in the post-docetaxel scenario in the USA. Hiroji Uemura M.D., Ph.D. Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan Answer 1: At this point, I immediately switch bicalutamide to flutamide. For at least 3 months, I observe fluctuating PSA level after changing drug. When PSA increases over 2.0 ng/mL after flutamide administration, I stop it to confirm the occurrence of anti-androgen withdrawal syndrome. As for hormonal therapy, luteinizing hormone-releasing hormone (LHRH) agonist is continued all the way. Answer 2: I treat the patient with a low dose of dexamethasone (0.5 or 1.0 mg/body). Alternatively, if the patient does not have any cardiovascular disease, I treat him with estramustine or prosexol to expect its antitumor effect by estradiol. Furthermore, I treat him with angiotensin II receptor blocker (ARB) if the patient has hypertension. Comment: We have reported the potential of ARB as novel therapeutic agents for castration-resistant prostate cancer (CRPC; Uemura et al., Mol. Cancer. Ther. 2003). ARB treatment with candesartan decreased PSA levels by one-third in CRPC patients (Uemura et al., Int. J. Clin. Oncol. 2005). The mean time to PSA progression in responders after the start of ARB treatment was 8.3 months. Half of the patients treated with ARB showed an improvement in performance status (PS) after starting the study regardless of multiple metastases involving bone and lymph nodes. They did not require higher doses of opioid analgesics, or required only a minimal dose. We experienced some cases in which the PSA response was delayed for several months after starting ARB treatment. Thus, we expect that the administered dose of ARB was too low to overcome aggressive multiple metastases. Furthermore, a possible cause of the delayed PSA decline after treatment is thought to be that an ARB functions as a molecular targeting or cytostatic agent at many targeted points of signal transduction through membrane receptors. Answer 3: I ask a radiologist to carry out external beam radiation therapy (EBRT) focusing on Th6 and Th8 bone metastases. Simultan