Cancer Science: Open Access

Full Text

Research Article

Permanent Prostate Brachytherapy for Localized High-risk Prostate Cancer Patients with Coronary Heart Disease: A 13-year Single-center Experience

Luo Yong, Li Mingchuan, Qi Hengzhi, Wei Nengbao, Zhao Jiahui, Cui Xinhao, Han Yili, Lin Yunhua, Hou Zhu, Jiang Yong-guang and Zhang Jiao

Correspondence Address :

Jiang Yong-guang
Department of Urology, Beijing Anzhen Hospital, Capital Medical University
Anzhenli Street, Chaoyang District, Beijing, 100029, PR. China
Email: jyganzhen@163.com
Zhang jiao
Anatomy and Cell biology, East Carolina University
Greenville, NC, USA, 27834
E-mail: zhangj15@ecu.edu

Received on: August 20, 2015, Accepted on: October 07, 2015, Published on: October 14, 2015

Citation: Luo Yong, Li Mingchuan, Qi Hengzhi, Wei Nengbao, Zhao Jiahui, Cui Xinhao, Han Yili, Lin Yunhua, Hou Zhu, Jiang Yong-guang, Zhang Jiao (2015). Permanent Prostate Brachytherapy for Localized High-risk Prostate Cancer Patients with Coronary Heart Disease: A 13- year Single-center Experience

Copyright: 2015 Zhang Jiao, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

  • Abstract

  • Fulltext

  • References

  • Tables & Figures

  • Download PDF

Objective: To investigate whether permanent prostate brachytherapy (PPB) improves survival outcomes in localized high-risk prostate cancer (PCa) patients with coronary heart disease (CHD) via ameliorating prostate-specific antigen (PSA) kinetics.
Material and methods: We retrospectively reviewed the entire patient database regarding the survival and PSA kinetics of 216 consecutive localized PCa patients with clinical CHD who were treated from January 2001 to July 2012 at the Urology Department of the Beijing Anzhen Hospital. Kaplan-Meier analysis was used to calculate cause-specific survival (CSS) and overall survival (OS), and survival predictor was determined by log-rank and Cox-regression analyses. Differences in PSA kinetics and survival rate were compared between maximal androgen blockade (MAB)-treated cases and MAB + PPB-treated cases.
Results: The median follow-up time was 44 (range: 7-165) months. Brachytherapy, PSA nadir, and declining PSA were closely associated with survival. Compared with MAB monotherapy, combination therapy of MAB + PPB significantly ameliorated PSA kinetics. Additionally, MAB + PPB significantly improved the 13-year survival rate compared with MAB monotherapy (CSS: 56% vs. 13%; OS: 33% vs. 4%).
Conclusions: Combining PPB and MAB significantly increased the survival rates of localized high-risk PCa patients with CHD. PSA nadir ≤ 1 ng/mL and a >90% PSA decrease were independent prognostic factors for both CSS and OS.
Keywords: Prostate cancer, Brachytherapy, PSA kinetics, Maximal androgen blockade, Coronary heart disease
Prostate cancer (PCa) is a common malignancy associated with high morbidity and mortality. Radical prostatectomy (RP), radical external beam radiation therapy (EBRT), and maximal androgen blockade (MAB) are always preferred approaches for localized high-risk PCa patients [1]. However, in patients suffering from severe coronary heart disease (CHD) who are not good candidates for RP or EBRT, MAB is a safer option, without possibilities of serious anesthesia complications. Although numerous studies demonstrated the utility of MAB, the survival outcome with MAB monotherapy is not entirely satisfactory. In recent years, it has become an important issue regarding how to establish recommended treatment schemes and improve survival outcomes in localized high-risk PCa patients with CHD.
Modern brachytherapy was first applied for PCa in the 1980s when transrectal ultrasound became available to plan and guide radioactive seed placement within the prostate. Because of excellent 15-year PSA outcomes [2], PPB has been routinely used either as monotherapy for patients with low-risk and low/intermediate-risk disease or in combination with EBRT for patients with higher risk disease [3]. A recent comprehensive literature reviewed screened 18,000 papers and included over 50,000 patients comparatively analyzed the PSA-free survival outcomes of localized PCa patients treated with different radical therapies [4], and the results suggested that PSA outcomes with brachytherapy are significantly superior to EBRT in low-risk patients and that brachytherapy monotherapy achieved equivalent PSA outcomes to a combination of EBRT and brachytherapy in patients with intermediate-risk disease. For high-risk patients, combination therapies involving EBRT and brachytherapy W/O androgen deprivation therapy (ADT) appear superior to more localized monotherapies, including seed implantation, RP, or EBRT. In view of the fact that most PCa patients, including those with high-risk disease, do not have metastatic disease at the time of treatment, local tumor eradication could produce excellent longterm PSA relapse-free outcomes [4-6]. Numerous researchers demonstrated that brachytherapy can achieve superior longterm PSA outcomes and is well tolerated by PCa patients over a long follow-up interval [7-10]. Unlike EBRT, high radiation doses delivered with brachytherapy produces much lower, usually undetectable PSA levels over long-term follow-up, suggesting an ablative effect of high radiation dose on prostate tissue [11,12].
Given the increasing incidence of cardiovascular disease, the number of PCa patients with comorbid severe CHD is also growing. Therefore, how to choose an appropriate treatment strategy for localized high-risk PCa patients with CHD and improve their survival prognosis became important challenges for urologists. In this study, we attempted to evaluate the clinical benefit of supplemental PPB by comparing the long-term survival outcomes and PSA kinetics in patients treated with MAB monotherapy, with a similar group of men who underwent combined MAB + PPB.
Material and methods
Ethics statement
The study has been approved by the Committee on the Ethics of Clinical Experiments of the Capital Medical University, and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Written informed consent was obtained from all individuals. Details that might disclose the identity of the subjects under study have been omitted.
Total 376 consecutive localized PCa patients with clinical CHD were treated at the Urology Department of Beijing Anzhen Hospital from January 1st 2001 to July 31st 2012. They were all previously diagnosed with CHD according to American Heart Association guidelines, with stenoses ≥ 70% in at least 1 major coronary artery, which was identified by coronary angiography and underwent successful PCI. Coronary artery stenting and postoperative treatment was performed according to the treatment guidelines for PCI. All the patients received one standardized drug treatment for at least 1 year, which included aspirin (100 mg) and clopidogrel (75 mg), and statin lipid-lowering drugs were taken in the long-term. The CHD duration after PCI was 1.6 -15 y (median: 5.8 y) for all these patients. For patients treated with brachytherapy additional to MAB, one month after seed implantation, pelvic CT scan were performed to detect the seed distribution within the prostate. If there is any unpredictable seed margin, a second implantation would be arranged. Follow-up for all the patients ended on December 31st, 2014. All patients were clinically diagnosed by concentration determination of serum PSA, transrectal prostate ultrasonography, pathological examination of puncture biopsy specimens or surgically removed specimens, radioisotope scan of bone, and computed tomography of the abdomen and pelvis.
Patient follow-up and data collection
Patients were monitored by serum PSA determinations every 3 months for the first year, every 6 months for the second year, and yearly thereafter. During follow-up intervals, we measured PSA kinetics, including PSA nadir, the time required for PSA to reach nadir, and the decrease in PSA. Additionally, PSA doubling time (PSADT) was calculated by natural log 2 divided by the slope of the relationship between the log of PSA and the time of PSA measurement for each patient [13]. The endpoints of the analysis were CSS and OS. The cause of death was determined for each deceased patient. Patients with metastatic PCa or castrationresistant disease without obvious metastases who died of any cause were classified as PCa-related death. All other deaths were attributed to the immediate cause of death.
Statistical analysis
Kaplan-Meier analysis was first performed to calculate the CSS and OS of the total cohort and by separate groups. Then treatment and PSA parameters were evaluated for their impact on CSS and OS by univariate log-rank analysis and multivariate Cox regression analysis. Furthermore, we compared PSA kinetics and survival rates between patients treated with MAB monotherapy and those who underwent MAB+PPB combination therapy. All PSA kinetics results are presented as mean+/-SD. PSA variables were compared using independent-sample t-tests. Categorical variables were compared with chi-square analyses. For all statistical tests, P≤0.05 were considered statistically significant.
Patients' characteristics
Among 376 patients, 216 presented with high-risk disease (PSA ≥20 ng/ml or Gleason Score ≥8 or clinical stage ≥T2c). A total of 89(41.2%) men received MAB monotherapy (group A), and 127 (58.8%) men underwent combination therapy with MAB and PPB (group B). For combined therapeutic approaches, the minimum peripheral dose was 145 Gy for I-125 exposure. And the median lengths of follow-up of the total cohort were 44 months (range: 7-165 months). Furthermore, Table 1 summarizes the detailed clinical characteristics of patients included in the analysis. The ages of patients in group A ranged from 54 to 83 years old (mean: 75.7 years old), while those in group B ranged from 51 to 83 years old (mean: 70.3 years old). The median lengths of follow-up were 38 months (range: 9-163 months) and 47 months (range: 7-165 months) in groups A and B, respectively.
Factors influencing survival prognosis
Table 2 shows the univariate and multivariate analyses for predictors of CSS and OS. The number of coronary stents, brachytherapy, PSA nadir, the time for PSA to decrease to nadir, and the decline in PSA were independent prognostic factors of CSS(P<0.05). Although the traditional prognostic factor of prostate volume was significant on univariate analysis, it was not significant on multivariate analysis (P=0.691). Age, MAB pattern, and PSADT were not significantly associated with CSS (P>0.05). Additionally, univariate analysis indicated that age, the number of coronary stents, brachytherapy, PSA nadir, PSADT, and the decline in PSA were all predictors for OS in localized highrisk PCa patients (P<0.05). Multivariate Cox regression analysis further identified brachytherapy, PSA nadir and decline in PSA as independent prognostic indicators for OS (P<0.05).
Effect of additional PPB on the PSA kinetics of MAB treated high-risk patients
Several recent studies reported that PSA kinetics are closely related to long-term survival outcomes of PCa patients [14-16]. In this study, we summarized that characteristics of PSA kinetics were influenced by PPB in localized high-risk PCa patients with CHD. The mean PSA nadir of patients treated with MAB monotherapy (group A) was 2.85+/-1.37ng/mL (range: 0.03-16.00 ng/mL), whereas the mean PSA nadir of patients treated with MAB+PPB combination therapy (group B) was 0.11 +/- 0.05 ng/mL (range: 0.00-1.78 ng/mL). The mean time of PSA decrease to nadir in groups A and B were 7.12 +/- 1.48 months (range: 3-15 months) and 3.66 +/- 1.29 months (range: 1-9 months), respectively.
Additionally, mean PSADTs were 10.48 +/- 3.17 months (range: 0.87-21.56 months) in group A and 16.72 +/- 5.43 months (range: 3.46-39.52 months) in group B. Finally, mean decreases in PSA were 82.29 +/- 1.21% (range: 73.61-88.25%) in group A and 97.86 +/- 0.65% (range: 91.31-99.89%) in group B. Our results demonstrated that PPB significantly improved PSA kinetics as shown in Figure 1. Specifically, PSA nadir and the decrease in PSA, both of which are important independent indicators for CSS and OS, were notably ameliorated by additional PPB.
Effect of additional PPB on the survival curves of MABtreated high-risk patients
As shown in Figure 2A, the OS of all patients rapidly decreased from 92% to 34% during the 6 years after treatment, then slowly declined to 21% during the last 7 years. Overall, the downward trend in group A was much swifter than that in group B. During the first 6 years of the follow-up period, the OS in group A fell from 92% to 12%, whereas the OS in group B decreased more gradually from 94% to 52%. At the end of follow-up, the OS in group A finally decreased to 4%, whereas the OS in group B still maintained around 33% (P < 0.01). Median survival was 12% in group A and 43% in group B (P < 0.01), respectively. Figure 2B shows that the CSS of all patients progressively decreased from 98% to 43%, and the CSS curve of group A dropped sharply from 98% to 13%, while that of group B declined from 98% to 56%. And the 13-year cumulative CSS is significantly different between these two groups (13% vs 56%, P < 0.01). Median survival was 38% in group A and 74% in group B (P < 0.01), respectively.
Based on these data, we concluded that the addition of PPB could significantly improve the OS and CSS of patients treated with MAB.
As it is known that MAB is a safe option for PCa patients with comorbidities that make them poor candidates for RP or EBRT [1]. But for patients suffering from severe coronary heart disease (CHD), the survival outcome with MAB monotherapy is not extensively investigated. In the other hand, permanent prostate brachytherapy (PPB) has recently emerged as a definitive treatment option in men with clinically localized prostate cancer. While some groups believe that all patients should receive adjuvant EBRT, it appears that those at low and intermediate risk may be treated successfully with an implant as monotherapy [7]. Therefore, in this single-center study, we investigate and present a 13-year follow-up outcomes from a complete data set of consecutively treated patients who have undergone MAB monotherapy, as compared with combined MAB + PPB, in order to evaluate whether the addition of PPB to an MAB regiment improved survival in PCa patients with CHD.
MAB is widely used as a monotherapy or as an adjuvant to EBRT, RP, or brachytherapy. In advanced PCa, MAB was found to significantly improve 5-year survival by about 2.9% compared to androgen deprivation therapy(ADT) alone, and there was no significant heterogeneity in treatment effect (MAB vs. ADT) with respect to age or disease stage [17].
Interstitial radiation therapy has always been used to treat clinically localized PCa, and most researchers believe that the 5-year PSA outcome of brachytherapy in low-risk patients is not statistically different with those who undergo RP or EBRT. In addition, intermediate- and high-risk patients treated with RP or EBRT may respond better than those treated by brachytherapy [18]. However, this view remains controversial. Polascik et al. reported that 7-year actuarial PSA progression-free survival following RP was remarkably higher than that of patients who underwent I-125 brachytherapy (97.8% vs 79%) [19,20] in patients with localized PCa. Therefore, Polascik et al. pointed out that brachytherapy should be cautiously recommended to patients with localized PCa. Sharkey and colleagues analyzed data from 1,707 PCa patients with T1 or T2 staging who were treated by either brachytherapy or RP. They concluded that the time to PSA-indicated recurrence was better controlled by brachytherapy than RP in intermediate (89% vs. 58%, P < 0.05) and high-risk (88% vs. 43%, P < 0.05) groups, but not in lowrisk groups (89% vs. 94%, P = 0.174) [21]. Moreover, Taira et al. reported data from 329 cases of high-risk PCa treated with brachytherapy + EBRT with a 10-year follow-up, which indicated that CSS in patients of Gleason 5 is significantly lower than that in non-Gleason 5 patients (90.3% vs. 98.1%, P = 0.011). However, there is no remarkable difference in biochemical relapse-free survival and OS between these two groups of patients [22].
In addition, Demanes et al. also reviewed data from 209 cases treated with brachytherapy + EBRT with a 10-year followup and observed that the OS and CSS rates were 79% and 97%, respectively. The PSA progression-free survival rates were 90%, 87%, and 69% for the low-, intermediate-, and high-risk groups, respectively [23]. Another study reported that compared to brachytherapy monotherapy, the combination strategy of brachytherapy + EBRT conferred a significant advantage in the 5-year biochemical relapse-free survival rate (80% vs. 59%, P < 0.01) despite the greater proportion of adverse disease factors in the EBRT group [24]. Collectively, the existing clinical research supports brachytherapy + EBRT as a proven treatment for all stages of localized PCa [25]. When additional hormonal therapy to brachytherapy, the 5-year actuarial freedom from biochemical relapse rate of PCa patients (stage T1b-T3b) improved from 54% to 79%. In intermediate-risk patients, the 4-year actuarial freedom from biochemical relapse rate was 94%. The addition of hormonal therapy could noticeably improve outcome in intermediate- to high-risk PCa patients treated with brachytherapy [26]. However, after retrospectively analyzing data from 1,668 cases, Ciezki et al. concluded that addition of ADT did not improve the 5-year biochemical relapse-free survival in low- and intermediate-risk patients treated by brachytherapy [27].
In the past, it was controversial whether PPB + hormonal therapy was an effective and safe option for PCa patients with CHD. Nanda and colleagues conducted series of studies about the relationship between the additions of neoadjuvant hormonal therapy to brachytherapy in PCa patients with comorbidities. They concluded that there was a significantly increased risk of all-cause mortality in men with congestive heart failure, myocardial infarction, diabetes mellitus, or hypertension compared with men  without comorbidities. In contrast, men with hypercholesterolemia had a similar risk of all-cause mortality when compared with men with no comorbidity [28]. Similarly, neoadjuvant hormonal therapy was not associated with an increased risk of all-cause mortality in radiation therapy-treated men with a single CHD risk factor after a median follow-up of 4.4 years. However, for radiation therapy-treated men with CHD-induced congestive heart failure or myocardial infarction, neoadjuvant hormonal therapy was significantly associated with an increased risk of all-cause mortality after 5.1 years of follow-up [29]. Subsequently, they accurately summarized that for men with no risk factors or at least a single risk factor for CHD, neoadjuvant hormonal therapy is associated with an increased risk of all-cause mortality in the setting of low-risk but not intermediate- or high-risk PCa. Given the widespread use of neoadjuvant hormonal therapy for prostate downsizing prior to brachytherapy, these findings warrant additional validation [30].
As to the limitation, patients in this study were treated at a single center, so the results may not be generalized to more diverse populations. In addition, patients were not stratified by CHD severity. A large, randomized, multi-center study that assesses PCa patients with different levels of CHD severity would provide additional evidence regarding the outcomes for this group of patients. In conclusion, combination MAB + PPB treatment is a preferred option for high-risk PCa patients with CHD, because it achieves  excellent survival outcomes and favorable PSA kinetics. Our results indicate that PSA nadir ≤1 ng/mL and a PSA decrease >90% are two independent prognostic factors for both CSS and OS.
This work was supported by National Natural Science Foundation of China (NO. 30700968).
Interest Statement
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

1. Mohan R, Schellhammer PF. Treatment options for localized prostate cancer. Am Fam Physician, 2011;84(4):413-420.
2. Sylvester JE, Grimm PD, Wong J, Galbreath RW, Merrick G, Blasko JC. Fifteen-year biochemical relapse-free survival, cause-specific survival,and overall survival following i(125) prostate brachytherapy in clinically localized prostate cancer: Seattle experience. Int J Radiat Oncol Biol Phys, 2011;81(2):376-381.
3. Davis BJ, Horwitz EM, Lee WR, Crook JM, Stock RG, Merrick GS, et al. American brachytherapy society consensus guidelines for transrectal ultrasound-guided permanent prostate brachytherapy. Brachytherapy, 2012;11(1):6-19.
4. Grimm P, Billiet I, Bostwick DG, Dicker AP, Frank S, Immerzeel J, et al. Comparative analysis of prostate-specific antigen free survival outcomes for patients with low, intermediate and high risk prostate cancer treatment by radical therapy. Results from the prostate cancer results study group. BJU Int, 2012;109(Supp 1):22-29.
5. Zelefsky MJ, Reuter VE, Fuks Z, Scardino P, Shippy A. Influence of local tumor control on distant metastases and cancer related mortality after external beam radiotherapy for prostate cancer. J Urol, 2008;179(4):1368-1373.
6. Martinez AA, Gonzalez J, Ye H, Ghilezan M, Shetty S, Kernen K, et al. Dose escalation improves cancer-related events at 10 years for intermediate- and high-risk prostate cancer patients treated with hypofractionated high-doserate boost and external beam radiotherapy. Int J Radiat Oncol Biol Phys, 2011;79(2):363-370.
7. Zelefsky MJ, Yamada Y, Pei X, Hunt M, Cohen G, Zhang Z, et al. Comparison of tumor control and toxicity outcomes of high-dose intensity-modulated radiotherapy and brachytherapy for patients with favorable risk prostate cancer. Urology, 2011;77(4):986-990.
8. Deutsch I, Zelefsky MJ, Zhang Z, Mo Q, Zaider M, Cohen G, et al. Comparison of PSA relapse-free survival in patients treated with ultra-high-dose IMRT versus combination HDR brachytherapy and IMRT. Brachytherapy, 2010;9(4):313-318.
9. Potters L, Morgenstern C, Calugaru E, Fearn P, Jassal A, Presser J, et al. 12- Year outcomes following permanent prostate brachytherapy in patients with clinically localized prostate cancer. J Urol, 2008;179(5 Suppl):S20-4.
10. Morris WJ, Keyes M, Palma D, Spadinger I, McKenzie MR, Agranovich A, et al. Population-based study of biochemical and survival outcomes after permanent 125I brachytherapy for low- and intermediate-risk prostate cancer. Urology, 2009;73(4): 860-865.
11. Stock RG, Klein TJ, Cesaretti JA, Stone NN. Prognostic significance of 5-year PSA value for predicting prostate cancer recurrence after brachytherapy alone and combined with hormonal therapy and/or external beam radiotherapy. Int J Radiat Oncol Biol Phys, 2009;74(3):753-758.
12. Aaltomaa SH, Kataja VV, Lahtinen T, Palmgren JE, Forsell T. Eight years experience of local prostate cancer treatment with permanent I125 seed brachytherapy--morbidity and outcome results. Radiother Oncol, 2009;91(2):213-216.
13. Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC. Natural history of progression after PSA elevation following radical prostatectomy. JAMA, 1999; 281(17):1591-1597.
14. Antonarakis ES, Zahurak ML, Lin J, Keizman D, Carducci MA, Eisenberger MA. Changes in PSA kinetics predict metastasis- free survival in men with PSA-recurrent prostate cancer treated with nonhormonal agents: combined analysis of 4 phase II trials. Cancer, 2012;118(6):1533-1542.
15. Robinson D, Sandblom G, Johansson R, Garmo H, Aus G, Hedlund PO, et al. PSA kinetics provide improved prediction of survival in metastatic hormone refractory prostate cancer. Urology, 2008;72(4):903-907.
16. Crook J, Gillan C, Yeung I, Austen L, McLean M, Lockwood G. PSA kinetics and PSA bounce following permanent seed prostate brachytherapy. Int J Radiat Oncol Biol Phys, 2007;69(2):426-433.
17. Prostate Cancer Trialists' Collaborative Group. Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials. Lancet, 2000;355(9214):1491-1498.
18. D'Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA, 1998;280(11):969-974.
19. Polascik TJ, Pound CR, DeWeese TL, Walsh PC. Comparison of radical prostatectomy and iodine 125 interstitial radiotherapy for the treatment of clinically localized prostate cancer: a 7-year biochemical (PSA) progression analysis. Urology, 1998;51(6):884-890.
20. Ragde H, Blasko JC, Grimm PD, Kenny GM, Sylvester JE, Hoak DC, et al. Interstitial iodine-125 radiation without adjuvant therapy in the treatment of clinically localized prostate carcinoma. Cancer, 1997;80(3):442-453.
21. Sharkey J, Cantor A, Solc Z, Huff W, Chovnick SD, Behar RJ, et al. 103Pd brachytherapy versus radical prostatectomy in patients with clinically localized prostate cancer: a 12-year experience from a single group practice. Brachytherapy, 2005;4(1):34-44.
22. Taira AV, Merrick GS, Galbreath RW, Butler WM, Lief JH, Adamovich E, et al. Long-term outcomes of prostate cancer patients with Gleason pattern 5 treated with combined brachytherapy and external beam radiotherapy. Brachytherapy, 2013;12(5): 408-414.
23. Demanes DJ, Rodriguez RR, Schour L, Brandt D, Altieri G. High-dose-rate intensity-modulated brachytherapy with external beam radiotherapy for prostate cancer: California endocurietherapy's 10-year results. Int J Radiat Oncol Biol Phys, 2005;61(5):1306-1316.
24. Jani AB, Feinstein JM, Pasciak R, Krengel S, Weichselbaum RR. Role of external beam radiotherapy with low-dose-rate brachytherapy in treatment of prostate cancer. Urology, 2006;67(5):1007-1011.
25. Matzkin H, Keren-Paz G, Mabjeesh NJ, Chen J. Combination therapy permanent interstitial brachytherapy and external beam radiotherapy for patients with localized prostate cancer. Acta Chir Iugosl, 2005;52(4):31-36.
26. Lee LN, Stock RG, Stone NN. Role of hormonal therapy in the management of intermediate-to high-risk prostate cancer treated with permanent radioactive seed implantation. Int J Radiat Oncol Biol Phys, 2002;52(2):444-452.
27. Ciezki JP, Klein EA, Angermeier K, Ulchaker J, Chehade N, Altman A, et al. A retrospective comparison of androgen deprivation (AD) vs. no AD among low-risk and intermediate-risk prostate cancer patients treated with brachytherapy, external beam radiotherapy, or radical prostatectomy. Int J Radiat Oncol Biol Phys, 2004;60(5):1347-1350.
28. Nanda A, Chen MH, Moran BJ, Braccioforte MH, Dosoretz D, Salenius S, et al. Neoadjuvant Hormonal Therapy Use and the Risk of Death in Men with Prostate Cancer Treated with Brachytherapy Who Have No or at Least a Single Risk Factor for Coronary Artery Disease. Eur Urol, 2014;65(1):177-185.
29. Nanda A, Chen MH, Braccioforte MH, Moran BJ, D'Amico AV. Hormonal therapy use for prostate cancer and mortality in men with coronary artery disease-induced congestive heart failure or myocardial infarction. JAMA, 2009;302(8):866-873.
30. Nanda A, Chen MH, Moran BJ, Braccioforte MH, D'Amico AV. Cardiovascular comorbidity and mortality in men with prostate cancer treated with brachytherapy-based radiation with or without hormonal therapy. Int J Radiat Oncol Biol Phys, 2013;85(5):e209-15.
Tables & Figures

Figure 1. Differences in PSA kinetics between cases treated by MAB monotherapy (group A) and MAB + PPB combination therapy (group B). (▲) indicates P < 0.05 and (▲▲) indicates P < 0.01. Abbreviation: PSA, prostate-specific antigen; MAB, maximal androgen blockade; PPB, permanent prostate brachytherapy.  

Figure 2. The survival outcomes of all patients, group A, and group B during the 13-year follow-up period are comparatively presented as OS (Figure 2A) and CSS (Figure 2B). Group A = MAB monotherapy, Group B = MAB + PPB combination therapy. Abbreviation: CSS, cause-specific survival; OS, overall survival; MAB, maximal androgen blockade; PPB, permanent prostate brachytherapy. 

Table 1. The clinical characteristics of localized high-risk PCa patients with CHD stratified by treatment strategy.

Table 2. Univariate and multivariate analyses for CSS and OS of localized high-risk PCa patients with CHD.
Download PDF