Perioperative complications of radical retropubic prostatectomy in patients with locally advanced prostate cancer： a comparison with clinically localized prostate cancer

Radical prostatectomy （RP） continues to be an effective surgical therapy for prostate carcinoma, particularly for organ-confined prostate cancer （PCa）. Recently, RP has also been used in the treatment of locally advanced prostate cancer. However, little research has been performed to elucidate the perioperative complications associated with RP in patients with clinically localized or locally advanced PCa. We sought to analyse the incidence of complications in these two groups after radical retropubic prostatectomy （RRP）. From June 2002 to July 2010, we reviewed 379 PCa patients who underwent RRP in our hospital. Among these cases, 196 had clinically localized PCa （Tla-T2c group 1）, and 183 had locally advanced PCa （ ≥ T3,： group 2）. The overall complication incidence was 21.9%, which was lower than other studies have reported. Perioperative complications in patients with locally advanced PCa mirror those in patients with clinically localized PCa （26.2% vs. 17.8%, P=0.91）. Our results showed that perioperative complications could not be regarded as a factor to consider in regarding RP in patients with cT3 or greater.

The Impact of Variation in Bladder Volume on the Doses of Target and Organ-at-Risk in Intensity-Modulated Radiation Therapy for Localized Prostate Cancer

Intensity-modulated radiation therapy (IMRT) has become the mainstay of treatment for localized prostate cancer. In IMRT, minimizing differences between the conditions used during planning CT and daily treatment is important to prevent adverse events in normal tissues. In the present study, we evaluated the impact of variation in bladder volume on the doses to various organs. A total of 35 patients underwent definitive radiotherapy at Saitama Medical Center. A Light Speed RT16 (GE Healthcare) was used for planning and to obtain examination CT images. Such images were acquired after 4 - 6 days of planning CT image acquisition. The IMRT plans were optimized using the planning CT data to satisfy the dose constraints set by our in-house protocols for the PTV and the OARs. The dose distributions were then re-calculated using the same IMRT beams, and checked on examination CT images. It was clear that bladder volume affected the doses to certain organs. We focused on the prostate, bladder, rectum, small bowel, and large bowel. Regression coefficients were calculated for variables that correlated strongly with bladder volume (p < 0.05). We found that variation in bladder volume [cm3] predicted deviations in the bladder V70Gy, V50Gy, and V30Gy [%];the maximum dose to the small bowel [cGy];and the maximum dose to the large bowel [cGy]. The regression coefficients were -0.065, -0.125, -0.180, -10.22, and -9.831, respectively. We evaluated the impacts of such variation on organ doses. These may be helpful when checking a patient’s bladder volume before daily IMRT for localized prostate cancer.

Malignant field expression signatures in biopsy samples at diagnosis predict the likelihood of lethal disease in patients with localized prostate cancer

Aim:Overtreatment of early-stage low-risk prostate cancer patients represents a significant problem in disease management and has significant socio-economic implications.Changes in prostate cancer screening and treatment practices in the United States have been associated with the recent decline in overall incidence and concomitant significant increase of the annual incidence of metastatic prostate cancer has been documented.Therefore,development of genetic and molecular markers of clinically significant disease in patients diagnosed with low grade localized prostate cancer would have a major impact in disease management.Methods:Identification of gene expression signatures(GES)associated with lethal prostate cancer has been performed using microarray analyses of biopsy specimens obtained at the time of diagnosis from 281 patients with Gleason 6(G6)and G7 tumors in a Swedish watchful waiting cohort with up to 30 years follow-up.The performance of GES has been validated in independent cohort of 568 prostate cancer patients of the Cancer Genome Anatomy Project Prostate Cancer database.Results:GES c omprising 98 genes identified 89%and 100%of all death events 4 years after diagnosis in G7 and G6 patients,respectively.At 6 years follow-up,83%and 100%of all deaths events were captured in G7 and G6 patients,respectively.Remarkably,the 98-gene signature appears to perform successfully in patients stratification with as little as 2%of cancer cells in a specimen,strongly indicating that it captures a malignant field effect in human prostates harboring cancer cells of different degrees of aggressiveness.In G6 and G7 tumors from prostate cancer patients of age 65 or younger,GES identified 86%of all death events during the entire follow-up period.In G6 and G7 tumors from prostate cancer patients of age 70 or younger,GES identified 90%of all death events 6 years after diagnosis.Conclusion:Classification performance of the reported in this study 98-genes GES of lethal prostate cancer appeared suitable to meet design and feasibility requirements of a prospective 4 to 6 years clinical trial,which is essential for regulatory approval of diagnostic and prognostic tests in clinical setting.Prospectively validated GES of lethal PC in biopsy specimens of G6 and G7 tumors will help physicians to identify,at the time of diagnosis,patients who should be considered for exclusion from active surveillance programs and who would most likely benefit from immediate curative interventions.

The role of radiotherapy in localised and locally advanced prostate cancer

For a patient suffering from non-metastatic prostate cancer,the individualized recommendation of radiotherapy has to be the fruit of a multidisciplinary approach in the context of a Tumor Board,to be explained carefully to the patient to obtain his informed consent.External beam radiotherapy is now delivered by intensity modulated radiotherapy,considered as the gold standard.From a radiotherapy perspective,low-risk localized prostate cancer is treated by image guided intensity modulated radiotherapy,or brachytherapy if patients meet the required eligibility criteria.Intermediate-risk patients may benefit from intensity modulated radiotherapy combined with 4e6 months of androgen deprivation therapy;intensity modulated radiotherapy alone or combined with brachytherapy can be offered to patients unsuitable for androgen deprivation therapy due to co-morbidities or unwilling to accept it to preserve their sexual health.High-risk prostate cancer,i.e.high-risk localized and locally advanced prostate cancer,requires intensity modulated radiotherapy with long-term(≥2 years)androgen deprivation therapy with luteinizing hormone releasing hormone agonists.Post-operative irradiation,either immediate or early deferred,is proposed to patients classified as pT3pN0,based on surgical margins,prostate-specific antigen values and quality of life.Whatever the techniques and their degree of sophistication,quality assurance plays a major role in the management of radiotherapy,requiring the involvement of physicians,physicists,dosimetrists,radiation technologists and computer scientists.The patients must be informed about the potential morbidity of radiotherapy and androgen deprivation therapy and followed regularly during and after treatment for tertiary prevention and evaluation.A close cooperation is needed with general practitioners and specialists to prevent and mitigate side effects and maintain quality of life.

Long-term effectiveness of luteinizing hormone-releasing hormone agonist or antiandrogen monotherapy in elderly men with localizect prostate cancer （T1-2） ： a retrospective study

Aim： To evaluate the long-term effectiveness, side effects and compliance rates of two types of drugs （luteinizing hormone-releasing hormone [LHRH] agonist and antiandrogen） that were used individually to treat patients with localized prostate cancer （T1-2） at our institution. Methods： Ninety-seven patients who were diagnosed in the period from April 1997 to January 2000 as having clinically localized prostate cancer （T1-2） received either LHRH agonist （leuprolide acetate 7.5 mg/month） monotherapy （group 1, n = 62） or antiandrogen monotherapy （group 2, n = 35; 18 received bicalutamide 50 mg q.d., 13 received nilutamide 150 mg t.i.d, and 4 received flutamide 250 mg t.i.d.）. The mean age in both groups was 76 years. Results： The mean follow-up time was （50.8 ±8.5） months in group 1 and （43.1 ± 2.2） months in group 2. Prostate-specific antigen （PSA） levels rose in only 1 of the 62 patients （1.6%） in group 1, and in 20 of the 35 patients （57.1%） in group 2. In group 2, 10 of the 20 patients （50 %） with increasing PSA levels were treated with LHRH salvage therapy, and eight （80%） responded. Hot flashes （54.8%） and lethargy （41.9%） were the most common side effects in group 1. In contrast, nipple-tenderness （40%） and light-dark adaptation （17.1%） were more often seen in group 2. Only 1 of the 62 patients （1.6%） in group 1 switched to another medication because of adverse side effects; whereas 8 of the 35 patients （22.9%） in group 2 did so. Conclusion： Unlike antiandrogen monotherapy, LHRH agonist monotherapy provided long-term durable control of localized prostate cancer （T1-2）. It can also be an effective treatment option for patients whose disease failed to respond to antiandrogen monotherapy. The limitations of our study are the lack of health outcomes analysis and a small sample size.

Randomized controlled trial comparing open anterograde anatomic radical retropubic prostatectomy with retrograde technique

Objective:Radical prostatectomy is the recommended treatment for localized prostate cancer;however,it is an invasive procedure that can leave serious morbidity.Robot-assisted radical prostatectomy was introduced with the aim of reducing postoperative morbidity and facilitating rapid recovery compared to the traditional Walsh’s open radical retropubic prostatectomy.Therefore,a protocol was developed to perform an open prostatectomy comparable to that performed by robotics,but without involving novel instrumentation.Methods:A total of 220 patients diagnosed with localized prostate cancer underwent radical prostatectomy.They were divided into two groups:anterograde technique(115 patients)and the retrograde method(105 patients).The study outcomes were observed 3 months after surgery.Results:No differences were found in terms of surgical time,hospital stay,and suction drainage.However,reduced bleeding was observed in the anterograde technique(p=0.0003),with rapid anastomosis duration(p=0.005).Among the patients,60.9% undergoing the anterograde technique were continent 3 months after surgery compared to 42.9%treated by the retrograde method(p=0.007).Additionally,fewer complications in terms of the number(p=0.007)and severity(p=0.0006)were observed in the anterograde technique.Conclusion:The anterograde method displayed increased efficiency in reducing complications,compared to the retrograde technique.

Outcomes of locally advanced prostate cancer:a single institution study of 209 patients in Japan

Aim： To investigate the outcomes for Asian populations with locally advanced/clinical stage Ⅲ prostate cancer （PCa） treated with currently prevailing modalities. Methods： We reviewed the record of 209 patients with clinical stage Ⅲ PCa, who were treated at Niigata Cancer Center Hospital between 1992 and 2003. Treatment options included hormone therapy-combined radical prostatectomy （RP＋HT）, hormone therapy-combined external beam irradiation （EBRT＋HT） and primary hormone therapy （PHT）. Results： The 5- and 10-year overall survival rates were 80.3% and 46.1% in all cohorts, respectively. The survival rates were 87.3% and 66.5% in the RP＋HT group, 94.9% and 70.0% in the EBRT＋HT group and 66.1% and 17.2% in the PHT group, respectively. A significant survival advantage was found in the EBRT＋HT group compared with that in the PHT group （P 〈 0.0001）. Also, the RP＋HT group had better survival than the PHT group （P = 0.0107）. The 5- and 10-year disease-specific survival rates for all cases were 92.5% and 80.0%, respectively. They were 93.8% and 71.4% in the RP＋HT group, 96.6% and 93.6% in the EBRT＋HT group and 88.6% and 62.3% in the PHT group, respectively. A survival advantage was found in the EBRT＋HT group compared with the PHT group （P = 0.029）. No significant difference was found in disease-specific survival between the EBRT＋HT and RP＋HT groups or between the RP＋HT and PHT groups. Condusion： Although our findings indicate that radiotherapy plus HT has a survival advantage in this stage of PCa, we recommend therapies that take into account the patients＇ social and medical conditions for Asian men with clinical stage Ⅲ PCa.

Value of MRI diffusion weighted imaging in localization of prostate cancer with whole-mount step section pathology

Objective To evaluate the value of MRI diffusion weighted imaging in localization of prostate cancer with whole-mount step section pathology. Methods We treated 36 patients using laparoscopic radical prostatectomy from Oct. 2009 to Jun. 2010. Patients who did not have an MRL /DWI examination or a surgical history of pros-

Estrogen receptor （α and β） but not androgen receptor expression is correlated with recurrence, progression and survival in post prostatectomy T3NOMO locally advanced prostate cancer in an urban Greek population

The objective of this study was to evaluate the expression of estrogen receptors （ER（（α ） and ER（β）） and androgen receptors （ARs） as prognostic factors for biochemical recurrence, disease progression and survival in patients with pT3NOMO prostate cancer （PCa） in an urban Greek population. A total of 100 consecutive patients with pT3NOMO PCa treated with radical prostatectomy participated in the study. The mean age and follow-up were 64.2 and 6 years, respectively. The HSCORE was used for semi-quantitative analysis of the immunoreactivity of the receptors. The prognostic value of the ER（（α） and ER（β） and AR was assessed in terms of recurrence, progression, and survival. AR expression was not associated with any of the above parameters; however, both ERs correlated with the prognosis. A univariate Cox regression analysis showed that ER（α） positive staining was significantly associated with a greater hazard for all outcomes. Increased ER（β） staining was significantly associated with a lower hazard for all outcomes in the univariate analysis. When both ER HSCORES were used for the analysis, it was found that patients with high ER（α） or low ER（β） HSCORES compared with patients with negatively stained ER（α） and 〉1.7 hSCORE ER（β） had 6.03, 10.93, and 10.53 times greater hazard for biochemical disease recurrence, progression of disease and death, respectively. Multiple Cox proportional hazard analyses showed that the age, preoperative prostate specific antigen, Gleason score and ERs were independent predictors of all outcomes. ER expression is an important prognosticator after radical prostatectomy in patients with pT3NOMO PCa. By contrast, AR expression has limited prognostic value.