Performance characteristics of computed tomography in detecting lymph node metastases in contemporary patients with prostate cancer treated with extended pelvic lymph node dissection

Background

Computed tomography (CT) is a commonly used noninvasive procedure for prostate cancer (PCa) staging. All previous studies addressing the ability of CT scan to predict lymph node invasion (LNI) were based on historical patients treated with limited pelvic lymph node dissection (PLND).

Objective

Assess the value of CT in predicting LNI in contemporary PCa patients treated with extended PLND (ePLND).

Design, setting, and participants

We evaluated 1541 patients undergoing radical prostatectomy and ePLND between 2003 and 2010 at a single center. All patients were preoperatively staged using abdominopelvic CT scan. All lymph nodes with a short axis diameter ≥10 mm were considered suspicious for metastatic involvement.

Intervention

All patients underwent preoperative CT scan, radical retropubic prostatectomy, and ePLND, regardless of PCa features at diagnosis.

Measurements

The performance characteristics of CT scan were tested in the overall patient population, as well as according to the National Comprehensive Cancer Network (NCCN) classification and according to the risk of LNI derived from a nomogram developed on an ePLND series. Logistic regression models tested the relationship between CT scan findings and LNI. Discrimination accuracy was quantified with the area under the curve.

Results and limitations

Overall, a CT scan that suggested LNI was found in 73 patients (4.7%). Of them, only 24 patients (32.8%) had histologically proven LNI at ePLND. Overall, sensitivity, specificity, and accuracy of CT scan were 13%, 96.0%, and 54.6%, respectively. In patients with low-, intermediate-, or high-risk PCa according to NCCN classification, sensitivity was 8.3%, 96.3%, and 52.3%, respectively; specificity was 3.6%, 97.3%, and 50.5%, respectively; and accuracy was 17.9%, 94.3%, and 56.1%, respectively. Similarly, in patients with a nomogram-derived LNI risk ≥50%, sensitivity, specificity, and accuracy were only 23.9%, 94.7%, and 59.3%, respectively. At multivariable analyses, inclusion of CT scan findings did not improve the accuracy of LNI prediction (81.4% compared with 81.3%; p = 0.8). Lack of a central scan review represents the main limitation of our study.

Conclusions

In contemporary patients with PCa, the accuracy of CT scan as a preoperative nodal-staging procedure is poor, even in patients with high LNI risk. Therefore, the need for and the extent of PLND should not be based on the results obtained by CT scan.     

Low risk prostate cancer in men under age 65: the case for definitive treatment

The management of low risk prostate cancer, defined as Gleason’s sum ≤6, PSA <10 ng/ml, and clinical stage T1c to T2a, remains controversial. There is substantiating evidence to suggest that a subset of early stage, low risk cancers can cause significant patient morbidity and death in the long term. Studies have shown that the natural history of untreated prostate cancer is to progress, particularly after 15 years of followup. The majority of men seeking definitive surgical treatment in contemporary series fall within 55 to 65 years of age and are expected to enjoy an overall life expectancy ranging from about 15 to 30 years, placing these men at long-term risk for disease progression and prostate cancer-specific death if managed expectantly. During the past 2 decades, refinements in surgical technique and in the delivery of external beam radiation have resulted in excellent long-term cancer control and favorable quality of life outcomes following treatment. Active surveillance with selective delayed intervention assumes that an individual’s cancer will not progress outside the window of curability during the surveillance period, that markers for disease progression are reliable, and that patients are compliant. Until we understand better the long-term natural history of untreated prostate cancer, have more reliable and accurate markers to detect disease progression with certainty, and can risk stratify more precisely the subgroup of men with low risk cancers who will eventually succumb to their disease, early definitive therapy seems prudent.     

人组织激肽释放酶6在前列腺癌中的表达和意义

目的初步探讨人组织激肽释放酶6(Kallikrein 6,KLK6)在前列腺癌中的表达和意义。方法搜集徐州医学附属医院泌尿外科2010-06—2013-10行前列腺根治手术患者组织标本共65例,其中40例前列腺癌(Prostate Cancer,PCa),25例为前列腺增生组织,应用免疫组织化学两步法,检测组织中KLK6蛋白表达情况。结果 PCa患者组织中KLK6阳性表达率为75%,前列腺增生(Hyperplasia of prostate,BPH)组织KLK6阳性表达率为24%,两者比较癌组织显著高于增生组织(P0.01);前列腺癌中低危患者KLK6阳性表达率为58.25%,中高危患者为75%,两者比较中高危患者明显高于低危患者(P0.05)。结论 KLK6在前列腺癌组织表达明显高于前列腺增生,中高危患者明显高于低危患者,KLK6基因可能在前列腺癌诊断和预后判断中存在一定价值。     

Mitochondrial DNA in serum of patients with prostate cancer: a predictor of biochemical recurrence after prostatectomy

OBJECTIVE

To investigate the role of circulating mitochondrial DNA (mtDNA) in patients with localized prostate cancer, as recent reports show that patients with advanced cancer have increased levels of mtDNA.

PATIENTS AND METHODS

DNA was isolated from the serum of 100 patients with prostate cancer and 18 with benign prostate hyperplasia (BPH). A quantitative real‐time polymerase chain reaction was used to amplify 79 bp and 230 bp fragments of the mitochondrial 16s‐RNA gene, the short fragment representing total mtDNA, including mtDNA truncated by apoptosis, and the long fragment representing mostly mtDNA from other cell death entities. mtDNA integrity was defined as the ratio of long to short mtDNA fragments.

RESULTS

The short and long mtDNA levels, and mtDNA integrity, were similar in patients with BPH and cancer (P = 0.940, 0.211 and 0.441, respectively), and were not correlated with clinical or pathological variables, e.g. age, prostate‐specific antigen (PSA) level, cT stage, pT stage, seminal vesicle infiltration, lymph node invasion, or Gleason score (P = 0.075 to 0.961). However, patients with high levels of short mtDNA (>75th percentile) had a greater risk of PSA progression and this variable was the strongest predictor of PSA recurrence in a multivariate Cox analysis (P = 0.023; hazard ratio 0.31; 95% confidence interval 0.113–0.851).

CONCLUSION

Circulating mtDNA levels did not distinguish between patients with prostate cancer or BPH. However, there was a significant increase in short mtDNA fragments in patients with early PSA recurrence after radical prostatectomy.     

Pretreatment multiparametric MRI is independently associated with biochemical outcome in men treated with radiation therapy for prostate cancer

Purpose

The purpose of this study was to investigate the utility of pre-treatment multiparametric magnetic resonance imaging (mpMRI) in a modern cohort of intermediate and high-risk prostate cancer patients treated with primary radiotherapy.

Actual change in anxiety and depression among Australian men with prostate cancer

Background

The clinical significance of anxiety and depression in prostate cancer patients remains largely unclear. In particular, the importance of somatic symptoms and their change over time has been largely unaddressed in spite of their immediate relevance to an understanding of these psychosocial aspects of prostate cancer and its treatment.

Methods

Self-reports of current and previous states of anxiety and depression were collected from 183 Australian men with prostate cancer between 9 and 71 months (average = 1 year 10 months) after initial diagnosis. An ‘Actual Change’ methodology was used to overcome the effects of extraneous sources of invalidity. Statistical tests of the total scores and specific item-changes over time were conducted.

Results

Mean anxiety and depression levels reduced from time of diagnosis to time of the survey, with the most prominent changes being associated with reductions in psychomotor agitation, weakness, fatigue and pessimism. Clinically significant anxiety reduced from about 20% to 12%; clinical depression reduced from about 24% to 12.5%.

Conclusion

While many prostate patients reported anxiety and depression at the time of receiving their diagnosis, about half of those for whom these disorders were of clinical significance had lowered their symptomatology 2 years later. Assessment of somatic symptoms remains a key indicator of depression and anxiety among this patient group.     

SPECT与PSA联合检测诊断前列腺癌的临床意义

目的：探讨放射性核素骨显像与血清前列腺特异抗原联合检测在前列腺癌诊断中的临床意义。方法;采用单光子发射型计算机断层摄影术骨显像及血清ＰＳＡ浓度检测诊断ＰＣａ患者６３例。结果：６３例ＰＣａ患者中,血清ＰＳＡ测定阳性率为９６．８３％,ＳＰＥＣＴ骨显像转移率为５７．１４％。结论：ＳＰＥＣＴ骨显像与血清ＰＳＡ浓度联合检测对于ＰＣａ患者的临床诊断及治疗具有重要的指导意义。     

Mental health outcomes in elderly men with prostate cancer

ObjectiveTo examine the burden of mental health issues (MHI), namely anxiety, depressive disorders, and suicide, in a population-based cohort of older men with localized prostate cancer and to evaluate associations with primary treatment modality.Patients and methodsA total of 50,856 men, who were 65 years of age or older with clinically localized prostate cancer diagnosed between 1992 and 2005 and without a diagnosis of mental illness at baseline, were abstracted from the Surveillance, Epidemiology, and End Results–Medicare database. The primary outcome of interest was the development of MHI (anxiety, major depressive disorder, depressive disorder not elsewhere classified, neurotic depression, adjustment disorder with depressed mood, and suicide) after the diagnosis of prostate cancer.ResultsA total of 10,389 men (20.4%) developed MHI during the study period. Independent risk factors for MHI included age≥75 years (hazard ratio [HR] = 1.29); higher comorbidity (Charlson comorbidity index≥3, HR = 1.63); rural hospital location (HR = 1.14); being single, divorced, or widowed (HR = 1.12); later year of diagnosis (HR = 1.05); and urinary incontinence (HR = 1.47). Black race (HR = 0.79), very high-income status (HR = 0.87), and definitive treatment (radical prostatectomy [RP], HR = 0.79; radiotherapy [RT], HR= 0.85, all P<0.001) predicted a lower risk of MHI. The rates of MHI at 10 years were 29.7%, 29.0%, and 22.6% in men undergoing watchful waiting (WW), RT, and RP, respectively.ConclusionOlder men with localized prostate cancer had a significant burden of MHI. Men treated with RP or RT were at a lower risk of developing MHI, compared with those undergoing WW, with median time to development of MHI being significantly greater in those undergoing RP compared with those undergoing RT or WW.     

Tumor volume,surgical margin,and the risk of biochemical recurrence in men with organ-confined prostate cancer

ObjectivesWe proposed to investigate predictors of biochemical recurrence (BCR) in pT2 prostate cancer by identifying the interrelationship between the tumor volume and surgical margin status, and their impact on recurrence.Materials and methodsClinical, pathologic, and follow-up data of 404 consecutive patients who were treated with radical prostatectomy alone and were diagnosed as pT2 prostate cancer in our institution were reviewed. Percent tumor volume (PTV) was estimated from the cancer distribution map, and the surgical margin status was reviewed by a single pathologist (JYR). Clinicopathologic variables were analyzed with respect to the risk of BCR.Results and limitationsRecurrence was observed in 39 (9.7%) patients at a mean of 28.9 (5–47) months. Preoperative PSA, biopsy Gleason score, surgical Gleason score, PTV, and surgical margin status were significantly related to BCR in univariate analysis; in multivariate analysis, PTV (P < 0.001) and surgical Gleason score (P = 0.021) were independent predictors of BCR. PTV was also an independent determinant of positive surgical margin (P = 0.035, HR 1.026, 95% CI 1.002–1.050). By combining the 2 predictors 5-year recurrence-free survivals for PTV ≤ 14.5% and surgical Gleason score ≤ 7, PTV >14.5% or surgical Gleason score > 7, and PTV > 14.5% and surgical Gleason score > 7 were 97.5%, 88.7%, and 44.5%, respectively (log-rank test, P < 0.01). Retrospective study nature, use of PTV instead of actual volume, and intermediate follow-up length are the main limitations of the study.ConclusionsIn men with pT2 prostate cancer, percent tumor volume and the surgical Gleason score were independently prognostic of BCR and by combining the 2 factors, risk of BCR could be significantly stratified. Tumor volume further determined surgical margin status undermining its prognostic value as an independent variable.     

The extent of pelvic lymph node dissection correlates with the biochemical recurrence rate in patients with intermediate- and high-risk prostate cancer

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Pelvic lymph‐node dissection during radical prostatectomy for prostate cancer is certainly a fundamental staging procedure but its therapeutic role is yet under debate. This retrospective study suggests that, in patients with intermediate‐ and high‐risk of prostate cancer, the greater the number of lymph‐nodes removed, the lower the risk of biochemical relapse, even in the presence of 1 or 2 lymph‐node metastasis. However, the Will Rogers phenomenon must be considered due to the retrospective nature of the present study.

OBJECTIVE

• ? To assess the impact of pelvic lymph node dissection (PLND) and of the number of lymph nodes (LNs) retrieved during radical prostatectomy (RP) on biochemical relapse (BCR) in pNX/0/1 patients with prostate cancer according to the clinical risk of lymph node invasion (LNI).

PATIENTS AND METHODS

• ? We evaluated 872 pT2‐4 NX/0/1 consecutive patients submitted to RP between October 1995 and June 2009, with the following inclusion criteria: (i) a follow‐up period ≥12 months; (ii) the avoidance of neoadjuvant hormonal therapy or adjuvant hormonal and/or adjuvant radiotherapy; (iii) the availability of complete follow‐up data; (iv) no pathological T0 disease; (v) complete data regarding the clinical stage and Gleason score (Gs), the preoperative prostate‐specific antigen (PSA) level and the pathological stage.
• ? The patients were stratified as having low risk (cT1a‐T2a and cGs ≤6 and PSA level < 10 ng/mL), intermediate risk (cT2b‐T2c or cGs = 7 or PSA level = 10–19.9) or high risk of LNI (cT3 or cGs = 8–10 or PSA level ≥ 20).
• ? The 872 patients were divided into two LN groups according to the number of LNs retrieved: group 1 had no LN or one to nine LNs removed; group 2 had 10 or more LNs.
• ? The variables analysed were LN group, age, PSA level, clinical and pathological stage and Gs, surgical margin status, LN status and number of LN metastases; the primary endpoint was the BCR‐free survival.

RESULTS

• ? The mean follow‐up was 55.8 months.
• ? Of all the patients, 305 (35%) were pNx and 567 (65.0%) were pN0/1.
• ? Of the 567 patients submitted to PLND, the mean number of LNs obtained was 10.9, and 49 (8.6%) were pN1.
• ? In the 402 patients at low risk of LNI, LN group was not a significant predictor of BCR at univariate analysis, while in the 470 patients at intermediate and high risk of LNI, patients with ≥10 LNs removed had a significantly lower BCR‐free survival at univariate and multivariate analysis.

CONCLUSION

• ? In our study population, a more extensive PLND positively affects the BCR‐free survival regardless of the nodal status in intermediate‐ and high‐risk prostate cancer.

     

Prediction of prostate cancer risk: the role of prostate volume and digital rectal examination in the ERSPC risk calculators

Background

The European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculators (RCs) are validated tools for prostate cancer (PCa) risk assessment and include prostate volume (PV) data from transrectal ultrasound (TRUS).

Objective

Develop and validate an RC based on digital rectal examination (DRE) that circumvents the need for TRUS but still includes information on PV.

Design, setting, and participants

For development of the DRE-based RC, we studied the original ERSPC Rotterdam RC population including 3624 men (885 PCa cases) and 2896 men (547 PCa cases) detected at first and repeat screening 4 yr later, respectively. A validation cohort consisted of 322 men, screened in 2010-2011 as participants in ERSPC Rotterdam.

Measurements

Data on TRUS-assessed PV in the development cohorts were re-coded into three categories (25, 40, and 60 cm³) to assess the loss of information by categorization of volume information. New RCs including PSA, DRE, and PV categories (DRE-based RC) were developed for men with and without a previous negative biopsy to predict overall and clinically significant PCa (high-grade [HG] PCa) defined as T stage >T2b and/or Gleason score ≥7. Predictive accuracy was quantified by the area under the receiver operating curve. We compared performance with the Prostate Cancer Prevention Trial (PCPT) RC in the validation study.

Results and limitations

Areas under the curve (AUC) of prostate-specific antigen (PSA) alone, PSA and DRE, the DRE-based RC, and the original ERSPC RC to predict PCa at initial biopsy were 0.69, 0.73, 0.77, and 0.79, respectively. The corresponding AUCs for predicting HG PCa were higher (0.74, 0.82, 0.85, and 0.86). Similar results were seen in men previously biopsied and in the validation cohort. The DRE-based RC outperformed the PCPT RC (AUC 0.69 vs 0.59; p = 0.0001) and a model based on PSA and DRE only (AUC 0.69 vs 0.63; p = 0.0075) in the relatively small validation cohort. Further validation is required.

Conclusions

An RC should contain volume estimates based either on TRUS or DRE. Replacing TRUS measurements by DRE estimates may enhance implementation in the daily practice of urologists and general practitioners.     

Targeted salvage lymphadenectomy in patients treated with radical prostatectomy with biochemical recurrence: complete biochemical response without adjuvant therapy in patients with low volume lymph node recurrence over a long-term follow-up

Background

Choline positron emission tomography/computed tomography (PET/CT) represents an option in restaging of prostate cancer patients with disease relapse after local treatment. The present study assess whether salvage resection of lymph node metastases detected on choline PET/CT imaging in prostate cancer patients with biochemical recurrence after radical prostatectomy can result in a long-term complete biochemical remission, without adjuvant therapy.

Methods

We analysed 13 patients with prostate specific antigen (PSA) recurrence (PSA median 1.64 ng/ml, range 0.5-9.55) after radical prostatectomy and suspicious lymph nodes (median 1; range 1–3) detected on [11C]choline and [18F]fluoroethylcholine PET/CT scans. An open salvage lymphadenectomy of positive lymph nodes in a PET/CT scan and nearby lymph nodes was carried out. We examined PSA outcome without adjuvant therapy; defined complete biochemical remission as PSA <0.01 ng/ml. Histological and PET/CT findings were compared.

Results

Ten of 11 patients with histologically confirmed lymph node metastases showed a PSA response. Three of ten patients with single lymph node metastases had a complete biochemical remission (median follow-up 72 months, range 31.0-83). In five cases with single lymph node metastasis PSA decreased <0.02 ng/ml. Histologically confirmed 13 of 16 metastasis suspicious lymph nodes. No lymph node metastases were detected in two patients. All of the additionally removed 30 lymph nodes were correctly negative.

Conclusions

This is the first confirmation of a complete biochemical remission after PET/CT guided secondary resection of a single lymph node metastasis in prostate cancer patients with biochemical recurrence after radical prostatectomy, over the long-term (>6.5 years), without adjuvant therapy. In order to improve these promising results, longer-term studies with more patients are required.     

Body mass index was associated with upstaging and upgrading in patients with low-risk prostate cancer who met the inclusion criteria for active surveillance

BackgroundObesity is associated with an increased risk of high-grade prostate cancer (PCa). The effect of body mass index (BMI) as a predictor of progression in men with low-risk PCa has been only poorly assessed.In this study, we evaluated the association of BMI with progression in patients with low-risk PCa who met the inclusion criteria for the active surveillance (AS) protocol.MethodsWe assessed 311 patients who underwent radical prostatectomy and were eligible for AS according to the following criteria: clinical stage T2a or less, prostate-specific antigen level<10 ng/ml, 2 or fewer cores involved with cancer, Gleason score ≤6 grade, and prostate-specific antigen density<0.2 ng/ml/cc. Reclassification was defined as upstaged (pathological stage>pT2) and upgraded (Gleason score ≥7; primary Gleason pattern 4) disease. Seminal vesicle invasion, positive lymph nodes, and tumor volume≥0.5 ml were also recorded.ResultsWe found that high BMI was significantly associated with upgrading, upstaging, and seminal vesicle invasion, whereas it was not associated with positive lymph nodes or large tumor volume. At multivariate analysis, 1 unit increase of BMI significantly increased the risk of upgrading, upstaging, seminal vesicle invasion, and any outcome by 21%, 23%, 27%, and 20%, respectively. The differences between areas under the receiver operating characteristics curves comparing models with and without BMI were statistically significant for upgrading (P = 0.0002), upstaging (P = 0.0007), and any outcome (P = 0.0001).ConclusionsBMI should be a selection criterion for inclusion of patients with low-risk PCa in AS programs. Our results support the idea that obesity is associated with worse prognosis and suggest that a close AS program is an appropriate treatment option for obese subjects.     

The effect of combined androgen blockade on bone turnover and bone mineral density in men with prostate cancer

Summary Our study and previous reports suggest that castration results in increased bone turnover and lowered BMD and that these changes might be attenuated by anti-androgens, such as BL and EMP. Introduction Recent studies have shown that castration for PC decreases bone mineral density (BMD), while estrogen therapy or bicalutamide (BL) monotherapy maintains BMD. However, the effect of combined androgen blockade (CAB) on bone turnover is not well studied. Methods A total of 204 men were evaluated in the study (control group: n = 56, castration group: n = 102, ‘CAB with BL’ group: n = 22, ‘CAB with estramustine phosphate (EMP)’ group: n = 24). We measured steroid hormone levels, BMD (measured at one-third distal radius), bone turnover markers (levels of urinary N-telopeptide cross links of type 1 collagen (u-NTx) and deoxypyridinoline (u-DPD), serum concentrations of osteocalcin (OC)) in order to assess differences between groups. Results The BMD % Z score of the castration group was significantly lower than that of the control group or the ‘CAB with EMP’ group (90.6% vs. 95.5%, 98.6%; p < 0.042, p < 0.044, respectively). Levels of u-NTx, u-DPD, OC of the castration group were the highest followed by the control group, then the ‘CAB with BL’ group and the ‘CAB with EMP’ group. Conclusions Our study and previous reports suggests that castration results in increased bone turnover and lowered BMD and that these changes might be attenuated by anti-androgens, such as BL and EMP.     

血清网膜素-1与前列腺癌的相关性研究

目的：研究血清脂肪因子网膜素-1(omentin-1)与前列腺癌的相关性.方法2015年7月至2016年3月我科收治的前列腺癌患者44例作为肿瘤组,同期前列腺增生患者42例作为对照组,两组患者的年龄相匹配,均空腹经肘静脉采集血液,ELISA 法测定血清 omentin-1水平.结果与对照组相比,肿瘤组患者 omentin-1、PSA、高密度脂蛋白胆固醇(HDL-C)水平明显升高,差异有统计学意义(P ＜0．05).各项参数的 Spearman 相关性分析显示 omentin-1与 HDL-C、PSA水平呈正相关(分别 r ＝0．363,P ＝0．0006;r ＝0．356,P ＝0．0008),与空腹血糖水平呈负相关(r ＝－0．230,P ＝0．033).二项 Logistic 回归分析显示 omentin-1水平的独立影响因素是肿瘤分组,即罹患前列腺癌是使患者血清 omentin-1水平升高的一个独立影响因素(P ＝0．0004).结论血清脂肪因子 omentin-1水平在前列腺癌与前列腺增生患者间有显著差异,提示其可能与前列腺癌的发生发展相关.     

Molecular correlates of intermediate- and high-risk localized prostate cancer

Clinicopathologic parameters, including Gleason score, remain the most validated prognostic factors for patients diagnosed with localized prostate cancer (PCa). However, patients of the same risk groups have exhibited heterogeneity of disease outcomes. To improve risk classification, multiple molecular risk classifiers have been developed, which were designed to inform beyond existing clinicopathologic classifiers. Alterations affecting tumor suppressors and oncogenes, such as PTEN, MYC, BRCA2, and TP53, which have been long associated with aggressive PCa, demonstrated grade-dependent frequency of alterations in localized PCas. In addition to these genetic hallmarks, several RNA-based commercial tests have been recently developed to help identify men who would benefit from earlier interventions. Large genomic studies also correlate germline genetic alterations and epigenetic features with adverse outcomes, further strengthening the link between the risk of metastasis and a stepwise accumulation of driver molecular lesions.     

Overexpression of nuclear AR-V7 protein in primary prostate cancer is an independent negative prognostic marker in men with high-risk disease receiving adjuvant therapy

Background

Overexpression of the androgen receptor (AR) splice variant 7 (AR-V7) has recently been reported to be associated with resistance to antihormonal therapy. Herein, we address the question whether tumor cells with AR-V7 expression can be detected at the time of radical prostatectomy, that is, before long-term hormonal manipulation and castration resistance, and what the potential prognostic impact on the biochemical recurrence (BCR)-free survival may be.

Prevalent and incident use of androgen deprivation therapy among men with prostate cancer in the United States

Purpose

Androgen deprivation therapy (ADT) for prostate cancer increased substantially through the 1990s, but more recent national trends regarding incident and prevalent use have been incompletely characterized.

Methods

Linked Surveillance, Epidemiology, and End Results (SEER)–Medicare data were used to study patterns of ADT utilization. Prevalence of ADT in the male Medicare population was estimated by examining a cohort of prostate cancer patients and a 5% noncancer control population, from 1991 to 2005. ADT use across different indications was examined for men with incident cancers from 2000 to 2002. Nested logit models were used to examine determinants of ADT use in men with lower risk prostate cancer not treated definitively by surgery or radiation.

Results

Prevalent ADT use increased through the 1990s, peaked in 2000 at 3.17% of all male Medicare beneficiaries, subsequently stabilized, then dropped in 2005 to 2.92%. Between 2000 and 2002, use in incident prostate cancer was stable, with 44.8% use in all cases, 15% of cases as an adjuvant with radiation, and 14% as a primary therapy. In the nested logit model, predictors of ADT use in a lower risk setting were older age, higher stage and grade, and elevated prostate-specific antigen levels.

Conclusions

Following a period of rapid expansion during the 1990s, incident and prevalent use of ADT has leveled, and may be starting to decline. Further research is needed to monitor how reductions in reimbursement for GnRH agonists will affect appropriate use of ADT as well as use in settings where its benefits may be marginal.     

Radical prostatectomy in high-risk and locally advanced prostate cancer: Mayo Clinic perspective

PurposeMen diagnosed with high-risk prostate cancer represent the cohort of prostate cancer patients at greatest risk for subsequent disease-specific mortality. Unfortunately, however, the classification of high-risk tumors remains imprecise and heterogeneous. There has been a historical reluctance to offer such patients aggressive local treatment, and considerable debate exists regarding the optimal management in this setting.MethodsWe present here our institutional experience, as well as data from several other centers, with radical prostatectomy for high-risk tumors.ResultsWe discuss that surgery affords accurate pathological staging, thereby improving the identification of patients for secondary therapies. Moreover, prostatectomy not only provides durable local disease control but in addition numerous contemporary surgical series in high-risk patients have shown radical prostatectomy to be associated with excellent long-term cancer-specific survival. Further, although studies comparing surgical and radiotherapy modalities in high-risk prostate patients have been wrought with methodological challenges, consistently these observational studies have found equivalent to improved oncologic outcomes when surgery is utilized as the primary treatment.ConclusionsHerein, we review the advantages, long-term outcomes, and technique of surgery for high-risk prostate cancer.