根治性外放射治疗与根治性前列腺切除术治疗局限性高危前列腺癌的疗效比较

目的 比较根治性外放射治疗（ExRT）与根治性前列腺切除术（RP）治疗局限性高危前列腺癌患者的疗效。方法 回顾性分析诊断为高危前列腺癌（T2b-T4N0M0）并接受ExRT或RP的150例患者。高危前列腺癌的入选标准为PSA≥20 ng/ml或cT3以上或GS≥8。主要研究终点为无生化复发生存期,次要研究终点为无远处转移生存期、癌症特异性生存期及总生存期。结果 88例患者接受了ExRT及雄激素剥夺治疗（ADT）,其余62例患者接受了RP及盆腔淋巴结清扫术（PLND）。两组患者的中位年龄（68.9±5.2 vs. 64.3±6.5岁, P=0.012）及中位随访时间（60.2±32.3 vs. 45.8±25.5月,P=0.005）差异有统计学意义。ExRT组患者生化复发率显著低于RP组患者（23.9% vs. 58.1%, P<0.001）,而无生化复发患者生存期显著延长（96.2±7.4 vs. 38.7±4.6月, P<0.001）。两组无远处转移生存期、癌症特异性生存期及总生存期差异均无统计学意义。结论 与RP相比,接受ExRT治疗的局限性高危前列腺癌患者生化复发率低,无生化复发生存期显著延长。     

Prostate Cancer Incidence and Mortality in Relationship to Family History of Prostate Cancer; Findings From The PLCO Trial

BackgroundThe purpose of the study was to determine the relationship between family history of prostate cancer in a first-degree relative (FDR) and prostate cancer incidence and mortality.Patients and MethodsDeidentified data sets of men recruited in the Prostate, Lung, Colorectal, and Ovary (PLCO) trial were accessed. Men with complete information about family history of prostate cancer in an FDR were included. The effect of family history on prostate cancer incidence and mortality was assessed in a multivariate Cox regression model. Likewise, the effect of the number of FDRs with prostate cancer and the effect of youngest diagnosis age of an FDR with prostate cancer were assessed.ResultsA total of 74,781 participants were included in the current analysis, including 5281 participants with family history of prostate cancer in an FDR and 69,500 participants without family history of prostate cancer in an FDR. Among participants without family history of prostate cancer in an FDR, a total of 7450 patients (10.5%) were subsequently diagnosed with prostate cancer; whereas among patients with family history of prostate cancer in an FDR, a total of 889 patients (16.5%) were subsequently diagnosed with prostate cancer. In an adjusted multivariate Cox regression model, family history of prostate cancer was associated with a higher probability of prostate cancer diagnosis (hazard ratio [HR], 1.590; 95% confidence interval [CI], 1.482-1.705; P < .001). The number of FDRs with prostate cancer proportionally correlated with higher prostate cancer incidence (HR, 1.529; 95% confidence interval [CI], 1.439-1.624; P < .001). Family history of prostate cancer in an FDR was not predictive of higher prostate cancer mortality in the PLCO screening (intervention) arm (HR, 0.829; 95% CI, 0.422-1.629; P = .587) whereas it was predictive of a higher prostate cancer mortality in the PLCO nonscreening (control) arm (HR, 1.894; 95% CI, 1.154-3.109; P = .012). Number of FDRs with prostate cancer was not associated with higher prostate cancer mortality in the PLCO screening (intervention) arm (HR, 0.956; 95% CI, 0.541-1.691; P = .878), whereas it was associated with higher prostate cancer mortality in the PLCO nonscreening (control) arm (HR, 1.643; 95% CI, 1.083-2.493; P = .020).ConclusionFamily history of prostate cancer is associated with an increased risk of prostate cancer diagnosis in the overall cohort of patients as well as a higher risk of prostate cancer mortality in the nonscreened subcohort. Further prospective assessment of the role of screening among selected high-risk populations (including those with strong family history) is warranted.     

Survival Outcomes for Metastatic Prostate Cancer Patients Treated With Radical Prostatectomy or Radiation Therapy: A SEER-based Study

BackgroundPatients with metastatic prostate cancer (mPCa) have a very low 5-year survival rate. How to choose proper treatment of mPCa remains controversial.MethodWithin the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015), we performed analyses of cancer-specific mortality (CSM) and overall mortality (OM) in the comparisons of local treatment (LT) versus no local treatment (NLT) and radical prostatectomy (RP) versus radiation therapy (RT). To balance the characteristics between 2 treatment groups, propensity score matching was performed. Considering the selection bias, we additionally used an instrument variate (IVA) to calculate the unmeasured confounders.ResultMultivariate regression showed that patients receiving LT had the lower risks of OM and CSM after adjustment of covariates (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.35-0.44 and HR 0.39, 95% CI 0.34-0.45). In the IVA-adjusted model, LT showed more survival benefits compared with NLT, with HR of 0.57 (95% CI 0.50-0.65) and cancer-specific HR of 0.59 (95% CI 0.51-0.68), respectively. For those receiving LT, adjusted multivariate regression indicated that RP is superior to RT (HR 0.60; 95% CI 0.43-0.83 for OM and HR 0.61; 95% CI 0.42-0.91 for CSM). The IVA-adjusted model also showed that RP presented with potentially better survival outcome compared with RT, although the effect was not statistically significant (HR 0.63; 95% CI 0.26-1.54 for OM and HR 0.47; 95% CI 0.16-1.35 for CSM).ConclusionAmong patients with metastatic prostate cancer, LT might bring better survival benefits in decreasing CSM and all-cause mortality compared with NLT. For those receiving LT, RP showed better survival outcomes than RT.     

MRI-Detectability of Clinically Significant Prostate Cancer Relates to Oncologic Outcomes After Prostatectomy

Introduction/BackgroundMagnetic resonance imaging (MRI) misses a proportion of “clinically significant” prostate cancers (csPC) as defined by histopathology criteria. The aim of this study was to analyze whether long-term oncologic outcomes differ between MRI-detectable and MRI-occult csPC.Patients and MethodsRetrospective analysis of 1449 patients with pre-prostatectomy MRI and csPC on prostatectomy specimens (ie, Grade group ≥2 or extraprostatic spread) between 2001-2006. T2-weighted MRIs were classified according to the Prostate Imaging Reporting and Data System into MRI-occult (categories 1, 2), MRI-equivocal (category 3), and MRI-detectable (categories 4, 5). Cumulative incidence of biochemical recurrence (BCR), metastatic disease, and cancer-specific mortality, estimated with competing risk models. The median follow-up in survivors was 11.0 years (IQR: 8.9-13.1).ResultsIn 188 (13%) cases, csPC was MRI-occult, 435 (30%) MRIs were equivocal, and 826 (57%) csPC were MRI-detectable. The 15-year cumulative incidence [95% CI] of BCR was 8.3% [2.2, 19.5] for MRI-occult cases, 17.4% [11.1, 24.8] for MRI-equivocal cases, and 43.3% [38.7, 47.8] for MRI-detectable cases (P < .001). The cumulative incidences of metastases were 0.61% [0.06, 3.1], 3.5% [1.5, 6.9], and 19.6% [15.4, 24.2] for MRI-occult, MRI-equivocal, and MRI-detectable cases, respectively (P < .001). There were no deaths from prostate cancer observed in patients with MRI-occult csPC, compared to an estimated 1.9% [0.54, 4.9], and 7.1 % [4.5, 10.6] for patients with MRI-equivocal and MRI-detectable cancer, respectively (P < .001).ConclusionOncologic outcomes after prostatectomy for csPC differ between MRI-occult and MRI-detectable lesions. Judging the clinical significance of a negative prostate MRI based on histopathologic surrogates alone might be misleading.MicroabstractAmong 1449 patients with pre-prostatectomy MRI and clinically significant prostate cancer on prostatectomy histopathology, MRI-occult cancers (n = 188, 13%) were less likely to recur biochemically (8% vs. 43%, P < .001), metastasize (0.6% vs. 20%, P < .001), or lead to prostate cancer mortality (0% vs. 7%, P < .001) than MRI-detectable cancers (n = 826, 57%). MRI-occult cancers constitute a prognostically distinct subgroup among higher-grade prostate cancers.     

Active Surveillance Versus Radical Prostatectomy in Favorable-risk Localized Prostate Cancer

BackgroundActive surveillance (AS) and radical prostatectomy (RP) are both accepted treatments for men with favorable-risk localized prostate cancer (PCa) (ie, clinical tumor category 1-2b, Gleason Grade Group 1-2, and prostate-specific antigen < 20 ng/mL). However, head-to-head studies comparing oncologic outcomes and survival between these 2 treatment strategies are warranted. The objective of this study was to compare the use of prostate cancer treatments and PCa death in men managed on AS and men who underwent immediate RP.Patients and MethodsThis was an observational study including 647 men on AS and 647 men treated with RP propensity score matched. We examined the 10-year cumulative incidence of salvage radiotherapy, hormonal therapy, castration-resistant PCa, and PCa death.ResultsThe 10-year curative treatment-free survival for men on AS was 61% (95% confidence interval [CI], 57%-65%). No differences in use of salvage radiotherapy (AS, 2.7%; 95% CI, 1.4%-4.1% vs. RP 5.4%; 95% CI, 3.4%-7.3%), hormonal therapy (AS, 6.9%; 95% CI, 4.4%-9.4% vs. RP, 4.1%; 95% CI, 2.5%-5.6%), developing castration-resistant PCa (AS, 1.7%; 95% CI, 0.5%-2.9% vs. RP, 2.0%; 95% CI, 0.7%-3.4%), or cumulative PCa mortality (AS, 0.4%; 95% CI, 0%-1.0% vs. RP, 0.5%; 95% CI, 0%-1.5%) were observed between the treatment strategies. The main limitation was the non-random allocation to treatment strategy.ConclusionIn this observational study on men with favorable-risk localized PCa, we found similar PCa mortality at 10 years between men on AS and men who underwent immediate RP. Moreover, there were no differences in the use of PCa therapies between the groups. Our study supports active surveillance as a treatment strategy for men with favorable-risk localized PCa.     

术后放疗对前列腺癌根治术患者预后影响的荟萃分析

[目的]对前列腺癌根治术后患者术后放疗的有效性和安全性进行系统评价。[方法]计算机检索PubMed、EMBASE、Cochrane Library、CBM、CNKI、VIP2010年6月份之前发表的有关术后放疗治疗前列腺癌的随机对照试验,有2位研究员独立对纳入文献进行质量评价和数据提取,用RevMan5.0软件统计分析。[结果]共纳入4篇随机对照试验共计1778例患者,Meta分析结果显示:前列腺癌根治术联合术后放疗与单纯的前列腺癌根治术治疗前列腺癌在总生存时间(HR=0.88,95%CI:0.67～1.14)方面差异无统计学意义,但在生化无进展生存时间(HR=0.47,95%CI:0.40～0.56)方面差异有统计学意义。[结论]当前证据表明术后放疗可以提高前列腺癌根治术患者的生化无进展生存时间,但是并不能提高患者的总生存时间。     

安卡合并放射治疗鼻咽癌5年随访观察

目的:马蔺子素(安卡胶囊)是从中草药马蔺子(Irisquinones)的种皮中所提取出来的一种醌类化合物,为观察安卡合并放射治疗鼻咽癌的增敏疗效进行本次观察.方法:1995年3月～1996年3月在广州中山医科大学附属肿瘤医院,将病理证实为鼻咽癌Ⅰ～Ⅳa期(92福州分期)的患者104例,随机分为单纯放疗组(简称单放组)52例和马蔺子素与放射联合治疗组(简称药放组)52例进行临床观察.采用Co60治疗机、能量为1.25MeV的γ射线连续照射,常规放疗.结果:5年生存随访结果提示:单放组5年生存率66%,药放组5年生存率67%,药放组生存率高于单放组,但是无统计学差异(P＞0.05);同时还比较了两组患者在张口困难、听力下降、脑脊髓病等远期反应的发生率,无统计学差别.通过生存统计(Cox)模型,筛选出影响生存的主要因素是患者分期的早晚和是否出现放疗失败.结论:安卡配合放射治疗鼻咽癌能否提高远期疗效,仍需追踪观察和扩大病例、以及增加病种试验.     

Phase II Trial of Neoadjuvant Docetaxel and CG1940/CG8711 Followed by Radical Prostatectomy in Patients With High‐Risk Clinically Localized Prostate Cancer

Background.

Prostate cancer (PC) is the most commonly diagnosed noncutaneous malignancy in American men. PC, which exhibits a slow growth rate and multiple potential target epitopes, is an ideal candidate for immunotherapy. GVAX for prostate cancer is a cellular immunotherapy, composed of PC-3 cells (CG1940) and LNCaP cells (CG8711). Each of the components is a prostate adenocarcinoma cell line that has been genetically modified to secrete granulocyte-macrophage colony-stimulating factor. Hypothesizing that GVAX for prostate cancer could be effective in a neoadjuvant setting in patients with locally advanced disease, we initiated a phase II trial of neoadjuvant docetaxel and GVAX. For the trial, the clinical effects of GVAX were assessed in patients undergoing radical prostatectomy (RP).

Methods.

Patients received docetaxel administered at a dose of 75 mg/m² every 3 weeks for 4 cycles. GVAX was administered 2–3 days after chemotherapy preoperatively for four courses of immunotherapy. The first dose of GVAX was a prime immunotherapy of 5×10⁸ cells. The subsequent boost immunotherapies consisted of 3×10⁸ cells. After RP, patients received an additional six courses of immunotherapy. Pathologic complete response, toxicity, and clinical response were assessed. The primary endpoint of the trial was a pathologic state of pT0, which is defined as no evidence of cancer in the prostate.

Results.

Six patients completed neoadjuvant docetaxel and GVAX therapy. No serious drug-related adverse events were observed. Median change in prostate-specific antigen (PSA) following neoadjuvant therapy was 1.47 ng/ml. One patient did not undergo RP due to the discovery of positive lymph nodes during exploration. Of the five patients completing RP, four had a downstaging of their Gleason score. Undetectable PSA was achieved in three patients at 2 months after RP and in two patients at 3 years after RP.

Conclusions.

Neoadjuvant docetaxel/GVAX is safe and well tolerated in patients with high-risk locally advanced PC. No evidence of increased intraoperative hemorrhage or increased length of hospital stay postoperatively was noted. These results justify further study of neoadjuvant immunotherapy.     

Safety and Feasibility of Radiation Therapy to the Primary Tumor in Patients With Metastatic Castration-resistant Prostate Cancer

IntroductionThe objective of this study was to evaluate the safety and feasibility of radiation therapy (RT) to the primary tumor in patients with metastatic castration-resistant prostate cancer (mCRPC).Patients and MethodsThis retrospective study included 105 patients with mCRPC who were treated between April 2004 and May 2019. We divided the patients into 2 groups: patients treated with RT to the primary tumor after they developed CRPC (RT group) and without (non-RT group). The primary purpose was safety assessed using the Common Terminology Criteria for Adverse Events. The secondary purpose included prostate-specific antigen (PSA) response, cancer-specific survival (CSS), and overall survival (OS). Background-adjusted multivariate analyses, with the inverse probability of treatment weighting (IPTW) method, were performed to evaluate impact of RT on CSS and OS.ResultsThe median age at CRPC diagnosis was 75 years, and the median follow-up period after CRPC diagnosis was 21 months. The adverse events rates related to RT in any grade and grade ≥ 3 were 55% and 23%, respectively. Nine (29%) patients achieved ≥ 30% PSA decline with RT. In multivariate analyses with the IPTW method, the CSS and OS in the RT group were significantly longer than those in the non-RT group. In subgroup analyses with the IPTW method, RT was significantly associated with improved OS in patients aged ≥ 75 years and patients with initial PSA ≥ 500 ng/mL, cT4, Gleason score ≥ 8, and high-volume metastatic burden.ConclusionsRT to the primary tumor is safe and feasible, and it has potential benefits on oncologic outcomes in patients with mCRPC.     

Rates of Positive Surgical Margins and Their Effect on Cancer-specific Mortality at Radical Prostatectomy for Patients With Clinically Localized Prostate Cancer

Background

The objective of this study was to investigate positive surgical margin (PSM) rates in patients with prostate cancer treated with radical prostatectomy (RP) and assess PSM impact on cancer-specific mortality (CSM).

替莫唑胺联合放疗治疗胶质瘤患者的生存情况分析

目的 探讨分析替莫唑胺联合放疗治疗对胶质瘤患者生存情况的影响.方法 选取64例胶质瘤患者为研究对象,采用数字表法将其平均分成两组,对照组患者在术后行放疗,观察组患者在放疗基础上联合应替莫唑胺化疗,比较两组患者治疗后的生存情况及不良反应情况.结果 观察组临床疾病控制率(50.00％)明显高于对照组(25.00％),有统计学意义(P＜0.05);观察组患者无进展生存时间为(11.24±3.09)个月和生存时间为(15.64±3.87)个月,较对照组患者的无进展生存时间[(6.09±1.97)个月]和生存时间[(8.71±2.56)个月]明显要长,有统计学意义(P＜0.05);观察组患者白细胞下降、头皮溃疡、恶心呕吐、腹泻、血小板计数下降等不良反应发生率均低于对照组,均可自行缓解或对症用药后可控制.结论 胶质瘤患者术后采用替莫唑胺联合放疗治疗,与单纯的放疗相比较,能够有效控制肿瘤生长情况,延长患者无进展生存时间和总生存时间,治疗期间不良反应少,安全有效.     

Clinical Outcomes from Dose-Reduced Radiotherapy to the Prostate in Elderly Patients with Localized Prostate Cancer

Radical treatment of localized prostate cancer in elderly patients may lead to unacceptable treatment-associated toxicities that adversely impact quality of life without improving survival outcomes. This study reports on a cohort of 54 elderly (>70 years) patients that received 4000–5000 cGy of palliative external beam radiotherapy (EBRT) as an alternative to androgen deprivation therapy (ADT). The primary outcome of interest was the period of ADT-free survival, and secondary outcomes included overall survival (OS) and metastases-free survival (MFS). Kaplan–Meier regression was used to estimate survival outcomes. Thirty-six (67%) patients achieved a break in ADT post-radiotherapy, with a median time to ADT reinitiation of 20 months. Common Terminology Criteria for Adverse Events (CTCAE) were limited to low-grade gastrointestinal (GI) or genitourinary (GU) toxicities, with no skin toxicities observed. Grade 1 GI toxicity was observed in 9 (17%) patients, and grades 1 and 2 GU toxicities were observed in 13 (24%) and 3 (6%) patients, respectively, with no higher-grade toxicities reported. Five-year MFS and OS were 56% and 78%, respectively. In summary, the treatment regimen was well-tolerated and achieved durable ADT-free survival in most patients. Dose-reduced EBRT appears to be a viable alternative to ADT in elderly patients with localized prostate cancer.