Randomized trial comparing cryoablation and external beam radiotherapy for T2C-T3B prostate cancer

The objective was to evaluate the relative efficacy of cryoablation (CRYO) versus external beam radiation (EBRT) for clinically locally advanced prostate cancer in a randomized clinical trial. Patients with histologically proven, clinically staged as T2C, T3A or T3B disease were randomized with 6 months of perioperative hormone therapy to one of the two procedures. Owing largely to a shift in practice to longer term adjuvant hormonal therapy and higher doses of radiation for T3 disease, only 64 out of the planned 150 patients were accrued. Twenty-one of 33 (64%) in the CRYO group and 14 of 31 (45%) in the EBRT-treated group who had met the ASTRO definition of failure were also classified as treatment failure. The mean biochemical disease-free survival (bDFS) was 41 months for the EBRT group compared to 28 months for the CRYO group. The 4-year bDFS for EBRT and CRYO groups were 47 and 13%, respectively. Disease-specific survival (DSS) and overall survival (OS) for both groups were very similar. Serious complications were uncommon in either group. EBRT patients exhibited gastrointestinal (GI) adverse effects more frequently. Taking into account the relative deficiency in numbers and the original trial design, this prospective randomized trial indicated that the results of CRYO were less favorable compared to those of EBRT, and was suboptimal primary therapy in locally advanced prostate cancer.     

Interstitial gold and external beam irradiation for prostate cancer

We treated 65 patients with prostatic cancer confined clinically to the prostate or periprostatic area during an 8-year period. Seven patients had stage A2, 38 stage B and 20 stage C disease. All 65 patients underwent staging pelvic lymphadenectomy and implantation of gold grains into the prostate (mean dose 3,167 rad). A total of 64 patients then completed a course of external beam irradiation to a mean total tumor dose of 6,965 rad. Complications of therapy were mild and limited (less than 3 months in duration) in most patients, and they included radiation cystitis (32 per cent), diarrhea (31 per cent), extremity lymphedema (7.7 per cent) and wound infection (3 per cent). Two patients suffered urinary incontinence after therapy and 2 (3 per cent) had diarrhea more than 3 months in duration. The actuarial 5-year survival rate for all patients was 87 per cent and the 5-year survival free of disease was 72 per cent.     

Prostate specific antigen bounce after radioactive seed implantation followed by external beam radiation for prostate cancer

PURPOSE: Prostate specific antigen (PSA) may temporarily increase following radiotherapy for prostate cancer without signaling cancer recurrence. We describe this phenomenon which is called PSA bounce. MATERIALS AND METHODS: From 1984 to 1995, 779 stage T1T2N0 cancer cases were treated with simultaneous radiotherapy with a 125iodine prostate implant followed by external beam radiation. Median pretreatment PSA was 7.7 ng./ml. (range 0.3 to 188). PSA bounce was defined as an increase of 0.1 ng./ml. or greater above the preceding PSA level after simultaneous radiation followed by a subsequent decrease below that level. Disease-free status was defined as the ability to achieve and maintain posttreatment PSA 0.2 ng./ml. or less. RESULTS: PSA bounce was observed in 35% of men (273 of 779). Median time to PSA bounce was 18 months from the time of implant and 92% of bounces were observed within 36 months. Median pre-bounce PSA was 0.7 ng/ml. (range 0.1 to 8.9) and median bounce height (increase above the pre-bounce level) was 0.4 ng./ml. (range 0.1 to 15.8). No distinguishing characteristics were observed between men with PSA bounce and those with cancer recurrence, and bounce had no prognostic significance relative to recurrence. CONCLUSIONS: PSA bounce is common following seed implantation for prostate cancer. It produces anxiety in men previously treated for prostate cancer and confounds the diagnosis of recurrence.     

Salvage permanent perineal radioactive‐seed implantation for treating recurrence of localized prostate adenocarcinoma after external beam radiotherapy

OBJECTIVE

To assess our experience with salvage permanent perineal radioactive‐seed implantation (SPPI) as a possible therapeutic option for recurrent prostate adenocarcinoma, as salvage therapies for recurrences after definitive external beam radiotherapy (EBRT) for localized adenocarcinoma of the prostate are associated with significant morbidity and biochemical failure.

PATIENTS AND METHODS

We retrospectively analysed on patients who had SPPI for localized recurrent prostate adenocarcinoma from 1996 to 2007 after primary treatment with EBRT. Excluded were patients who had other primary treatment or had no follow‐up. Primary outcomes were time to biochemical relapse‐free survival, using the Phoenix definition of a prostate‐specific antigen (PSA) nadir +2 ng/mL, and cancer‐specific survival. Secondary outcomes were the International Prostate Symptom Score (IPSS), the International Index of Erectile Function‐5 score (IIEF‐5), and complications based on Common Terminology Criteria for Adverse Events (version 3).

RESULTS

In all, 37 patients had SPPI during this period; after applying inclusion and exclusion criteria, 24 remained for analysis. At the time of salvage therapy, the median time to the diagnosis of local recurrence was 49 months, the median PSA level was 3.36 ng/mL, the median PSA doubling time was 20 months, and all patients were clinically re‐staged at ≤T2 with negative transrectal ultrasonography and/or magnetic resonance spectroscopy. The original Gleason score was ≤6 in nine patients, 7 in eight and ≥8 in three (not recorded in two). The median follow‐up after SPPI was 30 months; the cancer‐free survival was 96% (one death) and biochemical relapse‐free survival was 88% (three patients). The PSA level was higher than the levels before SPPI at 3 months in all three failures, but lower in all 21 patients considered relapse‐free. Complications included one urethral stricture, one grade 3 rectal haemorrhage and five grade 2 gross haematuria that resolved with conservative management. Insufficient data were available to assess the IPSS or IIEF‐5 scores.

CONCLUSION

With a short‐term follow‐up SPPI appears to provide excellent prostate cancer control with an acceptable rate of complications for patients with local recurrence of prostate cancer after EBRT. An extended follow‐up is necessary to determine the long‐term durability and safety of SPPI.     

Radiotherapy for stage B prostate cancer]

Thirty five cases with stage B prostate cancer underwent radiotherapy to the primary lesion from 1965 to 1989 in our hospital. Twenty two of them were given radiotherapy alone and 13 were treated by radiotherapy combined with hormone therapy. Twenty nine of them were given 113 or 127 TDF (Time, Dose and Fraction) of external radiotherapy using linear accelerator. Three of the other 6 cases underwent external radiotherapy combined with administration of bleomycin and the others received intraoperative irradiation by electron beam. We defined on digital examination a reduction in the primary lesion as improvement and complete flattening as atrophy for evaluation of the treatment. Rates of the improvement were 95% in radiation, alone, and 100% in hormone and radiation combination. Atrophy rates were 62% in the former, and 92% in the latter. Five-year non-relapse rates were 85% and 100%, respectively. Four cases relapsed in the radiotherapy alone group, in which two cases given intraoperative irradiation relapsed in the primary lesion and another two given external radiotherapy in the pelvic nodes and required further treatment. One of the 2 relapsed cases with intraoperative irradiation has been alive with cancer and the other died from dissemination. One of the 2 relapsed cases with external radiotherapy has been alive and well and the other died at home without any information of death. One relapsed in the combination group at 130 months but has been alive despite gradually progressive dissemination for 185 months. All relapsed cases were those with atrophy group. No relapse was seen in cases without atrophy of the prostate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Combined external radiotherapy and hormonal therapy for localized carcinoma of the prostate

Forty-nine patients with localized carcinoma of the prostate were treated by external radiotherapy together with hormonal manipulation and were followed up to six years. Hormonal manipulation included bilateral orchiectomy and diethylstilbestrol, 3 mg/day. The cumulative five-year survival for the 49 patients was 87.6%, with 11 % progression rate to stage D during that period. In 40 patients (81.6%), a decrease in the size of the prostate was noted. In none of the patients was there local recurrence of the tumor during the period of follow-up. Transient gastrointestinal and/or urinary symptoms occurred following radiotherapy in 11 patients (22.4%), and in four patients severe cystitis or proctitis appeared. Complications related to hormonal therapy occurred in 11 patients (22.4%). The high survival rates reported herein, together with the low progression rate to stage D during six years of follow-up, may justify the early institution of radiotherapy in combination with hormonal manipulation for patients with localized carcinoma of the prostate. A randomized study with an extended number of patients is underway to further evaluate this mode of therapy.     

The frequency and morbidity of local tumor recurrence after definitive radiotherapy for stage C prostate cancer

Radiotherapy is reported to provide good control of locally advanced prostate cancer. However, few long-term studies have assessed the morbidity related to local tumor recurrence in patients treated with radiotherapy alone (without hormonal manipulation). To determine the frequency and severity of morbidity related to local recurrence we reviewed the course of all patients with clinical stage C prostate cancer treated at our institution between 1966 and 1979 with bilateral pelvic lymph node dissection, radioactive gold seed implantation and external beam irradiation therapy to the prostate. Of the 121 patients 60% died and the 40% still alive at the time of review were followed for a mean of 8.1 years (range 3.3 to 14.8 years). Over-all, 64 patients (53%) had local recurrence, which was defined as a clinical event causing signs or symptoms and was proved by biopsy. On an actuarial basis the risk of local recurrence was 43 +/- 10% (mean +/- 2 standard errors) at 5 years and 74 +/- 11% at 10 years. Any symptomatic episode requiring active intervention or causing morbidity was denoted an adverse event. There were 162 adverse events among the 73 patients (2.2 adverse events per patient): 69% of these were severe (requiring surgical intervention) and 55% were chronic (more than 3 months in duration). The most common cause of an adverse event was bladder outlet obstruction requiring transurethral resection of the prostate (44 patients); 16 patients (13%) became incontinent. Hydronephrosis developed in 24 patients (20%). Local recurrence after definitive radiotherapy for our patients with stage C prostate cancer was common and was associated with serious morbidity, frequently requiring surgical intervention. Radiotherapy alone may not be sufficient to provide long-term local control of stage C prostate cancer.     

Clinical study of endocrine therapy in stage B and C prostate cancer

To evaluate the usefulness of endocrine therapy for stage B and C prostate cancer, we carried out a retrospective study on overall survival rate, cause-specific survival, PSA recurrence-free rate, and their predictive factors in 118 patients with stage B prostate cancer, 61 with stage C prostate cancer who underwent endocrine therapy at our department between 1985 and 2001. The cause-specific survival rate and PSA recurrence-free rate of stage B patients who underwent endocrine therapy were well, and they will take a good clinical course. Thus, in this stage of prostate cancer, aged patients and patients with complications may be good candidates for endocrine therapy. The cause-specific survival rate and PSA recurrence-free rate in the stage C patients who underwent endocrine therapy were significantly low. In stage C patients, endocrine therapy should be combined early with other methods such as radiotherapy. In the stage B patients who underwent endocrine therapy, PSA and Gleason score appeared to be associated with the cause-specific survival rate and PSA recurrence-free rate.     

经尿道前列腺电切术治疗前列腺癌粒子植入术后尿潴留(2例报告附文献复习)

目的:观察经尿道前列腺电切术治疗前列腺癌粒子植入术后尿潴留的疗效。方法:2005年到2008年,2例前列腺癌粒子植入术后排尿困难、尿潴留患者,行经尿道前列腺电切术。结果:2例患者手术均获得成功,手术时间平均60 min,原夜尿次数5～6次/夜、现夜尿次数2次/夜,术后患者IPSS症状评分及生活质量评分明显提高。结论:前列腺癌粒子植入术后尿潴留患者应用经尿道前列腺电切仍能够取得明显疗效。     

Salvage brachytherapy for locally recurrent prostate cancer after external beam radiotherapy

External beam radiotherapy (EBRT) is a standard treatment for prostate cancer. Despite the development of novel radiotherapy techniques such as intensity-modulated conformal radiotherapy, the risk of local recurrence after EBRT has not been obviated. Various local treatment options (including salvage prostatectomy, brachytherapy, cryotherapy, and high-intensity focused ultrasound [HIFU]) have been employed in cases of local recurrence after primary EBRT. Brachytherapy is the first-line treatment for low-risk and selected intermediate-risk prostate tumors. However, few studies have examined the use of brachytherapy to treat post-EBRT recurrent prostate cancer. The purpose of this paper is to analyze the current state of our knowledge about the effects of salvage brachytherapy in patients who develop locally recurrent prostate cancer after primary EBRT. This article also introduces our novel permanent brachytherapy salvage method.There are various treatment options for patients who develop locally recurrent prostate cancer after primary EBRT. Agarwal et al. reported that androgen-deprivation therapy (ADT) was the most common salvage treatment (93.5%) for post-EBRT recurrent prostate cancer and that salvage brachytherapy was only performed in 0.2% of cases.1 The benefits of ADT are well-known; however, it is also associated with various adverse effects including a loss of libido, impotence, anemia, an increased incidence of skeletal fractures, and a higher cardiovascular mortality rate. Various local salvage treatment options including brachytherapy, radical prostatectomy, cryotherapy, and HIFU have been used to treat post-EBRT locally recurrent prostate cancer. Whole-gland salvage brachytherapy has demonstrated acceptable oncological outcomes; however, it can have significant side effects including incontinence, genitourinary toxicities, and gastrointestinal toxicities.2,3 Recently, focal salvage brachytherapy has been used to treat post-EBRT locally recurrent prostate cancer in order to reduce the frequency of adverse events while maintaining appropriate cancer control rates.4,5 However, only a few reports about focal salvage brachytherapy for post-EBRT locally recurrent prostate cancer have been published. In this article, we analyze the use of whole-gland and focal brachytherapy for post-EBRT locally recurrent prostate cancer, focusing on their clinical outcomes and toxicity. Recently, we started performing focal salvage brachytherapy based on three-dimensional cancer mapping data obtained using magnetic resonance imaging (MRI)-transrectal ultrasound (TRUS) fusion biopsy examinations. Herein, we introduce our novel permanent brachytherapy salvage method.     

Sexual health recovery after prostatectomy,external radiation,or brachytherapy for early stage prostate cancer

Each of the three most common contemporary treatments for localized prostate cancer, radical prostatectomy, external beam radiotherapy, and brachytherapy, can have adverse effects on sexual health. Sexual health outcome can be improved by treatment-specific factors, such as the use of nerve-sparing technique during radical prostatectomy, or worsened by the use of androgen deprivation before external beam radiotherapy or brachytherapy. Contemporary studies that have used validated questionnaires to evaluate multiple components of patient-reported sexuality following prostate cancer treatments provide benchmarks of sexual outcome expectations that are of interest to patients selecting their prostate cancer treatment.     

放射性125I粒子组织间植入或联合放化疗治疗复发直肠癌

目的探讨超声或CT引导下放射性125I粒子组织间植入治疗复发直肠癌的技术可行性、近期疗效和副反应.方法 15例直肠癌术后盆腔复发患者,女4例,男11例.硬膜外麻醉,2例经阴道超声引导,13例CT引导,行放射性125I粒子植入术.肿瘤匹配周边剂量为90～110 Gy,每颗粒子活度为0.50～0.70 mCi,植入33～70颗.术后24～48 h拍胸、盆腔X线片了解粒子是否发生移位.术后6例加三维适形放疗,4～6野/次,200～300 cGy/次,5次/周,总剂量为4 500～5 000 cGy,间隔4周.2例粒子治疗后加草酸铂、5-氟尿嘧啶和四氢叶酸化疗1个周期,随访3～15个月,根据CT扫描结果判断肿瘤大小. 结果术后平均7天疼痛缓解,其中12例完全缓解,2例部分缓解,1例无变化,有效率93%(14/15).9例肿瘤完全缓解,2例部分缓解,4例局部进展,局部控制率73%(11/15).2例术后6个月和12个月时死于肺转移.1例1颗粒子移位至盆壁,随访12个月无症状.无治疗相关并发症和副作用发生. 结论经超声或CT引导放射性125I粒子植入治疗复发直肠癌具有安全、微创、并发症发生率低和疗效肯定等优势,粒子治疗后应配合外放疗和全身化疗,有望进一步提高疗效.     

Role of nerve-sparing radical prostatectomy for clinical stage B2 prostate cancer.

To examine the role of nerve-sparing radical prostatectomy in patients with clinical stage B2 prostate cancer we reviewed the first 77 such patients in our series since we adopted the nerve-sparing technique. A total of 47 patients (61%) underwent bilateral and 26 (34%) underwent unilateral nerve-sparing prostatectomy, while in 4 (5%) both neurovascular bundles were resected. Among the patients followed for 12 months 27 of 41 (66%) treated with bilateral and 7 of 19 (37%) treated with unilateral nerve-sparing prostatectomy had potency preserved. With the strict clinicopathological criteria of organ-confined tumor, that is intracapsular tumor with negative surgical margins and undetectable postoperative prostate specific antigen levels, complete tumor excision was achieved in 17 patients (36%) treated with bilateral and 7 of 26 (27%) treated with unilateral nerve-sparing prostatectomy. All patients in whom both neurovascular bundles were resected had pathological stage C or D1 disease. Of the 24 patients who had complete tumor excision by the strict criteria only 15 (19.5% of the 77 preoperatively potent patients) had potency preserved. Of these patients 19 had microscopically positive margins without seminal vesicle invasion (pathological stage C1) with undetectable postoperative prostate specific antigen levels. In addition, 4 patients had seminal vesicle involvement with negative surgical margins and undetectable postoperative prostate specific antigen levels. If these patients also are considered as having complete tumor excision, there was an over-all complete tumor excision rate of 61% (47 of 77), of whom 25 (32% of the 77 patients) had preservation of potency. Ten patients with clinical stage B2 tumor whose potency was preserved had histological and serological evidence of incomplete tumor excision. Of 53 patients with pathological stage C1 disease 9 (17%) had margins positive only in the regions of the neurovascular bundles. Preoperative prostate specific antigen and acid phosphatase levels, and findings on transrectal ultrasonography failed to predict accurately which patients had extracapsular tumor extension. Patients with poorly differentiated tumors and/or bulky disease on rectal examination had a higher incidence of extracapsular extension and positive margins. We conclude that in the majority of potent patients with clinical stage B2 prostate cancer not all of the goals of nerve-sparing radical prostatectomy are realized.(ABSTRACT TRUNCATED AT 400 WORDS)     

125I放射性粒子植入治疗C期激素难治性前列腺癌

目的 探讨125 I放射性粒子植入治疗C期激素难治性前列腺癌的临床疗效.方法 本组11例,均通过前列腺穿刺活检确诊为前列腺癌,Gleason评分6～9分,经内分泌治疗后确认进展为激素难治性前列腺癌时平均PSA为10.91ng/ml,临床分期均为C期,行直肠B超引导下,经会阴穿刺植入放射性125 I粒子治疗.结果 全组患者手术顺利,手术时间30～70min,平均植入粒子49粒,均于术后3～6d出院.术后随访3～71个月,平均31个月.完全有效3例,部分有效1例,病情稳定3例,无效3例,失访1例,PSA无进展生存率70%(7/10).无效患者3例中,2例PSA无进展生存期达2年以上,所有患者术后均未出现严重并发症.结论 125 I放射性粒子植入治疗C期激素难治性前列腺癌安全、有效.