前列腺癌近距离照射联合外照射与单纯外照射疗效与安全性Meta分析

目的 系统评价近距离照射(BT)联合外照射(EBRT)与单纯EBRT对前列腺癌的疗效和安全性。方法 通过计算机检索Pubmed、Web of science、Cochrane Library、CNKI、万方和维普数据库中EBRT联合BT与单纯EBRT治疗前列腺癌的比较实验,检索时间均从建库至2018年7月,按照纳入和排除标准对纳入研究进行资料提取、方法学质量评价后,采用RevMan5.3软件进行Meta分析。结果 共纳入10项研究(含6篇RCT,4篇非RCT),共23393例患者。中危3、5年无生化进展生存率(b-PFS)OR值分别为2.03(95%CI为1.11~3.73,P=0.02)、2.27(95%CI为1.49~3.45,P<0.01),EBRT+BT组优于EBRT组;高危3、5年b-PFS、5年总生存率和5年无转移生存率两组相近。泌尿生殖道≥2、≥3级急性和慢性不良反应OR值分别为1.44(95%CI为1.1~1.38,P<0.01)、3.06(95%CI为1.37~6.80,P<0.01)和1.75(95%CI为1.14~2.69,P=0.01)、3.41(95%CI为2.42~4.82,P<0.01),EBRT组均优于EBRT+BT组;胃肠道不良反应两组相近。结论 BT联合EBRT较单纯EBRT能改善中危前列腺癌患者3、5年b-PFS,但同时也增加了泌尿生殖道不良反应发生率。     

Prostate-specific antigen and external beam radiation therapy in prostate cancer.

This study of 133 patients with localized prostate cancer (Stages A2 to C), treated by external beam radiation therapy (XRT), was undertaken for two reasons: (1) to investigate the usefulness of pretreatment serum prostate-specific antigen (PSA) levels in evaluating patients before XRT; and (2) to investigate post-XRT changes in PSA values and their likely clinical significance. It was found that pretreatment PSA values in patients with localized disease exhibit wide patient to patient variability with a greater than 100-fold difference between the lowest and highest values. Although mean PSA values were significantly higher in Stage C disease (51 patients; mean PSA, 17.3 ng/ml) than in Stage A2 disease (31 patients; mean PSA, 9.0 ng/ml), Stage B1 disease (23 patients; mean PSA, 9.1 ng/ml), or Stage B2 disease (28 patients; mean PSA, 10.6 ng/ml), individual values were of virtually no help in assigning individual patients to a clinical stage. PSA levels did not correlate with grade. After XRT, PSA values fell significantly and dramatically in virtually all patients (98%) by 3 months follow-up. Mean PSA fell from 12.5 to 2.6 ng/ml, and median PSA fell from 6.6 to 1.9 ng/ml. In most patients, PSA continued to fall up to 12 months after XRT and then stabilized at 21 months. Although PSA values fell dramatically after XRT, PSA was detectable in the serum of all patients. PSA values tended to transiently and mildly elevate during XRT. In a small proportion of patients, rising PSA values were observed after 6 months. The full significance of this requires further follow-up, of four such patients, one has relapsed. PSA is a more sensitive marker of prostatic radiation than prostatic acid phosphatase.     

The role of external beam radiation therapy after prostatectomy for prostate cancer

The role of radiation therapy as an adjuvant to prostatectomy is evaluated in 21 patients. Eleven were treated prior to clinical recurrence with 100% local control, no serious complications, and 86% long-term survival. Ten were treated after local recurrence with 80% local control, no serious complications, and 71% long-term survival. These data and the available literature indicate that the patient found to have capsular penetration, seminal vesicle involvement, or positive surgical margins at prostatectomy can be salvaged by postsurgical radiation therapy. When this is done after recovery from surgery, rather than waiting for clinical recurrence, a lower radiation dose can be used (6000 rad vs. 7000 rad), improved local control is obtained (94% vs. 79%), and fewer serious complications are observed.     

External beam radiation therapy for prostate cancer

Men with non-metastatic prostate cancer have many treatment options. For over 35 years, radiation therapy has been a mainstay of treatment for this disease. With improvements in technology and better use of pretreatment prognostic factors, such as prostate specific antigen level and Gleason score, biochemical and clinical results have steadily improved. This article reviews the current status of radiation therapy in the treatment of prostate cancer. Results of treatment utilizing three-dimensional conformal and conventional techniques are compared and contrasted. The appropriate use of adjuvant hormones and particle beam therapy in the management of this disease is also discussed. Finally, the toxicity and future directions of radiation therapy in the treatment of prostate cancer are addressed.     

Family history of prostate cancer and relapse after definitive external beam radiation therapy

PURPOSE: The influence of family history on outcome after definitive therapy for prostate cancer has been disputed. One series reported increased relapse rates in men with a positive family history of prostate cancer treated with radical prostatectomy or radiation therapy, whereas others have reported no difference in outcome. We examined our series of patients treated with definitive external beam radiation therapy to determine if a positive family history for prostate cancer is associated with better or worse outcome. METHODS AND MATERIALS: Family history information was available for 538 patients treated with radiation therapy for prostate cancer between 1983 and 2001. Prostate cancer in one or more first-degree relatives (father, brother, or son) was considered a positive family history. The endpoint of interest was time to prostate-specific antigen failure or initiation of hormonal therapy after radiation therapy. RESULTS: Ninety-seven of 538 patients (18%) had a positive family history. There were no significant differences between the positive and negative family history groups. Family history had no effect on relapse-free survival rates in the entire cohort (p = 0.94) or in any subgroup. African American patients with a positive family history had significantly worse 5-year relapse-free survival rates, although there were few patients in this subgroup. Neither family history nor race was a statistically significant predictor of relapse in multivariate analysis; however, combined African American race and positive family history was associated with worse relapse-free survival rates. CONCLUSIONS: In this large study of patients receiving definitive radiation therapy for localized prostate cancer, no relationship was found between positive first-degree family history of prostate cancer and relapse. The influence of family history on clinical outcome may be more understandable once the gene or genes responsible for hereditary prostate cancer are identified.     

Whole-gland salvage high-intensity focused ultrasound therapy for localized prostate cancer recurrence after external beam radiation therapy

BACKGROUND:

Whole‐gland high‐intensity focused ultrasound (HIFU) has been used as salvage therapy for local recurrence following external beam radiation therapy for decades. This article describes the use of the Sonablate 500 HIFU system in the salvage setting.

METHODS:

An evaluation was performed of a consecutive group of men with biochemical failure after external beam radiation therapy with histologically proven local recurrence and bone‐scan and pelvic magnetic resonance imaging to exclude macroscopic metastases, and who chose to have whole‐gland salvage HIFU (Sonablate 500) at 2 centers (3 expert HIFU surgeons at each center). The modified Clavien system was used to categorize adverse events and validated questionnaires for functional outcomes. Progression following HIFU treatment was defined as ASTRO‐Phoenix criteria (prostate serum antigen [PSA] >nadir+2 ng/mL) and/or a positive biopsy and/or start of hormone therapy.

RESULTS:

Eighty‐four men underwent whole‐gland salvage HIFU (2004‐2009). Median age, pretreatment serum PSA, and biopsy Gleason score was 68 years (range, 64‐72 years), 4.3 ng/mL (range, 1.9‐7.9 ng/mL), and 7 (range, 6‐7), respectively. Mean follow‐up was 19.8 months (range, 3.0‐35.1 months). After salvage HIFU, 62% of the men were pad‐free and leak‐free. Mean International Index of Erectile Function‐5 point score fell from 8.8 to 4.7 (P < .001). International Prostate Symptoms Score and RAND‐SF36 scores were not affected. Two men developed rectourethral fistulae after 1 salvage procedure. A further 2 fistulae occurred in the 6 men undergoing a second salvage HIFU. Intervention for bladder outlet obstruction was needed in 20% (17 of 84 patients). If PSA nonresponders were included, 1‐ and 2‐year progression‐free survival rates were 59% (50 of 84 patients) and 43% (36 of 84 patients), respectively. If PSA nonresponders were excluded, 1‐ and 2‐year progression‐free survival rates were 62% (48 of 77 patients) and 48% (37 of 77 patients), respectively.

CONCLUSIONS:

Salvage whole‐gland HIFU is a high‐risk procedure. Although its use in early cancer control is promising, strategies to better identify metastatic disease prior to salvage therapy and reduce local toxicity are needed to improve on this. Cancer 2012;118: 3071–78. © 2011 American Cancer Society.     

Modeling positioning uncertainties of prostate cancer external beam radiation therapy using pre-treatment data

Purpose

To investigate the influence of treatment plan data and image guidance (IG) on positioning uncertainty during prostate cancer (PCa) radiotherapy (RT).

Methods

Body mass index (BMI), planning target volume (PTV), bladder volume (BV), and rectal cross section area (RCS) were collected for 267 consecutive PCa patients undergoing daily IGRT. Radiographic isocenter corrections to intra-prostatic fiducials for 12,490 treatment fractions were used to derive random (RE) and systematic (SE) inter-fraction uncertainties for the cardinal axes. These data were used to simulate RE and SE for weekly IG and Action Level (AL)-IG treatment protocols.

Results

SE and RE were 2–5 and 3–4 mm in the cardinal axes, respectively, during simulation of no IG. Without IG, positive correlations (p < 0.01) were noted for (1) anterior-posterior RE vs. RCS and BV and (2) cranio–caudal RE vs. RCS, BV and BMI. The RE increase was 3 mm for the highest quartile of RCS, BV and BMI. Daily IGRT eliminated this relationship. 3D IG corrections of 1 cm or more occured in 27% of treatment fractions and in 97% of patients.

Conclusion

PCa patients with elevated pre-treatment BV, RCS and BMI have increased inter-fractionation positioning uncertainty and appear the primary candidates for daily IGRT.     

Clarity系统在前列腺癌体外放射治疗中的研究进展

体外放射治疗（EBRT）是前列腺癌的主要治疗手段之一,而在图像引导下实施EBRT更切合精准放疗策略。Clarity系统作为一种新型图像引导技术,已在临床实践中应用于前列腺癌EBRT的实时跟踪,在提升EBRT靶向精准性的同时,也显著降低了传统EBRT的不良反应。本文就Clarity系统在前列腺癌EBRT中的应用及其存在的问题进行系统阐述。     

Clarity系统在前列腺癌体外放射治疗中的研究进展北大核心CSCD

体外放射治疗(EBRT)是前列腺癌的主要治疗手段之一,而在图像引导下实施EBRT更切合精准放疗策略。Clarity系统作为一种新型图像引导技术,已在临床实践中应用于前列腺癌EBRT的实时跟踪,在提升EBRT靶向精准性的同时,也显著降低了传统EBRT的不良反应。本文就Clarity系统在前列腺癌EBRT中的应用及其存在的问题进行系统阐述。     

The relationship between technical parameters of external beam radiation therapy and complications for localized prostate cancer

BACKGROUND: This study was performed to review retrospectively the clinical course of chronic rectal bleeding as a complication of external beam radiation therapy for localized prostate cancer and to analyze the relationship between technical parameters of radiation therapy and the complications. METHODS: Seventy-one patients with stages A2, B and C were treated with local-field radiotherapy (total dose 52.5-66 Gy, daily dose 2.0-3.28 Gy, field area 30-81 cm2, number of fields 3-15 ports, planning simulations X-ray or CT-based) between 1989 and 1998 at three institutions. The protocols were consistent during this same period at these institutions. RESULTS: Multivariate analysis revealed pretreatment PSA and Gleason sum to be statistically significant predictors of 5 year prostatic specific antigen (PSA) relapse-free rates in a median follow-up period of 42 months (range 12-119 months). The significant risk factors for higher grading of acute morbidity were a biological equivalent dose, alpha/beta = 10(BED10) > or =65 Gy, dose per fraction > or =3.0 Gy, field area > or =42 cm2, fewer ports and X-ray planning simulation. However, no parameter was associated with higher grading of late morbidity. Eleven patients (15.4%) experienced a late GI complication: grade 1 (4.2%), grade 2 (9.8%), grade 3 (1.4%). The median time to occurrence of rectal bleeding was 12 months after radiotherapy and the mean duration of morbidity was 11 months. CONCLUSIONS: Higher total dose and dose per fraction, larger field area, fewer ports and X-ray simulation increased the grades of acute morbidity. A majority of chronic rectal bleedings were transient and responded to conservative treatment.     

Improving the preservation of erectile function after external beam radiation therapy for prostate cancer.

BACKGROUND AND PURPOSE: To investigate whether the type of collimation technique, target dose and treated volume influence the prevalence of intact erectile function after external beam radiation therapy for localized prostate cancer. PATIENTS AND METHODS: A prospective study was conducted to assess erection stiffness before treatment and after follow-ups of 9-18 months and 4-5.5 years. Information was collected using the Radiumhemmet Scale of Sexual Function. RESULTS: Thirty-one men were 'potent' before the radiation. Fourteen of them were treated with a conventional collimator and 17 were given three-dimensional conformal therapy with the aid of a multileaf collimator. Preserved erectile function at 9-18 months was found in 17 of the 31 men (55%) and at the 4-5-year follow-up in five of 22 (23%). Preservation of potency was related to the treatment procedure but not to the treatment volume. CONCLUSIONS: Conformal therapy may increase the percentage of men preserving erectile function during radiotherapy for localized prostate cancer; it is possible that the differences to conventional therapy do not depend on treated volume.     

Long-term symptoms after external beam radiation therapy for prostate cancer with three or four fields

The aim of this study was to investigate whether external beam radiation treatment with three or four fields affects the risk of long-term distressful symptoms. The study included 145 patients who had been treated in Stockholm from 1993 to 1996 for localized prostate cancer. Bowel, urinary and sexual function as well as symptom-induced distress were assessed by means of a postal questionnaire 29-59 months after therapy. Among patients treated with a multileaf collimator, defecation urgency, diarrhoea and loose stools were more common after four fields than after three fields, but faecal leakage necessitating the use of pads and distress from the gastrointestinal tract were less common (although not statistically significantly so). Among bowel symptoms, the strongest association with gastrointestinal distress was found for faecal leakage. Three fields without a multileaf collimator entailed a higher risk of defecation urgency than three fields with a multileaf collimator. We conclude that the choice of three or four fields may imply a contrasting risk scenario for defecation urgency or diarrhoea in comparison with faecal leakage.     

High-dose external beam radiation for localized prostate cancer: current status and future challenges

Since the 1960s, external beam radiation has been one of the major curative treatment options for patients with clinically localized prostate cancer. Efforts to improve the efficacy of this modality have focused on delivering a higher dose, and several recent randomized trials have confirmed that this higher dose results in improved oncological outcomes, particularly for patients with intermediate-risk disease. Technological advancements over the past 2 decades have allowed highly conformal treatments that spare more normal tissue and reduce early and long-term treatment side effects. In a complementary fashion, methods have been developed for better real-time localization of the prostate such that radiation fields can be shifted before each treatment to match the daily shifts in the position of the target, leading to greater accuracy and allowing for smaller treatment margins that in turn will overlap with less normal tissue. With newer and more expensive technologies such as intensity-modulated radiation therapy and protons being used with increasing frequency for the treatment of prostate cancer, it becomes imperative to study the risks and benefits of each new modality so that informed cost-benefit decisions can be made. Similarly, there has been a growing interest in hypofractionation as a means of exploiting the supposed low alpha/beta ratio of prostate cancer to shorten overall treatment time and thereby improve convenience and lower costs. However, as with any new technology, it is necessary to proceed with caution in the arena of hypofractionation while we await the results of trials that will help us to determine the long-term risks and benefits of hypofractionation and whether biological assumptions about the underlying alpha/beta ratio can translate into a true clinical advantage.     

PSA doubling time kinetics during prostate cancer biochemical relapse after external beam radiation therapy

PURPOSE: To investigate whether prostate-specific antigen PSA doubling time (PSADT) is constant in men with biochemical prostate cancer relapse after external beam radiotherapy (EBRT). METHODS AND MATERIALS: A total of 513 men treated radically with EBRT, with or without androgen ablation (AA), between 1993 and 2000, developed biochemical relapse. The slope of the ln (PSA) vs. time graph is calculated for the first two values after PSA nadir (first slope), the last two recorded PSAs (last slope), and all values excluding the first and final PSA (mid slope). Differences in these slopes were compared statistically with subgroup analysis for AA and secondary intervention. RESULTS: For men treated with EBRT and AA first slope was faster than either mid slope (p = 0.031) or last slope (p < 0.001). Men treated with EBRT alone had no change in PSADT over time unless they subsequently received secondary intervention. This group had a more rapid last slope compared with mid slope (p < 0.001). CONCLUSIONS: PSA initially rises more rapidly after AA cessation, probably because of testosterone recovery. A subgroup of patients, who received secondary intervention after treatment with radiotherapy alone, showed a change in PSADT, to a faster velocity. This greater than constant exponential PSA growth is presumably the catalyst for secondary intervention. Otherwise, PSADT did not change during prostate cancer biochemical relapse.     

The impact of geometric uncertainty on hypofractionated external beam radiation therapy of prostate cancer

PURPOSE: Recent publications indicate alpha/beta for prostate carcinoma could be lower than assumed. Therefore, hypofractionation might increase the therapeutic ratio. However, patient repositioning and organ motion may affect hypofractionated treatments more than conventional treatments. Our purpose is to evaluate the potential impact of geometric uncertainties on hypofractionated treatments. METHODS AND MATERIALS: Tumor control probability (TCP) and normal tissue complication probability (NTCP) are calculated for simulated conventional and hypofractionated treatments, assuming alpha/beta of 1.5 Gy for prostate and 3.0 Gy for rectum. A Monte Carlo simulation randomly samples systematic and random displacements and produces the cumulative dose distribution for the prostate and rectum. The limiting number of fractions and the impact of different alpha/beta values are also explored. RESULTS: A consistent but small reduction in TCP is seen with hypofractionation (generally <1%) as a result of geometric uncertainties. Escalated hypofractionation seems to allow large TCP gains ( approximately 20%) without increasing NTCP. Treatments of five fractions seem to affect outcome minimally. The alpha/beta value has a much greater impact on TCP than geometric uncertainties. CONCLUSION: The potential increased influence of geometric uncertainties on hypofractionation seems small. Limited knowledge of radiobiologic response is likely a greater obstacle to prostate hypofractionation than geometric uncertainties.     

Salvage therapy for locally recurrent prostate cancer after external beam radiotherapy

Opinion statement The greatest obstacle in the cure of patients with locally recurrent prostate cancer after radiation therapy is the lack of early detection markers. The majority of patients who are candidates for local salvage therapy have locally advanced disease, precluding successful salvage therapy. A low pretreatment prostate specific antigen (PSA) has shown to be a favorable prognostic variable for disease progression, regardless of the specific local salvage therapy used. Of all the local salvage treatment options for these patients, we believe that salvage radical prostatectomy (RP) offers patients the great-est likelihood of a cure. The salvage RP results approach those achieved with standard RP for patients of similar pathologic stage. When patients are treated early in the course of recurrent disease (preoperative PSA < 10 ng/mL), an estimated two-thirds of patients will be disease-free 5 years after salvage RP alone. With better patient selec-tion and continued technical modifications, the morbidity associated with salvage RP has substantially improved. Perioperative complications approach those observed with standard RP and approximately two-thirds of patients will recover urinary continence. Select patients may also recover functional erections when nerve-sparing techniques are used. Salvage cryotherapy and brachytherapy are minimally invasive alternatives to salvage RP. The cancer control results of these procedures appear to be inferior to results achieved with salvage RP. Each of these procedures is associated with signifi-cant morbidity and do not appear to provide a clear advantage over salvage RP in terms of posttreatment complications, urinary continence, and erectile function. A long-term cure is possible for patients with locally recurrent prostate cancer after radiation therapy. Local salvage therapy must be instituted early to be successful in the course of progressive disease.     

Post-irradiation sarcoma after external beam radiation therapy for localized adenocarcinoma of the prostate

We report a case of postirradiation sarcoma that arose in the right inguinal region 8 years after completion of external beam radiation therapy for a localized adenocarcinoma of the prostate. The patient was treated in 1995 with a "mixed-beams" technique (18 MV photons and 65 MeV fast neutrons). Eight years after the end of treatment, he presented with a radio-induced, high-grade spindle-cell sarcoma. Cytogenetic analysis was performed to confirm the diagnosis. Although the use of external beam radiation therapy for the treatment of prostate cancer has been common practice for decades, postirradiation sarcomas have been reported to be rare sequelae of irradiation and, to our knowledge, only a few of them were cytogenetically investigated.