Prediction of radial distance of extraprostatic extension from pretherapy factors

PURPOSE: Extraprostatic extension (EPE) of tumor conveys an adverse prognosis in early-stage prostate cancer. Previous studies reported on the linear and radial distance of EPE (EPEr) as measured from the prostate edge. In this study, the correlation of the EPEr from a large whole mount prostatectomy series was determined with respect to the needle biopsy and prostatectomy specimen findings. METHODS AND MATERIALS: In a 24-month period, 404 patients underwent radical prostatectomy and the specimens were whole mounted. The preoperative records, biopsy findings, and EPEr from these specimens were evaluated. RESULTS: The range of the EPEr distance was 0.0-5.7 mm. A three-category model was used that included 283 patients (70%) with no EPE, 59 (15%) with "near EPE" (range, 0.01-0.59 mm), and 62 (15%) with "far EPE" (>or=0.6 mm). Univariate analysis revealed that patient age and prostate volume did not correlate with EPEr, in contrast to all other factors evaluated. Multivariate analysis identified the preoperative serum prostate-specific antigen, the percentage of cancer in the biopsy cores, and clinical tumor stage as significant. However, the Gleason score was not associated with the EPEr. Greater discrimination was possible in estimating the probability of extension in the "near" category than in the "far" category. CONCLUSION: EPEr is associated with the preoperative prostate-specific antigen level, percentage of cancer in the biopsy cores, and clinical tumor stage. These data might be useful in planning local therapies for prostate cancer, but additional studies identifying factors associated with EPEr beyond 3-5 mm could have relevance regarding the appropriate radiotherapeutic management strategies.     

Correlation of margin status and extraprostatic extension with progression of prostate carcinoma.

BACKGROUND: The correlation of surgical margins and extraprostatic extension (EPE) with progression is uncertain with regard to prostate carcinoma patients treated by radical prostatectomy. The objective of this study was to define factors predictive of cancer progression; emphasis was placed on surgical margins and their relation to extraprostatic extension. METHODS: The study group consisted of 377 patients who were treated by radical retropubic prostatectomy and bilateral pelvic lymphadenectomy at the Mayo Clinic between 1986 and 1993. All specimens were totally embedded and whole-mounted. Patients ranged in age from 41 to 79 years (mean, 65 years). Those with seminal vesicle invasion or lymph node metastasis and those treated preoperatively with radiation or androgen deprivation were excluded. Final pathologic T classifications were pT2a (41 patients), pT2b (237), and pT3a (99). Progression was defined as biochemical failure (prostate specific antigen [PSA] >0.2 ng/mL), clinical or biopsy-proven local recurrence, or distant metastasis. The mean follow-up was 5.8 years (range, 0.2-11.4 years). Seventy-nine patients who received adjuvant treatment within 3 months after surgery were excluded from survival analysis. RESULTS: The overall margin positivity rate was 29%. Seventy-two patients (19%) had only positive surgical margins without evidence of EPE ("surgical incision"), 53 (14%) had only EPE, 37 (10%) had both, and 215 (57%) had neither. Positive margins were correlated with the finding of EPE (P = 0.003). Progression free survival rates at 5 and 10 years were 88% and 67%, respectively. In univariate analysis, preoperative PSA concentration, positive surgical margins, Gleason grade, cancer volume, and DNA ploidy were significant in predicting progression (P values, <0.001, <0.001, 0.01, 0.007, and <0.001, respectively). In multivariate analysis, margin status and DNA ploidy were independent predictors of progression (relative risk for margin status, 1.9; 95% confidence interval [CI], 1.1-3.4; P = 0.03; relative risk for DNA ploidy, 5.1; 95% CI, 2.4-10.9; P<0.001). Among patients with positive margins, 5-year progression free survival was 78% for those with negative EPE and 55% for those with positive EPE. CONCLUSIONS: Surgical margin status and DNA ploidy were independent predictors of progression after radical prostatectomy. To improve cancer control, adjuvant therapy may be considered for patients with positive surgical margins or nondiploid cancer.     

Palladium-103 brachytherapy for prostate carcinoma

PURPOSE: A report of biochemical outcomes for patients treated with palladium-103 (Pd-103) brachytherapy over a fixed time interval. METHODS AND MATERIALS: Two hundred thirty patients with clinical stage T1-T2 prostate cancer were treated with Pd-103 brachytherapy and followed with prostate-specific antigen (PSA) determinations. Kaplan-Meier estimates of biochemical failure on the basis of two consecutive elevations of PSA were utilized. Multivariate risk groups were constructed. Aggregate PSA response by time interval was assessed. RESULTS: The overall biochemical control rate achieved at 9 years was 83.5%. Failures were local 3.0%; distant 6.1%; PSA progression only 4.3%. Significant risk factors contributing to failure were serum PSA greater than 10 ng/ml and Gleason sum of 7 or greater. Five-year biochemical control for those exhibiting neither risk factor was 94%; one risk factor, 82%; both risk factors, 65%. When all 1354 PSA determinations obtained for this cohort were considered, the patients with a proportion of PSAs < or = 0.5 ng/ml continued to increase until at least 48 months post-therapy. These data conformed to a median PSA half-life of 96.2 days. CONCLUSIONS: Prostate brachytherapy with Pd-103 achieves a high rate of biochemical and clinical control in patients with clinically organ-confined disease. PSA response following brachytherapy with low-dose-rate isotopes is protracted.     

放射性粒子组织间近距离治疗早期前列腺癌

前列腺癌治疗包括根治性手术、外放疗和组织间近距离治疗。组织间近距离治疗由于具有局部剂量高和副作用轻而易于被患者接受,目前已经成为美国早期前列腺癌的标准治疗手段之一。本文综述了前列腺癌近距离治疗的历史、技术方法、适应证和并发证。     

Radioactive seed migration to the chest after transperineal interstitial prostate brachytherapy: extraprostatic seed placement correlates with migration

PURPOSE: To examine the incidence of seed migration detected on chest X-ray and to identify the predictors associated with its occurrence. METHODS AND MATERIALS: Between May 1998 and April 2000, 102 patients underwent permanent prostate brachytherapy at our institution and 100 were eligible for the study. Chest X-rays obtained at follow-up were examined for the number and location of seeds. The patient and treatment variables potentially associated with the occurrence and number of seed migrations were analyzed. RESULTS: One or more seeds were identified on the chest X-rays of 55 (55%) of 100 patients. The mean number of intrathoracic seeds in patients with migration was 2.2 (range, 1-10), and the proportion of seeds that migrated to the thorax was 0.98%. The rate of extraprostatic seeds planned was 43.9%, and postimplant CT identified 37.9% in such a location. The number of seeds planned for extraprostatic placement and below the apex were statistically significant (alpha = 0.05) predictors in univariate logistic analysis. Multivariate analysis revealed the planned number of extraprostatic seeds as the only statistically significant predictor (p = 0.04). CONCLUSION: Extraprostatic placement of loose seeds is associated with an increased likelihood for, and frequency of, seed migration to the thorax. Nonetheless, the small proportion of implanted seeds that migrated (相似文献   

Local anesthesia for prostate brachytherapy.

PURPOSE: To demonstrate the technique and feasibility of prostate brachytherapy performed with local anesthesia only. METHODS AND MATERIALS: A 5 by 5 cm patch of perineal skin and subcutaneous tissue is anesthetized by local infiltration of 10 cc of 1% lidocaine with epinephrine, using a 25-gauge 5/8-inch needle. Immediately following injection into the subcutaneous tissues, the deeper tissues, including the pelvic floor and prostate apex, are anesthetized by injecting 15 cc lidocaine solution with approximately 8 passes of a 20-gauge 1.0-inch needle. Following subcutaneous and peri-apical lidocaine injections, the patient is brought to the simulator suite and placed in leg stirrups. The transrectal ultrasound (TRUS) probe is positioned to reproduce the planning images and a 3.5- or 6.0-inch, 22-gauge spinal needle is inserted into the peripheral planned needle tracks, monitored by TRUS. When the tips of the needles reach the prostatic base, about 1 cc of lidocaine solution is injected in the intraprostatic track, as the needle is slowly withdrawn, for a total volume of 15 cc. The implants are done with a Mick Applicator, inserting and loading groups of two to four needles, so that a maximum of only about four needles are in the patient at any one time. During the implant procedure, an additional 1 cc of lidocaine solution is injected into one or more needle tracks if the patient experiences substantial discomfort. The total dose of lidocaine is generally limited to 500 mg (50 ml of 1% solution). RESULTS: To date, we have implanted approximately 50 patients in our simulator suite, using local anesthesia. Patients' heart rate and diastolic blood pressure usually showed moderate changes, consistent with some discomfort. The time from first subcutaneous injection and completion of the source insertion ranged from 35 to 90 minutes. Serum lidocaine levels were below or at the low range of therapeutic. There has been only one instance of acute urinary retention in the patients treated so far, and no unplanned admissions to the hospital or need to reschedule a patient to be implanted under general or spinal anesthesia. CONCLUSIONS: The substitution of local anesthesia has facilitated rapid introduction of a high-volume brachytherapy program at an institution that previously had none, without requiring the allocation of significant operating room time. Although the patients reported here were implanted without conscious sedation, we are starting to try various sedatives and analgesics for patients who we anticipate will have substantial anxiety with the procedure.     

The clinical significance and therapeutic implications of extraprostatic invasion

Invasion of the prostatic margin by cancer establishes a higher risk of disease progression and treatment failure depending upon its extent and other clinical factors. Pathological stage is the most important single prognostic indicator, but determined reliably only in patients having radical prostatectomy. Tumour beyond the prostatic margin or its invasion into the seminal vesicle defines the local stage category as T3, and when confirmed by pathological examination the extent of prostatic margin involvement has prognostic significance. Prediction of extraprostatic invasion may influence therapeutic decisions, but can be difficult to determine for the individual patient prior to treatment. In some individuals having radical prostatectomy, the finding of extraprostatic invasion is unsuspected, and fortunately for the majority of these men the treatment remains curative. On the other hand, when extraprostatic invasion is suspected prior to or at surgery, wide excision may be necessary to achieve negative surgical margins, with other factors contributing independently to the likelihood of subsequent progression. Radiotherapy is an effective alternative treatment for clinical stage T3 and high-risk clinically localized cancer. Recent technological advances and use of combination modality treatment with radiation and hormone manipulation have improved survival outcomes and reduced side-effects. Radiation also has its place as adjuvant treatment following radical prostatectomy in high-risk disease, or as salvage following PSA recurrence, with ongoing trials evaluating potential benefit and toxicity. For clinically localised stage T3 prostate cancer, treatment with surgery or radiotherapy may be highly effective, but multimodality interventions are increasingly being used for primary treatment where clinical assessment indicates that there would otherwise be a high risk for disease progression and therapeutic failure.     

The role of external beam radiotherapy with I-125/Pd-103 brachytherapy for prostate carcinoma.

BACKGROUND AND PURPOSE: To compare the biochemical outcomes of patients treated with Pd-103/I-125 brachytherapy alone vs. brachytherapy combined with external beam radiotherapy for early stage prostate carcinoma. METHODS: Brachytherapy monotherapy was used in 403 patients. Brachytherapy was combined with 45 Gy of external beam radiotherapy in 231 patients. Median follow-up was 58 months. To compare the biochemical outcomes of these two treatment approaches, patients were stratified into three relative risk groups: low risk, T(1)-T(2), Gleason 2-6/10, PSA< or =10.0; intermediate risk, T(3), Gleason 7-10/10, PSA>10.0 (one factor); high risk, T(3), Gleason 7-10/10, PSA>10.0 (two factors). RESULTS: The actuarial biochemical progression-free rate (bNED) for the entire 634 patients was 85% at 10 years. The bNED outcomes by risk group for monotherapy vs. combined therapy respectively were: low risk, 94 vs. 87%; intermediate risk, 84 vs. 85%; high risk, 54 vs. 62%. These differences did not reach statistical significance for any risk group. Rectal morbidity was slightly greater in the combined treatment patients. CONCLUSION: Although the addition of external beam irradiation to brachytherapy is conceptually appealing for patients with higher risk prostate carcinoma, we were unable to demonstrate a benefit. Whether this is because of patient selection biases within the risk groupings, an artefact of retrospective review, or because external radiotherapy does not offer additional benefit is uncertain.     

The relevance of prostatectomy findings for brachytherapy selection in patients with localized prostate carcinoma

BACKGROUND: The efficacy of brachytherapy for patients with localized prostate carcinoma depends on adequate radiotherapeutic coverage of the primary tumor and its subclinical extraprostatic extensions. Predictive models based on pretherapy factors may be useful to estimate the likelihood for clinically relevant extraprostatic disease and may be incorporated into selection criteria for this procedure. METHODS: Multivariate logistic regression model building was performed using pretherapy factors in 2905 surgically staged patients with localized prostate carcinoma to estimate the probability of seminal vesicle and/or lymph node involvement. Bootstrap methods were employed to assess the stability of the final model parameters and to determine the sensitivity and specificity of the final model. RESULTS: Clinical tumor classification, biopsy Gleason score groupings, and serum prostate specific antigen (PSA) levels were associated with seminal vesicle and/or pelvic lymph node involvement. These factors were incorporated into a multivariate model that predicted for these adverse histopathologic features. Allowing for up to a 10% likelihood for seminal vesicle and/or pelvic lymph node involvement, patients with tumors classified as T1c-T2a, Gleason scores of 2-6, and PSA < or = 16 ng/mL; or with tumors classified as T1c-T2a, Gleason scores of 7-10, and PSA < or = 4 ng/mL; or with tumors classified as T2b-T2c, Gleason scores of 2-6, and PSA < or = 6 ng/mL would be potential candidates for brachytherapy alone. CONCLUSIONS: The predictive model presented may provide criteria whereby an adequately performed prostate brachytherapy procedure is expected to encompass the intraprostatic and adjacent extraprostatic disease. Prostate brachytherapy alone may be considered in these circumstances, whereas the addition of external beam radiotherapy may be reserved for patients with disease that is apt to extend beyond the brachytherapy target volume.     

The effect of disease and treatment-related factors on biopsy results after prostate brachytherapy: implications for treatment optimization

BACKGROUND: Posttreatment prostate biopsy is a method of assessing local control after irradiation for prostate carcinoma. An analysis of the effect of disease- and treatment-related factors on biopsy results after prostate brachytherapy was performed to aid in patient selection and treatment optimization. METHODS: Two hundred sixty-eight patients underwent posttreatment prostate biopsy (6-8 cores) 2 years after brachytherapy alone without external beam irradiation. Follow-up ranged from 24 to 111 months (median, 43 months). Implants were performed using a real-time ultrasound guided technique with the isotopes (125)I in 186 and (103)Pd in 82 patients. Ninety-eight patients underwent hormonal therapy (HT) 3 months before and 2-3 months after implant. Implant dose was defined as the D90 (dose delivered to 90% of the gland from the dose volume histogram generated using 1-month computed tomography-based dosimetry). RESULTS: Overall, 89% of patients (238 of 268) had negative biopsies. A positive biopsy was a predictor of biochemical failure. Patients with a positive biopsy had a 5-year freedom from biochemical failure of 40% versus 76% for patients with a negative biopsy (P = 0.0003). Univariate and multivariate analysis found that risk group, HT, and implant dose significantly affected biopsy outcome. Patients with low risk features (prostate specific antigen [PSA] 10 ng/mL or Gleason score >/= 7 or classification T2b or higher) (n = 164) (P = 0.008). Hormonal therapy was associated with a negative biopsy rate of 98% versus 84% for implant alone (P = 0.003). Patients receiving a high implant dose (D90 >/= 140 grays [Gy] for (125)I or >/= 100 Gy for (103)Pd) (n = 174) had a negative biopsy rate of 95% versus 77% for those receiving a low dose (D90 < 140 Gy for (125)I or < 100 Gy for (103)Pd) (n = 87; P < 0.001). CONCLUSIONS: Biopsy results support the use of brachytherapy without external beam irradiation for patients with low risk features and highlight the importance of achieving an adequate implant dose.     

Modern brachytherapy for treatment of prostate cancer.

BACKGROUND: Prostate cancer is the most common cancer diagnosed in men. An increasing number of these patients are seeking minimally invasive procedures such as transperineal interstitial permanent radioactive seed prostate brachytherapy. METHODS: This paper reviews the historical perspective and the current advances in transperineal interstitial permanent radioactive seed prostate brachytherapy. The 10- to 15-year results data now published for brachytherapy alone or in combination with external-beam irradiation are also reviewed. RESULTS: Modern brachytherapy using transperineal interstitial permanent radioactive seed prostate brachytherapy offers patients an excellent quality of life with convenient outpatient treatment with long-term (10- to 15-year) biochemical relapse-free survival rates ranging from 67% to 87%, depending on risk stratification. CONCLUSIONS: Modern-day brachytherapy utilizing either radioactive iodine-125 or palladium-103 alone or in combination with supplemental external-beam treatment offers patients a successful treatment outcome with acceptable toxicity.     

前列腺癌包膜外侵犯对根治性前列腺切除术中性神经保留决策的影响

保留性神经(NS)的根治性前列腺切除术(RP)能够促进术后性功能的恢复,但可能增加术后切缘阳性率与生化复发的风险,尤其是对于存在前列腺癌包膜外侵犯(EPE)的患者。预测EPE是根治性前列腺切除术制定手术方式的关键。文章就术前预测EPE的手段做一综述,以期为临床RP提供依据。     

Isotope selection for patients undergoing prostate brachytherapy.

PURPOSE: Ultrasound-guided transperineal interstitial permanent prostate brachytherapy (TIPPB) is generally performed with either 103Pd or 125I. The use of 125I for low Gleason score tumors and 103Pd for higher Gleason scores has been suggested based on isotope dose rate and cell doubling time observed in in vitro studies. While many centers follow these isotope selection criteria, other centers have elected to use only a single isotope, regardless of Gleason score. No clinical data have been published comparing these isotopes. This study was undertaken to compare outcomes between 125I and 103Pd in a matched pair analysis for patients undergoing prostate brachytherapy. METHODS AND MATERIALS: Six hundred forty-eight consecutively treated patients with clinically confined prostate cancer underwent TIPPB between June 1992 and February 1997. Five hundred thirty-two patients underwent TIPPB alone, whereas 116 received pelvic external beam irradiation and TIPPB. Ninety-three patients received androgen deprivation therapy prior to TIPPB. The prescribed doses for TIPPB were 160 Gy for 125I (pre-TG43) and 120 Gy for 103Pd. Patients treated with combination therapy received 41.4 or 45 Gy (1.8 Gy/fraction) external beam irradiation followed by a 3- to 5-week break and then received either a 120-Gy 125I or a 90-Gy 103Pd implant. Until November 1994, all patients underwent an 125I implant after which the isotope selection was based on either Gleason score (Gleason score 2-5:125I; Gleason 5-8:103Pd) or isotope availability. A matched pair analysis was performed to assess any difference between isotopes. Two hundred twenty-two patients were matched according to Gleason score, prostate-specific antigen (PSA), and stage. PSA relapse-free survival (PSA-RFS) was calculated based on the American Society for Therapeutic Radiology and Oncology (ASTRO) Consensus Group definition of failure. Kaplan-Meier actuarial survival curves were compared to assess differences in pretreatment PSA and Gleason score. RESULTS: Univariate analysis of the 648 patients identified Gleason score, pretreatment PSA value, and stage as significant factors to predict PSA-RFS, but failed to identify isotope selection as significant. To address the significance of isotope selection further, the matched pair groupings were performed. The minimum follow-up for all 222 matched patients is 24 months with a median follow-up of 42 months (24-82). The actuarial PSA-RFS at 5 years for all 222 patients is 86.5%. One hundred eleven of the 222 matched patients received a 103Pd implant with an 87.1% 5-year PSA-RFS. The remaining 111 patients underwent a 125I implant with an 85.9% 5-year PSA-RFS (p = n.s.). Analysis of Gleason score subgroups 2-4, 5-6, and 7-9 failed to show any significant difference in PSA-RFS comparing isotopes. Pretreatment PSA subgroups of < or = 10 or > 10 ng/ml also failed to show any significant difference in PSA-RFS survival comparing isotopes. Analysis of postimplant dosimetry using dose delivered to 90% of the prostate volume (D90) did not identify any difference between the isotope groups. CONCLUSIONS: This matched pair analysis failed to demonstrate a difference for 125I and 103Pd in PSA-RFS for patients undergoing TIPPB. In addition, there were no observed advantages for either 125I or 103Pd in either the low or high Gleason score groups. This data indicates that the role of isotope selection for patients undergoing TIPPB requires further clarification.     

Intraoperative optimized inverse planning for prostate brachytherapy: early experience.

PURPOSE: To demonstrate the feasibility of an intraoperative inverse planning technique with advanced optimization for prostate seed implantation. METHODS AND MATERIALS: We have implemented a method for optimized inverse planning of prostate seed implantation in the operating room (OR), based on the genetic algorithm (GA) driven Prostate Implant Planning Engine for Radiotherapy (PIPER). An integrated treatment planning system was deployed, which includes real-time ultrasound image acquisition, treatment volume segmentation, GA optimization, real-time decision making and sensitivity analysis, isodose and DVH evaluation, and virtual reality navigation and surgical guidance. Ten consecutive patients previously scheduled for implantation were included in the series. RESULTS: The feasibility of the technique was established by careful monitoring of each step in the OR and comparison with conventional preplanned implants. The median elapsed time for complete image capture, segmentation, GA optimization, and plan evaluation was 4, 10, 2.2, and 2 min, respectively. The dosimetric quality of the OR-based plan was shown to be equivalent to the corresponding preplan. CONCLUSION: An intraoperative optimized inverse planning technique was developed for prostate brachytherapy. The feasibility of the method was demonstrated through an early clinical experience.