The Value of PSA Measurements at 30 Gy, 50 Gy and 60 Gy for Dose Limitation in Patients with Radiotherapy for PSA Increase after Radical Prostatectomy

BACKGROUND: Radiation therapy is a treatment option for patients with rising PSA after radical prostatectomy without histological evidence of local relapse and no signs of distant metastases. Prior to radiotherapy there is no certainty whether a patient is going to respond to the treatment or not. When total doses of more than 60 Gy are given there is an exponential rise in treatment-related late toxicity. Therefore those patients in whom radiotherapy later appears to be ineffective may benefit from a dose restriction to 50-60 Gy. The aim of this study was to examine the prognostic value of PSA levels evaluated during radiotherapy. PATIENTS AND METHODS: 41 patients with rising PSA level following prostatectomy received radiotherapy to the prostatic bed and were treated up to a median dose of 66.6 Gy. We evaluated serum PSA levels during radiotherapy at 30 Gy, 50 Gy, and 60 Gy and compared them to the pre-radiotherapy PSA level and the outcome of radiotherapy. RESULTS: After radiotherapy, 31 patients (76%) had either undetectable (n = 15), or decreasing but still detectable PSA levels (n = 16) and ten patients (24%) had rising PSA levels and did not respond. PSA evaluation at 30 Gy showed that 26% (8/31) of those patients who would respond to radiotherapy still had a rising PSA when compared to pretreatment PSA. At 50 Gy and 60 Gy 93% (27/29) of these patients had decreasing PSA levels. In contrast, 75% (6/8) and 88% (7/8) of those patients in whom radiotherapy was not effective had rising PSA levels at 50 Gy and 60 Gy (p < 0.05). CONCLUSIONS: PSA measurements at 30 Gy, 50 Gy and 60 Gy for radiotherapy of PSA increase following radical prostatectomy without histologically proven local recurrence gives valuable information about the later tumor response. Therefore it possibly gives the opportunity to finish radiotherapy between 50 and 60 Gy, as almost all patients with continued PSA increase at 60 Gy do not stand to profit from radiotherapy. In these patients dose limitation would significantly decrease the risk of late side effects, especially for the bladder and the rectum. PSA evaluations at 30 Gy and 50 Gy or 60 Gy are recommendable.     

Potential of ultrasonography and ultrasonography-guided biopsy in the diagnosis of local recurrence following radical prostatectomy

INTRODUTION: We investigated the diagnostic role of combined transrectal US (TRUS) and biopsy to detect recurrent cancer after radical prostatectomy, in patients with negative bone scintigraphy and elevated prostate specific antigen (PSA) levels. MATERIALS AND METHODS: From March, 1997, to May, 1998, we examined 12 patients with persistently detectable serum PSA levels and negative bone scintigraphy. At the time of diagnosis, an average 36 months had elapsed since prostatectomy. Digital rectal examination (DRE) and disease stage at the time of surgery were also considered. Patients age ranged 47 to 83 years (mean: 65). All patients underwent TRUS with a 7.5 MHz biplane probe; biopsy was performed with a 16 G cutting needle. TRUS findings were considered suspicious if the scan showed any unusual hypoechoic tissue adjacent to the bladder neck, in retrotrigone or peri-retroanastomotic site. In these cases a transperineal US-guided biopsy was performed. RESULTS: The biopsy proved cancer in 10/12 cases (in 12 cases after two biopsies), showing a better diagnostic accuracy than DRE, which poorly distinguished postoperative changes from recurrent or residual cancer. CONCLUSIONS: The early detection of recurrences after radical prostatectomy in patients with negative bone scintigraphy is feasible when the above examinations are performed in the same order as described: PSA levels, if altered, indicate the patients to be submitted to TRUS. The latter may be falsely negative in some cases because small recurrences may exhibit no findings at US, and therefore US-guided biopsy of peri-retro-anastomotic regions should be always performed too. The recurrence must be confirmed at histology because histologic findings help choose adjuvant treatment and/or radical irradiation.     

Results of Three Dimensional Conformal Radiotherapy and Hormonal Therapy for Local Recurrence after Radical Prostatectomy

Background and Purpose: Analysis of treatment results of combined three–dimensional conformal radiotherapy (3DCRT) and hormonal therapy in patients with locally recurrent prostate cancer after radical prostatectomy.Patients and Methods: Between 1992 and 1998, 24 patients presented with a rising prostate–specific antigen (PSA) between 4 and 152 months following radical prostatectomy and a local recurrence demonstrated by imaging. Recurrence was biopsy–proven in 13 cases. All patients were treated with 3DCRT to a total dose of 60–70 Gy. 21 patients (88%) received adjuvant hormone therapy up to a maximum of 6 months.Results: All patients showed a response in PSA values after therapy. Median follow–up is 43 months. Overall survival is 80% and 67% at 3 and 5 years, respectively. Biochemical control rates are 53% and 38% at 3 and 5 years, respectively. 14 patients developed a second PSA relapse. Acute and late toxicities, classified with the RTOG score, were moderate.Conclusion: Radiotherapy and short–term adjuvant hormone therapy represent an effective and well–tolerated treatment for locally recurrent prostate cancer after radical prostatectomy resulting in good local control. Long–term prognosis in terms of biochemical control and disease–specific survival remains poor.     

Salvage low-dose-rate brachytherapy for local recurrences after prostatectomy and adjuvant or salvage external beam irradiation: Feasibility study on five patients and literature review

PurposeTo assess the feasibility and tumor outcome of re-irradiation with low-dose-rate brachytherapy for macroscopic local recurrences after radical prostatectomy (RP) followed by adjuvant or salvage external beam radiation therapy (EBRT).Methods and MaterialsBetween 2011 and 2018, five men with histologically proven local failure within the prostate (4) or seminal vesicle bed (1) after RP and adjuvant or salvage EBRT (median dose: 67.5 Gy) underwent a salvage brachytherapy (S-BT). The median delay after EBRT was 86 months (range 75–234). Two patients were castration-resistant at the time of S-BT. The gross tumor volume was defined on a multiparametric MRI and transrectal US imaging. Echo-guided transperineal implants of Iodine-125 seeds were optimized with a per-operative dosimetry and delivered with the seed-selectron.ResultsA high conformity was achieved with a high dose to the CTV (D_95% > 145 Gy in all but one) and very low dose to the rectum, urethra, and bladder. With a median followup of 21 months, all but one patient experienced nodes and/or bone metastases. Local control was achieved in 3/4 of evaluable patients (local failure distant to the treated volume in one). To date, no Grade 2 or more late toxicities were observed.ConclusionFor selected patients, focal local recurrence brachytherapy after PR and EBRT appears technically feasible and safe, but the efficacy remains uncertain as the majority of patients quickly relapsed at other sites. Large prospective studies are still required to better select patients who will benefit from this strategy.     

Outcomes of salvage high dose-rate brachytherapy with or without pelvic external beam radiotherapy in patients with palpable local recurrence of prostate cancer after radical prostatectomy

PurposeThis study aims to evaluate the outcomes and toxicities in patients with palpable local recurrence of prostate cancer after radical prostatectomy (RP), who were treated with salvage high dose-rate brachytherapy (HDR-BT) with or without pelvic external beam radiotherapy (EBRT).MethodsThis retrospective review included patients with palpable local recurrence of prostate cancer after RP who underwent salvage HDR-BT at a single institution between 2002 and 2020. HDR-BT regimens included 950 cGy x 2 (N = 4) or 1500 cGy x 1 (N = 2) combined with EBRT; or monotherapy with 950 cGy x 4 (N = 1) or 800 cGy x 2 (N = 1). Toxicity was graded according to CTCAE Version 5.0.ResultsA total of 8 patients were included. Median follow-up was 49 months (range: 9–223 months). Median age at time of salvage brachytherapy was 68 years (range: 59–85 years). Seven out of 8 patients were alive at last follow-up. There have been no locoregional recurrences. Three patients developed distant metastatic disease. One patient developed acute grade 3 urinary obstruction requiring catheterization, which lasted for 1 day postbrachytherapy. One patient developed late grade 3 urinary incontinence 18 months after brachytherapy. There were no other grade 2+ toxicities.ConclusionsThis study demonstrates the safety and efficacy of salvage HDR-BT in the setting of palpable local recurrence of prostate cancer after RP, with durable locoregional control and acceptable rates of toxicity. HDR-BT should be further explored as an option for dose-escalated salvage radiotherapy after prior radical prostatectomy.     

Postoperative radiotherapy after radical prostatectomy for prostate carcinoma: the experience of the Brescia Radium Institute

PURPOSE: The purpose of this study was to evaluate the efficacy of postoperative radiotherapy in reducing the incidence of prostate carcinoma (PCa) recurrences after radical prostatectomy (RP), define the importance of the time interval between surgery and radiotherapy for prognosis and the toxicity of the treatment in comparison with radiotherapy or surgery alone. MATERIALS AND METHODS: We examined 97 patients who consecutively underwent postoperative radiotherapy after RP between 1980 and 2003. The treatment was considered "adjuvant" if was conducted less than 6 months after RP, if there was no macroscopic residual disease and if there was no progressive increase in serum prostate-specific antigen (PSA) and "salvage" if performed more than 6 months after RP, for the presence of macroscopic recurrence or with rising PSA. Radiotherapy was salvage in 56 patients and adjuvant in 41. Age range was 60-70 years in 80% of patients, and the Karnofsky index was over 80 in 78% of cases. Histology revealed extracapsular spread in 60% of patients. Preradiotherapy PSA was higher than 1 ng/ml in 36%. Radiotherapy was performed on the surgical bed only in 80%, and the total dose was 70 Gy in 62% of cases. RESULTS: Recurrence-free survival (RFS) at 5 years and 10 years was 53+/-8% and 32+/-14.2%, respectively, for the whole sample; 76+/-9% and 38+/-2.7% for patients treated with adjuvant radiotherapy and 36+/-10% and 28+/-10% for those treated with salvage radiotherapy (p<0.01). Moreover, the 5-year RFS was better in the group treated with adjuvant radiotherapy and PSA less than or equal to 1 ng/ml (p<0.05). Treatment toxicity was acceptable. CONCLUSIONS: Postoperative radiotherapy improves RFS and reduces the risk of local recurrence. The best results are obtained with early postoperative treatment ("adjuvant"); adjuvant radiotherapy of high-risk forms yields better results if performed with PSA less than or equal to 1 ng/ml.     

Feasibility and Early Results of Interstitial Intensity-Modulated HDR/PDR Brachytherapy (IMBT) with/without Complementary External-Beam Radiotherapy and Extended Surgery in Recurrent Pelvic Colorectal Cancer

BACKGROUND: A new multimodality treatment concept consisting of extended resection and postoperative fractionated intensity-modulated interstitial brachytherapy (IMBT) was introduced for pelvic recurrence of colorectal carcinoma. PATIENTS AND METHODS: 46 patients received extended resection and single plastic tubes were sutured directly onto the tumor bed. IMBT was started within 2 weeks postoperatively with a median dose of 24.5 Gy (5-35 Gy). Patients were treated either with high-dose-rate brachytherapy (HDR; n = 23) or with pulsed-dose-rate brachytherapy (PDR; n = 23). 25 patients received complementary 45-Gy external-beam irradiation (EBRT) to the pelvic region after explanting the plastic tubes. RESULTS: Median follow-up was 20.6 months (7-107 months) and mean patient survival 25.7 +/- 25.8 months (median 17, range 1-107 months). After 5 years overall survival, disease-free survival and local control rate were 23%, 20% and 33%, significantly influenced by the resectional state. There was a trend in favor of PDR compared to HDR, which reached statistical significance in patients who had not received additional EBRT. CONCLUSION: The combination of extended surgery and postoperative interstitial IMBT is feasible and offers effective interdisciplinary treatment of recurrent colorectal cancer. In this small and inhomogeneous cohort of patients PDR seems to be more effective than HDR, particularly when application of complementary EBRT is not possible. None of the patients who required resection of distant metastasis survived > 2 years in this study.     

The potential value of power Doppler ultrasound imaging compared with grey-scale ultrasound findings in the diagnosis of local recurrence after radical prostatectomy

AIM: To determine the value of power Doppler ultrasound (PDUS) imaging during transrectal ultrasonography (TRUS) in detecting local recurrence after radical retropubic prostatectomy (RRP). MATERIALS AND METHODS: Eighteen patients were evaluated in whom local recurrence of prostate cancer was suspected on the basis of elevated serum prostate-specific antigen (PSA) levels (above 0.4 ng/ml) after RRP with no evidence of metastatic disease. Grey-scale TRUS and PDUS-guided biopsies of the vesicourethral anastomosis (VUA) and perianastomotic soft tissues were obtained after TRUS examinations of the prostatic fossa. The ability to detect locally recurrent prostate cancer using grey-scale TRUS alone was compared with TRUS combined with PDUS. RESULTS: Fifteen of the 18 patients (83%) had positive biopsies for local recurrent tumour at histological examination. TRUS alone detected grey-scale abnormalities in 15 of 18 patients (83%), of whom 14 (77%) had positive TRUS-guided biopsies. PDUS during TRUS showed hypervascularity in 14 of 18 patients (77%). Biopsies of these hypervascular regions were positive in all patients (100%). The sensitivity and specificity of TRUS alone in detecting recurrent tumour were 93 and 67%, respectively, with a positive predictive value (PPV) of 93% and a negative predictive value (NPV) of 67%. TRUS combined with PDUS had a sensitivity and specificity of 93 and 100%, respectively, with a PPV and a NPV of 100 and 75%, respectively.     

Hypofractionated Conformal HDR Brachytherapy in Hormone Naïve Men with Localized Prostate Cancer

PURPOSE: To analyze the long-term effect of local dose escalation using conformal hypofractionated high-dose-rate brachytherapy (HDR-BT) boost and pelvic external-beam radiation therapy (EBRT) in hormone-na?ve men with localized prostate cancer. PATIENTS AND METHODS: A total of 579 men were consecutively treated with pelvic EBRT and dose escalating HDR-BT since 1986 in two prospective trials: 378 patients at William Beaumont Hospital (1991-2002), and 201 patients at Kiel University (1986-1999). BT optimization was done modulating both, the dwell times and spatial source positions. A short course of neoadjuvant/concurrent androgen deprivation therapy was given to 222 patients. Hormone-na?ve patients only (n = 324) with a follow-up > or = 18 months were analyzed. All patients had at least one poor prognostic factor (stage > or = T2b, Gleason Score > or = 7, pretreatment prostate-specific antigen [PSA] > or = 10 ng/ml): any one factor 122 patients, any two factors 122 patients, and three factors 80 patients. This cohort was stratified by equivalent dose (ED): dose level 1, < or = 94 Gy, n = 58, and dose level 2, > 94 Gy, n = 266, assuming an alpha/beta ratio of 1.2. The ASTRO definition for biochemical failure was used. RESULTS: Mean follow-up was 5.3 years (1.5-13.9 years). For all 324 patients, the 5-year biochemical control (BC) rate was 79%. Cancer-specific survival was 98%, and overall survival 90%. Similar analysis by institution demonstrated no difference in outcomes. For the entire cohort of hormone-na?ve men, dose escalation to > 94 Gy resulted in a better 5-year BC of 59% versus 85% (p < 0.001). Discriminating by risk group a striking dose escalation effect was seen in the groups with two or three poor prognostic factors (p = 0.022 and < 0.001, respectively). In the group with only one poor prognostic factor, no statistical difference could be detected questioning the need for ED > 94 Gy. CONCLUSION: The results demonstrate that conformal HDR-BT is a successful method for delivering very high radiation dose to the prostate. The ability to escalate dose to ED > 94 Gy was reflected in improved long-term outcomes in terms of BC, significantly for those patients with two or three poor prognostic factors reaching BC rates of 85%.     

A prospective dose escalation trial of high-dose-rate brachytherapy boost for prostate cancer: Evidence of hypofractionation efficacy?

PURPOSE: The study aimed to evaluate mature outcomes of a Phase I/II high-dose-rate brachytherapy (HDRB) boost protocol. METHODS AND MATERIALS: We analyzed data from 88 patients with T1a-T3a, N0, M0 prostate adenocarcinoma treated on a prospective Phase I/II HDRB boost protocol of 16 (n = 47) or 20 Gy (n = 41) in four fractions, without planned androgen deprivation therapy. HDRB was added to 46 Gy of external beam radiotherapy (EBRT). Outcomes were compared to a contemporaneous retrospective cohort of 104 patients receiving 66 Gy EBRT monotherapy. The primary endpoint was freedom from biochemical failure, defined as a 2 ng/mL rise above the lowest prostate-specific antigen (PSA) (FFbFn2), whereas the American Society of Therapeutic Radiology and Oncology consensus definition (ACD) was used for comparative purposes. RESULTS: For the HDRB cohort, the overall actuarial 5-year FFbFn2 was 67.4% (95% CI: 58.2-75.5%). For the HDRB doses of 16 and 20 Gy, the 5-year FFbFn2 rates were 58.8% (95% CI: 41.9-72.5%) and 77.3% (95% CI: 64.4-88.3%), respectively (log-rank test p = 0.07). Compared to men treated with 66 Gy EBRT, using multivariate analysis, there was no significant benefit to using HDRB with the FFbFn2 outcome (p = 0.52), yet the ACD suggested a significant advantage (hazard ratio 0.50, 95% CI: 0.29-0.86, p = 0.011). There was a trend to better FFbFn2 outcomes with increasing biologically effective doses (p = 0.09), which was significant using the ACD (p = 0.0003). CONCLUSIONS: The data support HDRB boost as a potential means of dose escalation in prostate cancer. Significant findings using the ACD need to be validated with contemporary biochemical failure definitions. Prospective trials to optimize fractionation and evaluate outcomes in comparison to contemporary EBRT techniques are warranted.     

Strahlentherapie nach radikaler Prostatektomie

Background

Radiation therapy following radical prostatectomy in locally progressed prostate carcinoma has become increasingly important in the last few years as both adjuvant therapy in patients with pT3-tumors with or without positive margins and treatment for a PSA increase in local recurrence of disease. The background for this is the knowledge gained by using PSA that up to 60% of the patients with histopathologically confirmed pT3/4 tumors or involvement of the lymph nodes are systemically and/or locally progressive after 3 to 5 years if only surgical or radiation therapy was performed.

Results

A number of studies, albeit exclusively retrospective, substantiated a significantly high local tumor control by radiotherapy after radical prostatectomy. This holds true for adjuvant therapy with a PSA in the “zero range” as well as with a PSA increase from the “zero range”, whereby it must be taken into consideration that a certain percentage of treated patients with a PSA in the “zero-range” with or without positive margins actually do not need further therapy. Two retrospective studies demonstrated a significant better lengthening of “freedom from treatment failure” that is local and systemic progression of disease. Lengthening the survival time has, however, not yet been proven. With an increase in the PSA from the “zero range” after radical prostatectomy, there are indications that systemic metastatic spread already occurs with values higher than 2.5 to 4 ng/ml and the radiotherapy no longer has any curative intention.

conclusions

Adjuvant RT following radical prostatectomy gives better local control rates and probably better rates of “freedom from treatment failure” in patients with locally advanced prostate cancer with positive margins and probably in patients with negative margins. However, in retrospective studies no advantage in overall survival was shown.     

A comparison of early prostate-specific antigen decline between prostate brachytherapy and different fractionation of external beam radiation—Impact on biochemical failure

PurposeThe aim of this study was to compare early prostate-specific antigen (PSA) decline patterns and PSA nadirs between low-dose-rate seed prostate brachytherapy (LDR-PB) and different fractionations of external beam radiotherapy (EBRT) and their predictive importance for biochemical failure (bF).Methods and MaterialsPatients with D'Amico low- or intermediate-risk prostate cancer who underwent a single-modality treatment without androgen deprivation were included in this study. Three different treatment groups were compared: (1) normofractionation EBRT up to 70.2–79.2 Gy/1.8–2.0 Gy, (2) LDR-PB, and (3) EBRT with hypofractionation 60 Gy/3 Gy daily or 5–7.25 Gy once a week over 9–5 weeks, to a total dose of 45–36.25 Gy, respectively. The log-rank test, Cox regression analysis, and nonparametric tests were used.ResultsWe analyzed 892 patients: the median followup for patients without bF was 84 months (interquartile range 60–102 months), with 12% of patients experiencing bF. The PSA decline within the first 15 months was generally exponential. LDR-PB showed a faster early exponential decline compared with EBRT treatments, but whether decline was fast or slow had no influence on recurrence. The only factors that were positive predictive factors in univariate and multivariate analyses were the time to nadir >48 months (median), PSA nadir <0.5 ng/mL, and <0.2 ng/mL (all p < 0.001).ConclusionsAlthough there are significant differences in early exponential PSA decline between different treatments, only the PSA nadir and longer time to nadir were predictive factors for bF.     

Preliminary toxicity and prostate-specific antigen response of a Phase I/II trial of neoadjuvant hormonal therapy, 103Pd brachytherapy, and three-dimensional conformal external beam irradiation in the treatment of locally advanced prostate cancer

PURPOSE: Standard therapies for locally advanced prostate cancer have resulted in suboptimal disease control rates. A Phase I/II trial was designed for patients with positive seminal vesicle biopsies, prostate-specific antigen (PSA) >15 ng/ml, Gleason score > or =8 or clinical classification T2c-T3 to improve local control and to test the tolerance of the prostate to high-dose radiation by using neoadjuvant hormonal therapy, 103Pd brachytherapy, and conformal three-dimensional external beam radiation therapy (EBRT). This article outlines treatment-related morbidity and PSA response to this regimen and analyzes the effect of escalating doses of brachytherapy. METHODS AND MATERIALS: Forth-three patients with T1c-T3 prostate cancer were enrolled in a Phase I/II trial from March 1994 through September 1997. Follow-up ranged from 12 to 64 months (median, 32 months). Pretreatment PSA ranged from 2.1 to 202 ng/ml (median, 16 ng/ml). Seventy-seven percent (33 of 43) of patients had high-grade tumors (score > or =7). Seventy-four percent (32 of 43) had stage > or =T2c. A total of 21 (49%) patients had positive seminal vesicle biopsies. Treatment consisted of hormonal therapy for 3 months with leuprolide and flutamide followed by a 103Pd implant and, 2 months later, 59.4 Gy of three-dimensional EBRT. Hormonal therapy was continued for 9 months. The planned 103Pd dose was escalated from 57 Gy (13 patients) to 77 Gy (13 patients) to 86 Gy (17 patients). RESULTS: The actuarial freedom from PSA failure (PSA>0.5 ng/ml) at 4 years was 74%. There were no significant differences found when analyzing patients by presenting PSA or seminal vesicle status. There was a trend toward improved outcome with higher doses delivered to the prostate via the implant. Patients receiving doses > or =65 Gy (31 patients) had a freedom from PSA failure rate at 4 years of 89.5%, compared with 52.5% for those receiving doses <65 Gy (10 patients; p=0.08). The last PSA values for those patients free from PSA failure were < or =0.1 ng/ml in 25 (69%), >0.1-0.2 ng/ml in 5 (14%), and >0.2-0.5 ng/ml in 6 (17%). The actuarial freedom from developing Grade 2 proctitis was 75% at 4 years. There was a trend toward increased proctitis with increasing prostate implant doses. Patients with doses < or =70 Gy (n=12) had a 92% freedom from Grade 2 proctitis compared with 67.5% for those with doses delivered to 90% of the gland from a dose-volume histogram of >70 Gy (n=29) (p=0.15). There were no cases of Grade 3 or 4 proctitis. The 3-year actuarial preservation of sexual potency rate was 43%. CONCLUSIONS: The preliminary results from this regimen show an improvement in PSA control for this group of locally advanced prostate cancer patients over more standard therapies. To maximize control while minimizing toxicity, doses of 65-70 Gy of 103Pd should be used when 59.4 Gy of three-dimensional EBRT is delivered. Longer follow-up will be needed to further substantiate these findings.     

Variations in patterns of concurrent androgen deprivation therapy use based on dose escalation with external beam radiotherapy vs. brachytherapy boost for prostate cancer

PurposeRetrospective data suggest less benefit from androgen deprivation therapy (ADT) in the setting of dose-escalated definitive radiation for prostate cancer, especially when a combination of external beam radiotherapy (EBRT) and brachytherapy approaches are used. This study aimed to test the hypothesis that patients with prostate cancer with intermediate- or high-risk disease undergoing extreme dose escalation with a brachytherapy boost are less likely to receive ADT.Methods and MaterialsData from the National Cancer Database were extracted for men aged 40–90 years diagnosed with node-negative, non-metastatic prostate cancer from 2004 to 2015. Only patients with intermediate- or high-risk disease who were treated with definitive radiotherapy were included. The association and patterns of care between dose escalated radiotherapy and ADT receipt were assessed using multivariable logistic regression.ResultsPatients with unfavorable intermediate- and high-risk prostate cancer were significantly less likely to receive ADT if they underwent dose escalation with a combination of EBRT and brachytherapy (odds ratio 0.67, p < 0.0001). Over time, this decrease in ADT utilization has widened for patients with unfavorable intermediate-risk disease. There was no difference in ADT utilization when comparing patients treated with non–dose-escalated EBRT to those treated with dose-escalated EBRT (without brachytherapy).ConclusionIn this large national database, patients with unfavorable intermediate- and high-risk prostate cancer were significantly less likely to receive guideline-indicated ADT if they underwent extreme dose escalation with combined radiation modalities. As we await prospective data guiding the utility of ADT with dose escalated radiation, these findings suggest potential underutilization of ADT in patients at higher risk of advanced disease.     

Radiotherapy of local recurrence of rectal carcinoma

In retrospective, non-randomized study were analyzed 45 patients with local recurrences of rectal carcinoma treated by combined external beam radiotherapy (EBRT) and "High dose rate (HDR) remote afterloading" brachytherapy in the period from January 1st, 1988 to May 1st, 1988. Depending on the localization of the local recurrent disease, 20 patients were with vaginal relapse, 13 with vaginal and presacral, 9 with perineal and 3 with presacral and rectal. Combined radiotherapy was applied as follows: 33 patients (73.3%) had EBRT with endovaginal brachytherapy, 3 (6.7%) EBRT plus intraluminal brachytherapy and 9 (20%) patients EBRT plus interstitial brachytherapy. Techniques with 3 and 4 field for EBRT were used and doses ranged 45-65 Gy with convenient fractionation were applied, combined with the doses ranged 15-35 Gy for brachytherapy. Radiotherapy was planned according to the computer tomography cross image on simulator with computer planning. Complete regression of the tumor was observed in 19 patients (42.2%), and partial in 23 patients (51.1%). Median follow-up period was 34 months (8-72). Acute radiation adverse effects were registered in 32 patients, and late sequels in 6 (13.3%). Overall 3-year survival rate was 54% and disease-free survival rate was 34% in the same period.     

Outcome of post-prostatectomy radiotherapy in one institution

We present a retrospective study to evaluate the outcome of postoperative radiotherapy for biochemical or clinical recurrent prostate cancer. Twenty-six patients (median age 60 years) underwent radiotherapy after radical prostatectomy between January 1997 and January 2004. Seven patients received adjuvant radiotherapy and 19 received salvage radiotherapy. The median prostate-specific antigen at diagnosis was 8.6 (0.9-89) and most (23 patients) presented with T(3)N(0) disease. The median follow up was 19.5 months (5-84 months). All patients received a dose of 61.2 Gy at 1.8 Gy per fraction, 20 initially receiving 45 Gy to the lesser pelvis. The median dose to the bladder, rectum and left femoral head were 55.6, 57.5 and 33.8 Gy, respectively. All patients were managed radiotherapeutically by the first author. Twenty-four patients are alive. Two patients have died, one from oesophageal cancer and the second from metastatic prostate cancer. Two other patients also developed metastatic disease. Four asymptomatic patients with a rising prostate-specific antigen are under observation. None of the 26 patients has developed a local recurrence. Seven patients have developed grade 1 late bowel effects and three a grade 2 late effect. Eight patients suffer from grade 1 late genitourinary effects and two from grade 2 effects. One patient developed impotence, whereas 23 patients were rendered impotent postoperatively. There were no grade 3/4 late effects. Postoperative radiotherapy is well tolerated and provides effective local control.     

Health-Related Quality of Life Measurement in Long-Term Survivors and Outcome Following Radical Radiotherapy for Localized Prostate Cancer

PURPOSE: To report long-term outcomes in terms of health-related quality of life (HRQoL) and survival of a dose-escalating radiotherapy protocol and to validate a new disease-specific HRQoL instrument. PATIENTS AND METHODS: 189 consecutive men with prostate cancer were analyzed; 127 patients had T1-2 (1% T1, 66% T2) and 62 patients (33%) T3 tumors. The pelvic lymphatics were treated to a dose of 50 Gy by external-beam irradiation. The prostate dose was limited to 40 Gy using compensators. The prostate was treated to the total nominal dose of 70 Gy using high-dose-rate (HDR) brachytherapy. The fraction dose was 15 Gy in the McNeal zone (planning target volume [PTV] 1), while 8-9 Gy were applied in the entire prostate (PTV 2). The HRQoL of the 145 long-term survivors was assessed using the EORTC QLQ-C30 and a new prostate-specific instrument (PSM-G 1.0). The reliability of the instruments used and HRQoL scale scores were calculated. Uni-/multivariate analyses of variance were performed. RESULTS: At a mean follow-up of 6.5 years 86.3% of the patients were disease-free, and 78% were biochemically controlled. The mean Cronbach's alpha-values were 0.81 for the QLQ-C30, and 0.74 for the prostate-specific module. Univariate analyses of variance by T-stage, grading, prostata-specific antigen (PSA) status after therapy and adjuvant androgen suppression (AS) revealed that PSA elevation after irradiation and AS were associated with significantly diminished HRQoL. In multivariate analyses AS significantly lowered the HRQoL without survival benefit. CONCLUSION: The described radiotherapy regimen represents a curative and well-tolerated treatment for localized prostate cancer. The HRQoL assessment with both instruments used was reliable. Adjuvant AS and PSA elevation were associated with diminished HRQoL.     

Endobronchial brachytherapy and optimization of local disease control in medically inoperable non-small cell lung carcinoma: a matched-pair analysis

PURPOSE: External beam radiation therapy (EBRT) alone for early stage, medically inoperable non-small cell lung cancer (MILC) can produce local disease control and sometimes cure. We have previously reported that higher EBRT doses result in improved disease control and, for patients with tumors > or =3.0 cm, improved survival. This report describes the impact of dose escalation with endobronchial brachytherapy boost during or following EBRT upon local disease control. METHODS AND MATERIALS: Medical records of 404 patients with MILC treated with radiotherapy alone were reviewed. Thirty-nine patients received a planned endobronchial brachytherapy boost during or following a course of EBRT. A matched-pair analysis of disease control and survival was performed by matching each brachytherapy patient to 2 EBRT patients from a reference group of the remaining patients. RESULTS: Endobronchial brachytherapy boost significantly improved local disease control over EBRT alone (58% vs. 32% at 5 years). The local control benefit for brachytherapy was found to be limited to patients with T(1-2) disease or tumors < or =5.0 cm. Among these patients treated with endobronchial boost, EBRT doses of > or =6500 cGy were necessary to optimize local disease control. No overall survival differences were observed at 3 years. Excess toxicity with brachytherapy was not observed. CONCLUSION: Endobronchial brachytherapy boost enhances local disease control rates in MILC treated with EBRT. Local control outcome is optimized when radical EBRT doses are used in conjunction with brachytherapy.