Monotherapy For Prostate Cancer Research Articles

Five-Year Biochemical Outcome in Patients Treated with 131Cs Brachytherapy as Monotherapy for Prostate Cancer

Five-Year Biochemical Outcome in Patients Treated with 131Cs Brachytherapy as Monotherapy for Prostate Cancer

Biochemical Recurrence After Robot-assisted Radical Prostatectomy in a European Single-centre Cohort with a Minimum Follow-up Time of 5 Years

BackgroundRobot-assisted radical prostatectomy (RARP) is an increasingly commonly used surgical treatment option for prostate cancer (PCa); however, its longer-term oncologic results remain uncertain. ObjectiveTo report biochemical recurrence–free survival (BRFS) outcomes for men who underwent RARP ≥5 yr ago at a single European centre. Design, setting, and participantsA total of 944 patients underwent RARP as monotherapy for PCa from January 2002 to December 2006 at Karolinska University Hospital, Stockholm, Sweden. Standard clinicopathologic variables were recorded and entered into a secure, ethics-approved database made up of those men with registered domiciles in Stockholm. The median follow-up time was 6.3 yr (interquartile range: 5.6–7.2). Outcome measurements and statistical analysisThe outcome of this study was biochemical recurrence (BCR), defined as a confirmed prostate-specific antigen (PSA) of ≥0.2 ng/ml. Kaplan-Meier survival plots with log-rank tests, as well as Cox univariable and multivariable regression analyses, were used to determine BRFS estimates and determine predictors of PSA relapse, respectively. Results and limitationsThe BRFS for the entire cohort at median follow-up was 84.8% (95% confidence interval [CI], 82.2–87.1); estimates at 5, 7, and 9 yr were 87.1% (95% CI, 84.8–89.2), 84.5% (95% CI, 81.8–86.8), and 82.6% (95% CI, 79.0–85.6), respectively. Nine and 19 patients died of PCa and other causes, respectively, giving end–of–follow-up Kaplan-Meier survival estimates of 98.0% (95% CI, 95.5–99.1) and 94.1% (95% CI, 90.4–96.4), respectively. Preoperative PSA >10, postoperative Gleason sum ≥4 + 3, pathologic T3 disease, positive surgical margin status, and lower surgeon volume were associated with increased risk of BCR on multivariable analysis. This study is limited by a lack of nodal status and tumour volume, which may have confounded our findings. ConclusionsThis case series from a single, high-volume, European centre demonstrates that RARP has satisfactory medium-term BRFS. Further follow-up is necessary to determine how this finding will translate into cancer-specific and overall survival outcomes.

An age-corrected matched-pair study of erectile function in patients treated with adaptive intensity modulated radiation therapy (IMRT) versus high-dose-rate brachytherapy (HDR) in prostate cancer.

225 Background: Increasing age is a likely contributor to erectile dysfunction (ED) after radiotherapy for prostate cancer. A matched-pair (MP) analysis, with age as a criterion, was used to investigate ED after IMRT and HDR monotherapy for prostate cancer. Methods: 430 patients with low (63%) or intermediate risk (37%) prostate cancer with full or partial erectile function were treated between 4/00 and 9/10 with IMRT (n=215) or brachytherapy (n=215). Patients with follow up (FU) <1y were excluded. IMRT dose was 70.2–82.8 Gy (median 75.6) in 1.8 Gy/fx. HDR was given as 9.5 Gy x 4 (median), 13.5 Gy x 2 or 12 Gy x 2. MP, univariate, and multivariate analyses examined ED using CTCAEv4. Match criteria were age (±5y), Gleason (6,7), T stage (T1, T2), and PSA (<4, 4–10, >10). BF was by modified Phoenix criteria (nadir+5 for 2y, nadir+2 after). Results: Median FU was 3.4y (range 1–7.1) for IMRT and 3.1y (range 1–10.9) for HDR. There was no difference in PSA (4.8 vs. 4.6, p=0.4), T stage (88% vs. 88% T1, p=1.0) and Gleason score (63% vs. 63% 6, p=1.0) between IMRT and HDR. Despite age matching, IMRT patients were older (median 65 vs. 62 y, p=0.05). Pre-treatment potency grade 0, 1, and 2 were found in 70%, 14% and 15% of IMRT and 69%, 20% and 11% of HDR patients. 5y OS, CSS, and BF were 100%, 100% and 2.4% for IMRT, and 99% (p=0.35), 100% (p=1.0), and 10.6% (p=0.001) for HDR. On subset analysis of pre-treatment grade 0 patients, univariate analysis showed HDR (p<0.001), increasing Gleason (p=0.05) and increasing FU time (p<0.001) correlated with post-treatment ED, while age (p=0.32), PSA (p=0.46) and T stage (p=0.76) did not. On multivariate analysis, increasing FU time correlated with ED (p<0.001), while treatment type (p=0.10) and Gleason (p=0.49) did not. Conclusions: Both IMRT and HDR yield comparable low (25%) rates of 1+ ED for patients with no ED at baseline. Increasing age does not appear to significantly impact ED for both IMRT and HDR. [Table: see text]

PSA Bounce after HDR Monotherapy for Prostate Cancer: Magnitude, Kinetics and Clinical Correlates

PSA Bounce after HDR Monotherapy for Prostate Cancer: Magnitude, Kinetics and Clinical Correlates

Long-term QOL outcome after proton beam monotherapy for localized prostate cancer.

68 Background: High-dose conformal proton radiation for localized prostate cancer results in favorable clinical outcomes and low toxicity rates. Here, we report long-term quality of life (QOL) outcome for men treated with conformal protons. Methods: Serial QOL questionnaires were administered to men who received proton radiation. Long-term questionnaires (minimum 2 years) were completed by 72 patients. Men were stratified into functional groups from their baseline questionnaires (normal, intermediate or poor function) for each symptom domain. Symptom scores were calculated at baseline and long-term follow-up and expressed as mean values. QOL changes were assessed overall and within functional groups in a paired fashion using the Student's t-test. Results: The median age at treatment and follow-up were 66 years and 44 months, respectively. The median dose was 82 GyE (range 74-82 GyE). For all 72 patients, there were increased scores for incontinence (ID) (3.2 baseline vs. 9.9 long-term, p=<0.001), obstructive/irritative voiding (OID; 20 vs. 24, p=0.028), bowel (BD; 4.4 vs. 8.0, p=0.001) and sexual dysfunction (SD; 25 vs. 48, p<0.001). When stratified by functional category, more specific estimates were possible. For ID, only normal function was associated with a significant increased score (0 vs. 8.4 at baseline and long-term, p=<0.001); for OID, only the group with normal baseline function showed a significant increased score (12 vs. 17, p=0.01); similarly for BD, only men with normal function had a significant increased score (0 vs. 5.4, p<0.001). For SD, the score increased in men with normal (1.4 vs. 30, p<0.001) and intermediate function (17 vs. 46, p<0.001). Conclusions: Patient reported outcomes are sensitive indicators of treatment related sequelae and here quantitate, for the first time, the long-term consequences of proton monotherapy for prostate cancer. Analysis by baseline functional category is a useful means of predicting long-term QOL scores for an individual patient. High-dose proton radiation was associated with small increases in bowel dysfunction, obstructive/irritative voiding dysfunction and incontinence. With long term follow-up, sexual dysfunction increased more than any other symptom domain. No significant financial relationships to disclose.

Predictors in the outcome of 125I brachytherapy as monotherapy for prostate cancer

A number of different prostate cancer treatment modalities exist. Nomograms are used to assist clinicians and patients in choosing the most appropriate treatment. However, the predicted outcome for 125I brachytherapy is much worse than what would be expected considering the actual survival rates. This underestimation may result in suboptimal treatment decisions. Therefore, better predictors for outcome after 125I brachytherapy are necessary. The following factors, which may either influence outcome or predict outcome after brachytherapy, are discussed: tumor characteristics and risk stratification, patient age at treatment, obesity, adjuvant androgen-deprivation therapy, prostate-specific antigen bounce, implantation technique and dosimetry. For the prediction of outcome after 125I brachytherapy, as long as the quality of the implant is optimal, only high-risk prostate cancer was found to have a negative impact on outcome.

Monotherapeutic High-Dose-Rate Brachytherapy for Prostate Cancer: Five-Year Results of an Extreme Hypofractionation Regimen With 54 Gy in Nine Fractions

To evaluate an extreme hypofractionation regimen with 54 Gy in nine fractions provided by high-dose-rate (HDR) brachytherapy as monotherapy for prostate cancer by reporting 5-year clinical results. Between 1996 and 2005, 112 patients with localized prostate cancer were treated with HDR brachytherapy without external beam radiotherapy. Of the 112 patients, 15 were considered low risk, 29 intermediate risk, and 68 as high risk. The prescribed dose was uniformly 54 Gy in nine fractions within 5 days. Of the 112 patients, 94 also received hormonal therapy. The median follow-up time was 5.4 years. All the patients safely completed the treatment regimen. The 5-year prostate-specific antigen (PSA) failure-free, local control, disease-free survival, and overall survival rate was 83%, 97%, 87%, and 96%, respectively. The 5-year PSA failure-free rate for low-, intermediate-, and high-risk patients was 85% (95% confidence interval, 66-100%), 93% (95% confidence interval, 83-100%), and 79% (95% confidence interval, 69-89%), respectively. The significant prognostic factors for PSA failure were the initial PSA level (p = .029) and younger age (p = .019). The maximal toxicities observed were Grade 3 using the Common Terminology Criteria for Adverse Events, version 3.0, for both acute and late toxicity (6 and 3 patients had acute and late Grade 3 toxicity, respectively). Late Grade 2 toxicity was observed in 13 patients. Monotherapeutic HDR brachytherapy with an extreme hypofractionation regimen of 54 Gy in nine fractions associated with hormonal therapy was feasible, and its toxicity was acceptable. The interim tumor control rate at a median 5.4 years was promising, even for patients with locally advanced disease. This dose-fractionation scheme might be referred to by other terms, such as stereotactic body radiotherapy. Studies with longer follow-up periods and from multiple institutions are needed to confirm the efficacy of this novel approach.

Abstract 956: Targeting prostate cancer chemoprevention via the androgen receptor in a preclinical mouse model

Abstract Prostate cancer is strongly associated with increasing age, with about 96 % of the cases occurring in men over 60 years of age. The high incidence and late age of onset make prostate cancer an ideal target for chemoprevention strategies as even a modest delay in carcinogenesis would significantly reduce the incidence of the disease. Chlormadinone acetate (CA) is one of the steroidal anti-androgen agents used in combined androgen blockade therapy as well as monotherapy for prostate cancer in Japan. However, no reports have been published for the chemopreventive potential of CA. We evaluated the efficacy of low-dose administration of CA to prevent or suppress prostate cancer using our PTEN conditional gene targeting mouse model. Six-week-old mice were injected subcutaneously with CA (50 mg/kg 3X/week) until the age of 15 or 20 weeks. The genitourinary tracts (GUTs), consisting of the prostate, urethra, bladder, seminal vesicles and coagulating gland, were collected, weighed, fixed in formalin and imaged. GUT weights were significantly lower in CA-treated mice compared to untreated controls in a time dependent manner (P<0.01). Morphometric image analysis performed on the GUT to measure the prostate area revealed significant shrinkage of the prostate gland in CA-treated mice vs. the corresponding controls (P<0.001). Histopathological distribution analysis of normal, prostatic intraepithelial neoplasia (PIN) and tumor glands showed a decrease in the PIN but not normal or cancer glands in 15-week-old CA-treated mice compared to controls. However, similar analysis showed a dramatic decrease of cancer gland shrinkage in 20-week-old CA-treated mice with only marginal decreases of PIN compared to untreated controls. Immunohistochemical analysis of androgen receptor (AR) expression showed a significant decrease in nuclear localization and intensity CA-treated mice (P<0.001). Proliferation analysis of tumors by PCNA immunostaining showed a 30% reduction in 20-week-old mice treated with CA compared to untreated control mice (P<0.001). The apoptotic index in tumors if mice treated with CA increased three-fold to 3.16% compared to 1.12% on the corresponding control mice (P<0.004). Our data suggests that chemopreventive treatment with CA does not prevent the incidence of prostate cancer, however, it does inhibit the growth and progression of prostate cancer. Our findings may reveal a promising prophylactic strategy for the chemopreventive treatment of prostate cancer in high-risk individuals. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 956.

Use of Gold Markers for Setup in Image-Guided Fractionated High-Dose-Rate Brachytherapy as a Monotherapy for Prostate Cancer

In order to use a single implant with one treatment plan in fractionated high-dose-rate brachytherapy (HDR-B), applicator position shifts must be corrected prior to each fraction. The authors investigated the use of gold markers for X-ray-based setup and position control between the single fractions. Caudad-cephalad movement of the applicators prior to each HDR-B fraction was determined on radiographs using two to three gold markers, which had been inserted into the prostate as intraprostatic reference, and one to two radiopaque-labeled reference applicators. 35 prostate cancer patients, treated by HDR-B as a monotherapy between 10/2003 and 06/2006 with four fractions of 9.5 Gy each, were analyzed. Toxicity was scored according to the CTCAE Score, version 3.0. Median follow-up was 3 years. The mean change of applicators positions compared to baseline varied substantially between HDR-B fractions, being 1.4 mm before fraction 1 (range, -4 to 2 mm), -13.1 mm before fraction 2 (range, -36 to 0 mm), -4.1 mm before fraction 3 (range, -21 to 9 mm), and -2.6 mm at fraction 4 (range, -16 to 9 mm). The original position of the applicators could be readjusted easily prior to each fraction in every patient. In 18 patients (51%), the applicators were at least once readjusted > 10 mm, however, acute or late grade > or = 2 genitourinary toxicity was not increased (p = 1.0) in these patients. Caudad position shifts up to 36 mm were observed. Gold markers represent a valuable tool to ensure setup accuracy and precise dose delivery in fractionated HDR-B monotherapy of prostate cancer.

37 oral: Hdr Monotherapy for Prostate Cancer: A Simulation Study to Determine the Effect of Catheter Movement on Target Coverage and Normal Tissue Irradiation

37 oral: Hdr Monotherapy for Prostate Cancer: A Simulation Study to Determine the Effect of Catheter Movement on Target Coverage and Normal Tissue Irradiation

Correlation Between Dosimetric Parameters and Late Rectal and Urinary Toxicities in Patients Treated With High-Dose-Rate Brachytherapy Used as Monotherapy for Prostate Cancer

To evaluate the correlation between dosimetric parameters and late rectal and urinary toxicities in high-dose-rate brachytherapy (HDR-BT) used as monotherapy for prostate cancer. The data of 83 patients treated with HDR-BT alone for prostate cancer from 2001 through 2005 at Osaka University Hospital were analyzed. Median follow-up time was 36 months (range, 18-70). The total prescribed dose was 54 Gy in nine fractions over 5 days. Correlation between dosimetric parameters and late toxicities was examined. The means of V30, V40, V50, V60, V70, D1cc, D2cc, D5cc, and D10cc of the rectum were significantly higher in 18 patients who presented with late rectal toxicity (Grades 1-3 rectal bleeding) than in the other 65 patients who did not. A significant difference was observed for D1cc-10cc but not for D5-90. The statistically most significant difference was observed for V40 and D5cc. Late rectal toxicity rate was significantly higher for patients with rectal V40 >or= 8 cc than those with the rectal V40 < 8 cc (42% vs. 8%; p < 0.001), as well as for patients with rectal D5cc >or= 27 Gy compared with those with rectal D5cc < 27 Gy (50% vs. 11%; p < 0.001). Dosimetric parameters of the urethra of 15 patients with late urinary toxicity were not significantly different from the 68 patients without toxicity. Rectal V40 < 8 cc and D5cc < 27 Gy may be dose-volume constraints in HDR-BT used as monotherapy for prostate cancer.

Exercise therapy across the prostate cancer continuum

Exercise has been increasingly investigated as an adjunct therapy for cancer patients. The purpose of this paper is to comprehensively review the literature regarding exercise as a therapeutic adjunct for prostate cancer (PC). Several studies in patients with PC have shown quality of life improvements associated with exercise. Although no study has established the effect of exercise as a monotherapy for PC, the molecular mechanisms responsible for the potential association between exercise and PC are being elucidated. Given the low-risk, high-reward nature of these studies, further investigations are needed to better define the function of exercise along the PC continuum.

Neuroendocrine transdifferentiation induced by VPA is mediated by PPARγ activation and confers resistance to antiblastic therapy in prostate carcinoma

Prostate cancer (PCa) is the most commonly diagnosed cancer in men in the Western Countries. When prostatectomy fails to eradicate the primary tumor, PCa is generally refractory to all therapeutic approaches. Valproic acid (VPA) is a promising anticancer agent recently assigned to the class of histone deacetylase (HDAC) inhibitors. However molecular mechanisms underlying VPA action in PCa cells are largely unknown and further experimental validation to prove its potential application in clinic practice is needed. In our study we show that VPA is a potent inducer of neuro-endocrine transdifferentiation (NET) in androgen receptor null PCa cells, both in vitro and in vivo. NET was an early event detectable through the expression of neuro-endocrine (NE) markers within 72 hr after VPA treatment and it was associated to a reduction in the overall cell proliferation. When we interrupted VPA treatment we observed the recovery in residual cells of the basal proliferation rate both in vitro and in a xenograft model. The NET process was related to Bcl-2 over-expression in non-NE PCa cells and to the activation of PPARgamma in NE cells. The use of specific PPARgamma antagonist was able to reduce significantly the expression of NE markers induced by VPA. Our data indicate that the use of VPA as monotherapy in PCa has to be considered with extreme caution, since it may induce an unfavorable NET. In order to counteract the VPA-induced NET, the inhibition of PPARgamma may represent a suitable adjuvant treatment strategy and awaits further experimental validation.

On the use of Kodak CR film for quality assurance of needle loading in I-125 seed prostate brachytherapy

Low dose rate brachytherapy using implanted I-125 seeds as a monotherapy for prostate cancer is now in use in many hospitals. In contrast to fractionated brachytherapy treatments, where the effect of incorrect positioning of the source in one treatment fraction can be diminished by correcting the position in subsequent fractions, the I-125 seed implant is permanent, making correct positioning of the seeds in the prostate essential. The seeds are inserted into the prostate using needles. Correct configuration of seeds in the needles is essential in order to deliver the planned treatment. A comparison of an autoradiograph obtained by exposing film to the seed-loaded needles with the patient treatment plan is a valuable quality assurance tool. However, the time required to sufficiently expose Kodak XOMAT V film, currently used in this department is significant. This technical note presents the use of Kodak CR film for acquisition of the radiograph. The digital radiograph can be acquired significantly faster, has superior signal-to-noise ratio and contrast and has the usual benefits of digital film, e.g. a processing time which is shorter than that required for non-digital film, the possibility of image manipulation, possibility of paper printing and electronic storage.

Changes of Dose Delivery Distribution within the First Month after Permanent Interstitial Brachytherapy for Prostate Cancer

To evaluate changes of dose distribution for both the prostate and the surrounding tissues after permanent brachytherapy as monotherapy for prostate cancer. In 35 patients, CT scans were performed before, 1 day after (day 1) and 1 month after the implantation (day 30). Changes of prostate volume, dosimetric parameters, and distances between posterior prostate contour and rectal wall as well as prostate contour and prescription isodose were analyzed. Prostate volume increased from 37+/-11 cm3 (mean+/-standard deviation) to 49+/-12 cm3 on day 1 and dropped to 40+/-9 cm3 on day 30. Prostate V100 increased from 87+/-7% to 90+/-7%, prostate D90 from 138+/-21 Gy to 151+/-30 Gy. Mean rectal volume covered by the prescription isodose rose from 0.4 cm3 to 1.0 cm3; a changing distance between the prostate and rectal wall was excluded as a reason. Prostate D90 (day 1) and rectum V100 (day 30) proved to be significantly higher for larger prostate sizes. The distance between the prescription isodose and the prostate contour increased particularly at the posterior and inferior borders: 1.9 mm and 2.5 mm on average (0.1 mm and -0.7 mm at opposite borders, respectively). With a decreasing edema of the prostate, an increasing dose both to the prostate and the anterior rectal wall resulted--the postimplant interval is essential for the dosimetry report. Due to a larger edema, a higher prescription dose might be needed for optimal cancer control in smaller prostates. Compared to day 1, the dose to the surrounding tissues increased on day 30, particularly at the posterior and inferior prostate borders.

846 POSTER High-dose-rate brachytherapy as monotherapy for prostate cancer: Osaka University experience

846 POSTER High-dose-rate brachytherapy as monotherapy for prostate cancer: Osaka University experience

839 POSTER The impact of fractionation on acute toxicity in radical radiotherapy for bladder cancer

To evaluate the correlation between dosimetric parameters and late rectal and urinary toxicities in high-dose-rate brachytherapy (HDR-BT) used as monotherapy for prostate cancer.The data of 83 patients treated with HDR-BT alone for prostate cancer from 2001 through 2005 at Osaka University Hospital were analyzed. Median follow-up time was 36 months (range, 18–70). The total prescribed dose was 54 Gy in nine fractions over 5 days. Correlation between dosimetric parameters and late toxicities was examined.The means of V30, V40, V50, V60, V70, D1cc, D2cc, D5cc, and D10cc of the rectum were significantly higher in 18 patients who presented with late rectal toxicity (Grades 1–3 rectal bleeding) than in the other 65 patients who did not. A significant difference was observed for D1cc–10cc but not for D5–90. The statistically most significant difference was observed for V40 and D5cc. Late rectal toxicity rate was significantly higher for patients with rectal V40 ≥ 8 cc than those with the rectal V40 < 8 cc (42% vs. 8%; p < 0.001), as well as for patients with rectal D5cc ≥ 27 Gy compared with those with rectal D5cc < 27 Gy (50% vs. 11%; p < 0.001). Dosimetric parameters of the urethra of 15 patients with late urinary toxicity were not significantly different from the 68 patients without toxicity.Rectal V40 < 8 cc and D5cc < 27 Gy may be dose–volume constraints in HDR-BT used as monotherapy for prostate cancer.

HDR vs. LDR (Pd103 permanent implants) brachytherapy as monotherapy for prostate cancer. timing to onset and predictors of erectile dysfunction

HDR vs. LDR (Pd103 permanent implants) brachytherapy as monotherapy for prostate cancer. timing to onset and predictors of erectile dysfunction

HDR vs. LDR (Pd103 permanent implants) brachytherapy as monotherapy for prostate cancer. timing to onset and predictors of erectile dysfunction

Erectile dysfunction (ED) is the most frequent late toxicity after brachytherapy in patients (pts) with prostate cancer. We attempted to correlate the rate and timing to onset of ED after HDR brachytherapy and LDR permanent implants with Pd 103, with clinical and treatment-related factors.

241 poster Quality assurance for fractionated high dose rate afterloading brachytherapy as monotherapy for prostate cancer

241 poster Quality assurance for fractionated high dose rate afterloading brachytherapy as monotherapy for prostate cancer