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Research Interests: Cancer, Prostate Cancer, Medicine, Humans, Male, and 3 moreCryosurgery, Cryoablation, and Prostatic neoplasms
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The use of hormonal therapy with radiotherapy for prostate cancer: analysis of prospective randomised trials
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Anaplastic thyroid carcinoma (ATC) is a rare, aggressive malignancy, which is known to metastasize to the heart. We report a case of a patient with ATC with metastatic involvement of the pacemaker leads within the right atrium and right... more
Anaplastic thyroid carcinoma (ATC) is a rare, aggressive malignancy, which is known to metastasize to the heart. We report a case of a patient with ATC with metastatic involvement of the pacemaker leads within the right atrium and right ventricle. The patient survived external beam radiation treatment to his heart, with a radiographic response to treatment. Cardiac metastases are usually reported on autopsy; to our knowledge, this is the first report of the successful treatment of cardiac metastases encasing the leads of a pacemaker, and of cardiac metastases from ATCs, with a review of the pertinent literature.
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The NRG/RTOG 9413 study showed that whole pelvic radiotherapy (WPRT) plus neoadjuvant hormonal therapy (NHT) improved progression-free survival in patients with intermediate-risk or high-risk localised prostate cancer compared with... more
The NRG/RTOG 9413 study showed that whole pelvic radiotherapy (WPRT) plus neoadjuvant hormonal therapy (NHT) improved progression-free survival in patients with intermediate-risk or high-risk localised prostate cancer compared with prostate only radiotherapy (PORT) plus NHT, WPRT plus adjuvant hormonal therapy (AHT), and PORT plus AHT. We provide a long-term update after no years of follow-up of the primary endpoint (progression-free survival) and report on the late toxicities of treatment. The trial was designed as a 2 × 2 factorial study with hormonal sequencing as one stratification factor and radiation field as the other factor and tested whether NHT improved progression-free survival versus AHT, and NHT plus WPRT versus NHT plus PORT. Eligible patients had histologically confirmed, clinically localised adenocarcinoma of the prostate, an estimated risk of lymph node involvement of more than 15% and a Karnofsky performance status of more than 70, with no age limitations. Patients...
Research Interests: Oncology, Radiation, Radiation Therapy, Prostate Cancer, Medicine, and 15 moreCanada, Humans, Internal Medicine, Male, Lancet Oncology, Chemoradiotherapy, Prostate Specific Antigen, Adenocarcinoma, Leuprolide, Progression Free Survival, Neoplasm grading, Neoplasm staging, Prostatic neoplasms, Flutamide, and goserelin
A meta-analysis of sociodemographic variables and their association with late (>180 days from start of radiation therapy[RT]) bowel, bladder, and clustered bowel and bladder toxicities was conducted in patients with high-risk (clinical... more
A meta-analysis of sociodemographic variables and their association with late (>180 days from start of radiation therapy[RT]) bowel, bladder, and clustered bowel and bladder toxicities was conducted in patients with high-risk (clinical stages T2c-T4b or Gleason score 8-10 or prostate-specific antigen level >20) prostate cancer. Three NRG trials (RTOG 9202, RTOG 9413, and RTOG 9406) that accrued from 1992 to 2000 were used. Late toxicities were measured with the Radiation Therapy Oncology Group Late Radiation Morbidity Scale. After controlling for study, age, Karnofsky Performance Status, and year of accrual, sociodemographic variables were added to the model for each outcome variable of interest in a stepwise fashion using the Fine-Gray regression models with an entry criterion of 0.05. A total of 2432 patients were analyzed of whom most were Caucasian (76%), had a KPS score of 90 to 100 (92%), and received whole-pelvic RT+HT (67%). Of these patients, 13 % and 16% experienced ...
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There is considerable interest in very short (ultrahypofractionated) radiotherapy regimens to treat prostate cancer based on potential radiobiological advantages, patient convenience and resource allocation benefits. To demonstrate that... more
There is considerable interest in very short (ultrahypofractionated) radiotherapy regimens to treat prostate cancer based on potential radiobiological advantages, patient convenience and resource allocation benefits. To demonstrate that detectable changes in health related quality of life measured by the bowel and urinary domains of the Expanded Prostate Cancer Index Composite (EPIC-50) were not substantially worse than baseline. XXXX is a non-blinded randomized phase II study of NCCN low risk prostate cancer where each arm is compared to a historical control. Patients were randomized to five fractions (7.25Gy in two weeks), or twelve fractions (4.3Gy in 2.5 weeks). The co-primary endpoints were the proportion of patients with a change in EPIC bowel score at one year (baseline to one-year) >five points and in EPIC urinary score >two points tested with a one-sample binomial test. and Limitations: 127 patients were enrolled to five fractions (121 analyzed) and 128 to twelve frac...
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Trial RTOG 9202 was a phase 3 randomized trial designed to determine the optimal duration of androgen deprivation therapy (ADT) when combined with definitive radiation therapy (RT) in the treatment of locally advanced nonmetastatic... more
Trial RTOG 9202 was a phase 3 randomized trial designed to determine the optimal duration of androgen deprivation therapy (ADT) when combined with definitive radiation therapy (RT) in the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate. Long-term follow-up results of this study now available are relevant to the management of this disease. Men (N=1554) with adenocarcinoma of the prostate (cT2c-T4, N0-Nx) with a prostate-specific antigen (PSA) <150 ng/mL and no evidence of distant metastasis were randomized (June 1992 to April 1995) to short-term ADT (STAD: 4 months of flutamide 250 mg 3 times per day and goserelin 3.6 mg per month) and definitive RT versus long-term ADT (LTAD: STAD with definitive RT plus an additional 24 months of monthly goserelin). Among 1520 protocol-eligible and evaluable patients, the median follow-up time for this analysis was 19.6 years. In analysis adjusted for prognostic covariates, LTAD improved disease-free survival (29% rela...
Research Interests: Oncology, Prostate Cancer, Medicine, Humans, Internal Medicine, and 15 moreMale, Androgen Deprivation Therapy, Clinical Sciences, Aged, Middle Aged, Adult, Time Factors, Prostate Specific Antigen, Adenocarcinoma, Combined Modality Therapy, Disease Free Survival, Prostatic neoplasms, Flutamide, goserelin, and Androgen antagonists
... Mack Roach, III, David Reese, Vivian Weinberg, Eric J. Small, Peter R. Carroll. University of California, San Francisco San Francisco, CA. ... 5. Migliari R, Muscas G, Usai E: Effect of Casodex on sleep-related erections in patients... more
... Mack Roach, III, David Reese, Vivian Weinberg, Eric J. Small, Peter R. Carroll. University of California, San Francisco San Francisco, CA. ... 5. Migliari R, Muscas G, Usai E: Effect of Casodex on sleep-related erections in patients with advanced prostate cancer. ...
Research Interests: Oncology, Research Design, Quality of life, Treatment Outcome, Prostate Cancer, and 14 moreMedicine, Humans, Internal Medicine, Nitriles, Clinical, Male, Clinical oncology, Androgen Deprivation Therapy, Sample Size, Reproducibility of Results, Clinical Trials as Topic, Neoplasm staging, Prostatic neoplasms, and Androgen antagonists
The purpose of this study was to evaluate a receiver operating characteristic (ROC) curve method to determine dose thresholds with late genitourinary (GU) toxicity after stereotactic body radiation therapy for prostate cancer.... more
The purpose of this study was to evaluate a receiver operating characteristic (ROC) curve method to determine dose thresholds with late genitourinary (GU) toxicity after stereotactic body radiation therapy for prostate cancer. Seventy-eight patients diagnosed with low- to intermediate-risk prostate cancer and treated with stereotactic body radiation therapy alone were reviewed retrospectively. All patients received a total dose of 38 Gy in 4 fractions with a planning target volume expansion of 2 mm. GU toxicity was documented according to the Common Terminology Criteria for Adverse Events, version 4. ROC analysis applied on a logistic regression model was used to determine optimal dosimetric parameters for GU toxicity. The median age at treatment was 69 years with a median prostate volume of 46.2 mL. The median prescription isodose line was 67% (interquartile range, 65, 70). The median clinical follow-up was 35.49 months. Late grade 1, 2, and 3 GU toxicity occurred in 21.8%, 19.2%, ...
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Stereotactic body radiotherapy for prostate cancer is rapidly growing in popularity. Stereotactic body radiotherapy plans mimic those of high-dose rate brachytherapy, with tight margins and inhomogeneous dose distributions. The impact of... more
Stereotactic body radiotherapy for prostate cancer is rapidly growing in popularity. Stereotactic body radiotherapy plans mimic those of high-dose rate brachytherapy, with tight margins and inhomogeneous dose distributions. The impact of interfraction anatomical changes on the dose received by organs at risk under these conditions has not been well documented. To estimate anatomical variation during stereotactic body radiotherapy, 10 patients were identified who received a prostate boost using robotic stereotactic body radiotherapy after completing 25 fractions of pelvic radiotherapy with daily megavoltage computed tomography. Rectal and bladder volumes were delineated on each megavoltage computed tomography, and the stereotactic body radiotherapy boost plan was registered to each megavoltage computed tomography image using a point-based rigid registration with 3 fiducial markers placed in the prostate. The volume of rectum and bladder receiving 75% of the prescription dose (V75%) w...
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ABSTRACT
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High-dose-rate (HDR) brachytherapy alone is an effective treatment option for patients with early-stage prostate cancer. The purpose of this study was to quantify patient-reported short- and long-term toxicity and quality of life (QOL)... more
High-dose-rate (HDR) brachytherapy alone is an effective treatment option for patients with early-stage prostate cancer. The purpose of this study was to quantify patient-reported short- and long-term toxicity and quality of life (QOL) after HDR monotherapy. Thirty-nine consecutive men between May 2001 and January 2012 were identified for this analysis. All patients underwent definitive HDR monotherapy for favorable prostate cancer to a total dose of 3150 cGy in three fractions, 3800 cGy in four fractions, or 3850 in five fractions. Patient-reported genitourinary function was assessed before HDR, during an acute period after treatment (within 90 days of HDR), and on long-term followup using the American Urological Association International Prostate Symptom Score, a urinary QOL Likert questionnaire, and the Sexual Health Inventory for Men questionnaire. Regression analyses were performed using the ordinary least squares method. With median followup of 57 months, biochemical progression-free survival was 100%. There were no grade ≥3 toxicities. Dose to the urethra and bladder, as well as prostate size and intraprostatic urethra length were predictive for short-term changes in QOL. Advanced patient age was predictive for worse sexual function on both acute and long-term followup. Toxicity after HDR monotherapy for prostate cancer is acceptable. Patients with larger prostates, longer intraprostatic urethras, and greater doses to the bladder and urethra may experience worse acute urinary QOL. Older patients may experience greater impairment in sexual function in the short and long terms.
Research Interests: Urology, Quality of life, Brachytherapy, Prostate Cancer, Medicine, and 15 moreHumans, Internal Medicine, Male, Follow-up studies, Prostate, Clinical Sciences, Aged, Middle Aged, Age Factors, Prostate Specific Antigen, Urinary Bladder, Surveys and Questionnaires, Urogenital System, Disease Free Survival, and Prostatic neoplasms
In this issue of European Urology, Sineshaw et al [1] report the results of a retrospective analysis of nearly 100 000 patients managed with radical prostatectomy (RP) for prostate cancer (PCa), all of whom had extracapsular extension of... more
In this issue of European Urology, Sineshaw et al [1] report the results of a retrospective analysis of nearly 100 000 patients managed with radical prostatectomy (RP) for prostate cancer (PCa), all of whom had extracapsular extension of the disease (pT3–T4) and/or positive surgical margins according to postoperative pathology. The authors’ main objective was to describe changes in practice patterns that may have occurred after the publication of results from three large randomized clinical trials (RCTs)—by the Southwest Oncology Group (SWOG), Arbeitsgemeinschaft Radiologische Onkologie (ARO), and the European Organisation for Research and Treatment of Cancer (EORTC)—demonstrating that immediate postoperative radiotherapy (RT) of the post-RP tumor bed in patients with such adverse features reduces the risk of biochemical relapse and the need for subsequent androgen deprivation therapy (ADT) and, at least in one of the RCTs, decreases the risk of developing clinical recurrence and distant metastasis, and ultimately improves survival [2–4]. With a growing number of patients currently undergoing surgery as the primary treatment option for high-risk or very high-risk PCa (cT3–4, prostate-specific antigen [PSA] >20 ng/ml, biopsy Gleason score > 3 + 4), the relative merits of postoperative adjuvant treatment (RT or ADT) is becoming a central issue. Let us first set the scene. A study in a contemporary series of 2065 patients with high-risk PCa treated by RP alone in seven high-volume tertiary referral centers revealed that approximately 50% will develop biochemical recurrence by 5 yr [5]. Few data, if any, have been reported on the corresponding incidence for lowvolume hospitals and less experienced surgeons. Acknowledging the impact of the learning curve for surgery in the high-risk setting, we suspect that this incidence may be even higher. Moreover, the argument claiming the possible innocent nature of a PSA rise after surgery (according to which, not all increasing PSA levels will translate into a significant impact on endpoints such as overall survival and cancer-specific survival) is less defensible in the context of (very) high-risk disease, especially if biochemical relapse occurs early during follow-up. It is noteworthy that multivariate analysis clearly demonstrated a significant association between (early) biochemical recurrence and the risk of dying from PCa [5]. The bottom line is that, at least for high-risk patients undergoing RP, biochemical recurrence is probably a key determinant of subsequent major events. Several studies analyzing huge databases or smaller cohorts of patients have already shown that the use of postRP RT has not increased in recent years; on the contrary, it has gradually declined, and the publication in 2009 of results for the SWOG trial and of early results for the ARO trial did not modify this trend [6]. Thus, it is not surprising that Sineshaw et al found a similar decrease between 2005 and 2011 in a large US clinical database: only 7.3% of patients received post-RP RT in 2011, compared to 9.1% in 2005. Even the subgroup of patients with the least favorable prognostic factors (age <60 yr, pT3–T4 disease with a positive margin and Gleason 8–10) and no comorbidities only received postoperative RT one third of the time. The EU RO P E AN URO LOGY 6 8 ( 2 0 1 5 ) 7 7 5 – 7 7 6
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The first St.Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer management. The successful... more
The first St.Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection.Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior...
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Treatment plans for prostate cancer patients undergoing stereotactic body radiation therapy (SBRT) are often challenging due to the proximity of organs at risk. Today, there are no objective criteria to determine whether an optimal... more
Treatment plans for prostate cancer patients undergoing stereotactic body radiation therapy (SBRT) are often challenging due to the proximity of organs at risk. Today, there are no objective criteria to determine whether an optimal treatment plan has been achieved, and physicians rely on their personal experience to evaluate the plan's quality. In this study, we propose a method for determining rectal and bladder dose constraints achievable for a given patient's anatomy. We expect that this method will improve the overall plan quality and consistency, and facilitate comparison of clinical outcomes across different institutions. The 3D proximity of the organs at risk to the target is quantified by means of the expansion-intersection volume (EIV), which is defined as the intersection volume between the target and the organ at risk expanded by 5 mm. We determine a relationship between EIV and relevant dosimetric parameters, such as the volume of bladder and rectum receiving 75%...
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Radium-223 is a promising agent that represents a new class of alpha pharmaceuticals that gets down to the site of bony metastases. The limited side-effect profile potentially allows for repeat administration to increase durability of... more
Radium-223 is a promising agent that represents a new class of alpha pharmaceuticals that gets down to the site of bony metastases. The limited side-effect profile potentially allows for repeat administration to increase durability of pain control, and for its use in combination with novel biologic and chemotherapeutic agents.
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Prostate cancer screening using prostate-specific antigen (PSA) testing has been a contentious subject.
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Prostate cancer is diagnosed in younger men who want treatment that does not compromise their quality of life, take time away from work, or cause worrisome side effects. Laparoscopic radical prostatectomy, robot-assisted laparoscopic... more
Prostate cancer is diagnosed in younger men who want treatment that does not compromise their quality of life, take time away from work, or cause worrisome side effects. Laparoscopic radical prostatectomy, robot-assisted laparoscopic radical prostatectomy, and third-generation cryotherapy are modifications of previously used techniques in the treatment of prostate cancer and are presented in this article. Although some or all of the outcomes might be expected to change in the future, the urologic surgeon is left to select an approach, presumably on the basis of the experience, level of training, and care pathways at his or her institution.
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Several prospective randomized trials have demonstrated that men with localized prostate cancer benefit from the use of short-term neoadjuvant hormonal therapy (NHT) in combination with external beam radiotherapy (EBRT). Seven randomized... more
Several prospective randomized trials have demonstrated that men with localized prostate cancer benefit from the use of short-term neoadjuvant hormonal therapy (NHT) in combination with external beam radiotherapy (EBRT). Seven randomized trials were summarized in 6 publications including patients treated with NHT in combination with EBRT on 1 or more arms. A total of 17 different arms were compared including radiotherapy alone (n = 3), and NHT and concurrent hormonal therapy (N&CHT) (n = 12) with or without short-term adjuvant hormonal therapy (SAHT) (n = 5) or long-term hormonal therapy (n = 1). Patients treated with EBRT alone had a worse outcome than those treated with NHT. Intermediate-risk patients treated with 2 to 3 months of NHT did as well as those treated with longer neoadjuvant therapy or SAHT. The preponderance of data supports the use of NHT in combination with EBRT in intermediate-risk patients.
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The use of hormonal therapy with external-beam radiation (EBRT) to treat prostate cancer is a topic that has been well explored. The potential use of hormonal therapy and brachytherapy in the treatment of prostate cancer, however,... more
The use of hormonal therapy with external-beam radiation (EBRT) to treat prostate cancer is a topic that has been well explored. The potential use of hormonal therapy and brachytherapy in the treatment of prostate cancer, however, continues to be controversial. This review is based on our current interpretation of the available literature assessing the outcomes of patients treated with EBRT and brachytherapy with or without hormonal therapy. Extrapolating from the findings of the Radiation Therapy Oncology Group (RTOG) 9413 trial, there appears to be a favorable interaction between hormonal therapy and irradiation in the lymph nodes. The benefits demonstrated with whole-pelvic EBRT and hormonal therapy are likely to extend to patients treated with brachytherapy as well. Studies suggest that the role of hormonal therapy in brachytherapy is limited without the application of whole-pelvic EBRT due to the inability of brachytherapy to address potential lymph nodes at risk. The potential...
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The risk for serious complications associated with modern radiotherapy is relatively low. Compared with conventional radiotherapy, 3DCRT and IMRT allow higher doses to be given more safely. The use of IMRT increases the time and effort... more
The risk for serious complications associated with modern radiotherapy is relatively low. Compared with conventional radiotherapy, 3DCRT and IMRT allow higher doses to be given more safely. The use of IMRT increases the time and effort required by physicians and physicists. Although there is a clear move toward IMRT, 3DCRT is considered standard. The quality assurance procedures for and fundamental questions regarding IMRT are evolving, including the radiobiologic consequences of altered time-dose fractionation and the greater dose heterogeneity in the target. Defining an accurate target volume and routinely correcting for set-up error and organ movement before each treatment promise to reduce the complications associated with EBRT in the next 5 years. Complications following prostate brachytherapy are better understood now than 10 years ago. Dosimetric or patient selection factors that correlate with a higher risk for complications, such as acute retention, strictures, severe prolo...
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Plasma cell tumors are monoclonal tumors of immunoglobulin-secreting cells, derived from B-cell lymphocytes. Incidence is low overall, ∼1–2% of U.S. cancers diagnosed yearly are plasma cell tumors. More than 90% of these are multiple... more
Plasma cell tumors are monoclonal tumors of immunoglobulin-secreting cells, derived from B-cell lymphocytes. Incidence is low overall, ∼1–2% of U.S. cancers diagnosed yearly are plasma cell tumors. More than 90% of these are multiple myeloma (MM); ∼2–10% are solitary plasmacytoma (SP). MM incidence higher in blacks than whites (∼2:1). Median age at diagnosis 70 years. SP more common in men than women (4:1). Median age at diagnosis 50–55 years. Etiology is unknown, may involve occupational exposures, RT, solvents (Nau et al. 2008). 20% of patients are free of clinical symptoms at diagnosis. Osseous SP and MM may manifest as bone pain, neurologic symptoms, pathologic fracture, cord compression, anemia, hypercalcemia, renal insufficiency (Schechter et al. 2003).
Prostate cancer and its management have been intensely debated for years. Recommendations range from ardent support for active screening and immediate treatment to resolute avoidance of screening and active surveillance. There is a... more
Prostate cancer and its management have been intensely debated for years. Recommendations range from ardent support for active screening and immediate treatment to resolute avoidance of screening and active surveillance. There is a growing body of level I evidence establishing a clear survival advantage for treatment of subsets of patients with clinically localized prostate cancer. This chapter presents a review of these randomized controlled trials. We argue that an understanding of this literature is relevant not only to those considering active surveillance but also to those evaluating the merits of screening. In addition, a number of important evidence-based conclusions concerning what should and should not be done can be gleaned from these trials.