Adjuvant radiation therapy, androgen deprivation, and docetaxel for high-risk prostate cancer postprostatectomy: Results of NRG Oncology/RTOG study 0621.

BACKGROUND: Phase 3 trials have demonstrated a benefit from adjuvant radiation therapy (ART) for men who have adverse factors at radical prostatectomy (RP). However, some patients have a high risk of progression despite ART. The role of systemic therapy with ART in this high-risk group remains to be defined. METHODS: Patients who had either a post-RP prostate-specific antigen (PSA) nadir > 0.2 ng/mL and a Gleason score ≥7 or a PSA nadir ≤0.2 ng/mL, a Gleason score ≥8, and a pathologic tumor (pT) classification ≥ pT3 received 6 months of androgen-deprivation therapy (ADT) plus radiotherapy and 6 cycles of docetaxel. The primary objective was to assess whether the addition of ADT and docetaxel to ART resulted in a freedom from progression (FFP) rate ≥ 70% compared with an expected rate of 50%. Multivariate logistic and Cox regression analyses were used to model associations between factors and outcomes. RESULTS: In total, 74 patients were enrolled. The median follow-up was 4.4 years. The pathologic tumor classification was pT2 in 4% of patients, pT3 in 95%, and pT4 in 1%. The Gleason score was 7 in 18% of patients and ≥8 in 82%. Post-RP PSA levels were ≤0.2 ng/mL in 53% of patients and >0.2 ng/mL in 47%. The 3-year FFP rate was 73% (95% confidence interval, 61%-83%), and the 3-year cumulative incidence of biochemical, distant, and local failure was 26%, 7%, and 0%, respectively. In multivariate models, postprostatectomy PSA nadir was associated with 3-year FFP, Gleason score, and PSA with biochemical failure. Grade 3 and 4 neutropenia was common; however, only 3 episodes of febrile neutropenia occurred. Late toxicities were not impacted by the addition of systemic therapy. CONCLUSIONS: Combined ADT, docetaxel, and ART for men with high-risk prostate cancer after prostatectomy exceeded the prespecified study endpoint of 70% 3-year FFP. Phase 3 trials assessing combined local and systemic therapies for these high-risk patients are warranted. Cancer 2017;123:2489-96. © 2017 American Cancer Society.

Structure and Mechanisms of SF2 DNA Helicases.

Effective transcription, replication, and maintenance of the genome require a diverse set of molecular machines to perform the many chemical transactions that constitute these processes. Many of these machines use single-stranded nucleic acids as templates, and their actions are often regulated by the participation of nucleic acids in multimeric structures and macromolecular assemblies that restrict access to chemical information. Superfamily II (SF2) DNA helicases and translocases are a group of molecular machines that remodel nucleic acid lattices and enable essential cellular processes to use the information stored in the duplex DNA of the packaged genome. Characteristic accessory domains associated with the subgroups of the superfamily direct the activity of the common motor core and expand the repertoire of activities and substrates available to SF2 DNA helicases, translocases, and large multiprotein complexes containing SF2 motors. In recent years, single-molecule studies have contributed extensively to the characterization of this ubiquitous and essential class of enzymes.

Effect of Brachytherapy With External Beam Radiation Therapy Versus Brachytherapy Alone for Intermediate-Risk Prostate Cancer: NRG Oncology RTOG 0232 Randomized Clinical Trial.

PURPOSE: To determine whether addition of external beam radiation therapy (EBRT) to brachytherapy (BT) (COMBO) compared with BT alone would improve 5-year freedom from progression (FFP) in intermediate-risk prostate cancer. METHODS: Men with prostate cancer stage cT1c-T2bN0M0, Gleason Score (GS) 2-6 and prostate-specific antigen (PSA) 10-20 or GS 7, and PSA < 10 were eligible. The COMBO arm was EBRT (45 Gy in 25 fractions) to prostate and seminal vesicles followed by BT prostate boost (110 Gy if 125-Iodine, 100 Gy if 103-Pd). BT arm was delivered to prostate only (145 Gy if 125-Iodine, 125 Gy if 103-Pd). The primary end point was FFP: PSA failure (American Society for Therapeutic Radiology and Oncology [ASTRO] or Phoenix definitions), local failure, distant failure, or death. RESULTS: Five hundred eighty-eight men were randomly assigned; 579 were eligible: 287 and 292 in COMBO and BT arms, respectively. The median age was 67 years; 89.1% had PSA < 10 ng/mL, 89.1% had GS 7, and 66.7% had T1 disease. There were no differences in FFP. The 5-year FFP-ASTRO was 85.6% (95% CI, 81.4 to 89.7) with COMBO compared with 82.7% (95% CI, 78.3 to 87.1) with BT (odds ratio [OR], 0.80; 95% CI, 0.51 to 1.26; Greenwood T P = .18). The 5-year FFP-Phoenix was 88.0% (95% CI, 84.2 to 91.9) with COMBO compared with 85.5% (95% CI, 81.3 to 89.6) with BT (OR, 0.80; 95% CI, 0.49 to 1.30; Greenwood T P = .19). There were no differences in the rates of genitourinary (GU) or GI acute toxicities. The 5-year cumulative incidence for late GU/GI grade 2+ toxicity is 42.8% (95% CI, 37.0 to 48.6) for COMBO compared with 25.8% (95% CI, 20.9 to 31.0) for BT (P < .0001). The 5-year cumulative incidence for late GU/GI grade 3+ toxicity is 8.2% (95% CI, 5.4 to 11.8) compared with 3.8% (95% CI, 2.0 to 6.5; P = .006). CONCLUSION: Compared with BT, COMBO did not improve FFP for prostate cancer but caused greater toxicity. BT alone can be considered as a standard treatment for men with intermediate-risk prostate cancer.

Kinetic basis of sugar selection by a Y-family DNA polymerase from Sulfolobus solfataricus P2.

DNA polymerases use either a bulky active site residue or a backbone segment to select against ribonucleotides in order to faithfully replicate cellular genomes. Here, we demonstrated that an active site mutation (Y12A) within Sulfolobus solfataricus DNA polymerase IV (Dpo4) caused an average increase of 220-fold in matched ribonucleotide incorporation efficiency and an average decrease of 9-fold in correct deoxyribonucleotide incorporation efficiency, leading to an average reduction of 2000-fold in sugar selectivity. Thus, the bulky side chain of Tyr12 is important for both ribonucleotide discrimination and efficient deoxyribonucleotide incorporation. Other than synthesizing DNA as the wild-type Dpo4, the Y12A Dpo4 mutant incorporated more than 20 consecutive ribonucleotides into primer/template (DNA/DNA) duplexes, suggesting that this mutant protein possesses both a DNA-dependent DNA polymerase activity and a DNA-dependent RNA polymerase activity. Moreover, the binary and ternary crystal structures of Dpo4 have revealed that this DNA lesion bypass polymerase can bind up to eight base pairs of double-stranded DNA which is entirely in B-type. Thus, the DNA binding cleft of Dpo4 is flexible and can accommodate both A- and B-type oligodeoxyribonucleotide duplexes as well as damaged DNA.

A novel, adaptable, radiographically opaque, multi-plane continuous filament marker for optimizing tissue identification, radiation planning, and radiographic follow-up.

BACKGROUND: In breast cancer treatment, marking the tumor bed is an important aspect of the surgical component of therapy. Clear delineation of the tumor bed allows radiation oncologists a defined target for planning and delivering postoperative radiation therapy (XRT). Tumor bed marking also allows radiographic follow-up of the tumor bed on subsequent breast imaging. The aim of this assessment is to evaluate the ease and feasibility of utilizing a tumor bed filament marker (VeraFormÒ, Videra Surgical inc., USA) as a marker in post-operative benign surgical sites and malignant breast surgical tumor beds in breast cancer surgery. METHODS: The filament marker is a novel radiopaque surgical filament that in lieu of clips and other markers is implanted in the surgical tumor bed during breast surgery. Following development of the filament marker, the researchers used breast phantoms and radiographic images to develop a series of geometric patterns of placement options that optimize comprehensive multi-plane radiographic interpretation of the exact tumor bed or surgical margin. Three breast surgeons at 3 separate institutions then used this filament as a continuous multi-plane marker in 20 patients during breast conservation surgery. In these patients, the filament marker was thus used to mark the tumor bed (breast cancer surgery) or surgical site (benign breast disease) instead of the more traditional devices such as clips or other metallic open framework devices. We then assessed 2 important factors related to this device; (I) the ease, feasibility, and accuracy of in vivo placement with oncoplastic and non-oncoplastic breast conservation surgery techniques; (II) the radiographic footprint this device left on standard imaging protocols of post-operative mammogram (MMG), computed tomography (CT) scan, breast magnetic resonance imaging (MRI) examinations, and ultrasounds (USs) for both routine follow-up imaging and for standard radiation planning. RESULTS: There were no adverse events reported with the use of this device. The cases were then reviewed by a multidisciplinary team that included the original surgeon, a breast radiologist, and radiation oncologist. Their unanimous evaluation was that the filament marker clearly delineated all sides and planes of the tumor bed (cancer surgery) or surgical site (benign disease). Regardless of surgical technique utilized, this information provided precise 3D guidance for radiation planning and delivery as well as radiographic follow-up. The surgeons involved reported that delineating the bed with the filament marker was a quick and easy procedure and did not interfere with performing the planned surgical technique. Radiologists, surgeons, and radiation oncologists found that the filament marker was not only radiographically opaque on CT and MMG, but also caused no significant artifact on CT, MRI, US, or MMG. CONCLUSIONS: The continuous multi-plane filament marker is a new device that fulfills the heretofore unmet need for safe and improved tumor bed and tissue site marking. It is an easy to place, non-palpable continuous multi-plane radiographic opaque tissue marker that seems to better delineate the tumor bed, regardless of type of breast surgery performed, while providing a more accurate 3D image for radiation planning and radiographic follow-up on MMG MRI, CT and US.

Patient Reported Outcomes in NRG Oncology RTOG 0938, Evaluating Two Ultrahypofractionated Regimens for Prostate Cancer.

PURPOSE: There is considerable interest in very short (ultrahypofractionated) radiation therapy regimens to treat prostate cancer based on potential radiobiological advantages, patient convenience, and resource allocation benefits. Our objective is 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 scores. METHODS AND MATERIALS: NRG Oncology's RTOG 0938 is a nonblinded randomized phase 2 study of National Comprehensive Cancer Network low-risk prostate cancer in which each arm is compared with a historical control. Patients were randomized to 5 fractions (7.25 Gy in 2 weeks) or 12 fractions (4.3 Gy in 2.5 weeks). The co-primary endpoints were the proportion of patients with a change in EPIC-50 bowel score at 1 year (baseline to 1 year) >5 points and in EPIC-50 urinary score >2 points tested with a 1-sample binomial test. RESULTS: The study enrolled 127 patients to 5 fractions (121 analyzed) and 128 patients to 12 fractions (125 analyzed). Median follow-up for all patients at the time of analysis was 3.8 years. The 1-year frequency for >5 point change in bowel score were 29.8% (P < .001) and 28.4% (P < .001) for 5 and 12 fractions, respectively. The 1-year frequencies for >2 point change in urinary score were 45.7% (P < .001) and 42.2% (P < .001) for 5 and 12 fractions, respectively. For 5 fractions, 32.9% of patients had a drop in 1-year EPIC-50 sexual score of ≥11 points (P = .34); for 12 fractions, 30.9% of patients had a drop in 1-year EPIC-50 sexual score of ≥ 11 points (P = .20). Disease-free survival at 2 years is 99.2% (95% confidence interval: 97.5-100) in the 5-fraction arm and 97.5% (95% confidence interval: 94.6-100) in the 12-fraction arm. There was no late grade 4 or 5 treatment-related urinary or bowel toxicity. CONCLUSIONS: This study confirms that, based on changes in bowel and urinary domains and toxicity (acute and late), the 5- and 12-fraction regimens are well tolerated. These ultrahypofractionated approaches need to be compared with current standard radiation therapy regimens.

Multi-institutional analysis of long-term outcome for stages T1-T2 prostate cancer treated with permanent seed implantation.

PURPOSE: To assess long-term prostate-specific antigen (PSA) outcome after permanent prostate brachytherapy (BT) and identify predictors of improved disease-free survival. METHODS AND MATERIALS: Eleven institutions combined data on 2,693 patients treated with permanent interstitial BT monotherapy for T1-T2 prostate cancer. Of these patients, 1,831 (68%) were treated with I-125 (median dose, 144 Gy) and 862 (32%) were treated with Pd-103 (median dose, 130 Gy). Criteria for inclusion were: available pre-BT PSA, BT > or =5 years before data submission, BT between 1988-1998, and no androgen deprivation before failure. The median follow-up was 63 months. RESULTS: Among patients where the I-125 dose to 90% of the prostate (D90) was > or =130 Gy, the 8-year PSA relapse-free survival (PRFS) was 93% compared with 76% for those with lower D90 dose levels (p < 0.001). A multivariable analysis identified tumor stage (p = 0.002), Gleason score (p < 0.001), pretreatment PSA level (p < 0.001), treatment year (p = 0.001), and the isotope used (p = 0.004) as pretreatment and treatment variables associated with PRFS. When restricted to patients with available postimplantation dosimetric information, D90 emerged as a significant predictor of biochemical outcome (p = 0.01), and isotope was not significant. The 8-year PRFS was 92%, 86%, 79%, and 67%, respectively, for patients with PSA nadir values of 0-0.49, 0.5-0.99, 1.0-1.99, and >2.0 ng/mL (p < 0.001). Among patients free of biochemical relapse at 8 years, the median nadir level was 0.1 ng/mL, and 90% of these patients achieved a nadir PSA level <0.6 ng/mL. CONCLUSIONS: Outcome after permanent BT for prostatic cancer relates to tumor stage, Gleason score, pretreatment PSA, BT year, and post-BT dosimetric quality. PSA nadir < or =0.5 ng/mL was particularly associated with durable long-term PSA disease-free survival. The only controllable factor to impact on long-term outcome was the D90 which is a reflection of implant quality.

Interstitial implant alone or in combination with external beam radiation therapy for intermediate-risk prostate cancer: a survey of practice patterns in the United States.

PURPOSE: This study is aimed at understanding and defining the current patterns of care with respect to prostate brachytherapy for patients with intermediate-risk localized disease in the combined academic and community setting. METHODS AND MATERIALS: A nomogram-based survey was developed at the Seattle Prostate Institute defining the accepted criteria for intermediate-risk prostate cancer. Patients were defined as having intermediate-risk prostate cancer if they met one of the following criteria: prostate-specific antigen (PSA) >10 ng/dL, Gleason score (GS) > or = 7, or cT2b or cT2c disease. Additional potential predictive factors including perineural invasion (PNI), GS 3+4 vs. 4+3, and high-volume disease were included. RESULTS: In the absence of PNI, all of those surveyed would perform monotherapy for intermediate-risk patients, GS 7 (3+4) or PSA 10-20, with cT1c and <30% cores +. Up to 80% would perform monotherapy for patients with cT1c, GS 7 (4+3), and <30% cores +. Eighty to 90% of physicians would perform an implant alone with cT2a and either a PSA of 10-20 or GS of 7 (3+4) and <30% cores +. Fifty to 60% of those surveyed stated that they would treat a patient with cT2b disease, GS 7 (3+4), or PSA 11-20, with less than two-thirds of the biopsy cores positive in the absence of PNI. CONCLUSIONS: This Patterns of Care (POC) study reveals that certain subsets of intermediate-risk localized prostate cancer patients are considered appropriate candidates for an interstitial implant alone.

Comparison of biochemical failure definitions for permanent prostate brachytherapy.

PURPOSE: To assess prostate-specific antigen (PSA) failure definitions for patients with Stage T1-T2 prostate cancer treated by permanent prostate brachytherapy. METHODS AND MATERIALS: A total of 2,693 patients treated with radioisotopic implant as solitary treatment for T1-T2 prostatic adenocarcinoma were studied. All patients had a pretreatment PSA, were treated at least 5 years before analysis, 1988 to 1998, and did not receive hormonal therapy before recurrence. Multiple PSA failure definitions were tested for their ability to predict clinical failure. RESULTS: Definitions which determined failure by a certain increment of PSA rise above the lowest PSA level to date (nadir + x ng/mL) were more sensitive and specific than failure definitions based on PSA doubling time or a certain number of PSA rises. The sensitivity and specificity for the nadir + 2 definition were 72% and 83%, vs. 51% and 81% for 3 PSA rises. The surgical type definitions (PSA exceeding an absolute value) could match this sensitivity and specificity but only when failure was defined as exceeding a PSA level in the 1-3 ng/mL range and only when patients were allowed adequate time to nadir. When failure definitions were compared by time varying covariate regression analysis, nadir + 2 ng/mL retained the best fit. CONCLUSIONS: For patients treated by permanent radioisotopic implant for prostate cancer, the definition nadir + 2 ng/mL provides the best surrogate for failure throughout the entire follow-up period, similar to patients treated by external beam radiotherapy. Therefore, the same PSA failure definition could be used for both modalities. For brachytherapy patients with long-term follow-up, at least 6 years, defining failure as exceeding an absolute PSA level in the 0.5 ng/mL range may be reasonable.

Hydrogel Spacer Application Technique, Patient Tolerance and Impact on Prostate Intensity Modulated Radiation Therapy: Results from a Prospective, Multicenter, Pivotal Randomized Controlled Trial.

INTRODUCTION: We evaluate the safety, tolerability and impact on therapy of an absorbable hydrogel perirectal spacer (SpaceOAR® system) designed to reduce the rectal radiation dose during prostate cancer radiotherapy. METHODS: A multicenter, pivotal, randomized controlled trial was conducted in 222 men with stage T1 or T2 prostate cancer treated to 79.2 Gy with image guided intensity modulated radiation therapy in 44 fractions. Patients were randomized 2:1 to receive fiducial markers and perirectal spacer injection (spacer group) or fiducial markers alone (control group). Spacer placement, tolerability, perirectal space creation, impact on rectal dose and impact on quality of life were assessed. RESULTS: Most spacer procedures were conducted with the patient under general or local anesthesia. Procedures were rated easy or very easy in 98.7% of cases with a 99.3% success rate. Mild transient rectal events were noted in 10% of patients in the spacer group (eg pain, discomfort). Mean perirectal space was 12.6 mm after implant and 10.9 mm at 12.4 weeks with absorption at 12 months. A 25% or greater reduction in rectal V70 dose was produced in 97.3% of patients in the spacer group. The spacer group experienced a significant reduction in late rectal toxicity severity (p=0.044) as well as lower rates of decrease in bowel quality of life at 6, 12 and 15 months compared to the control group. There were no unanticipated adverse spacer effects or spacer related adverse events. CONCLUSIONS: Hydrogel spacer application was straightforward and repeatable, resulting in consistent perirectal space creation and rectal dose reduction. Spacer application has the potential to improve prostate radiotherapy outcomes and enable advanced radiotherapy protocols.

Impact of short course hormonal therapy on overall and cancer specific survival after permanent prostate brachytherapy.

PURPOSE: To review the impact of prior hormonal therapy on 10-year overall and prostate cancer specific survival after primary brachytherapy. METHODS AND MATERIALS: A retrospective review was performed on the Arizona Oncology Services tumor registry for 2,378 consecutive permanent prostate brachytherapy cases from 1988 through 2001. Hormonal therapy was administered before the implant in 464 patients for downsizing of the prostate or at the discretion of the referring physician. All deceased patients with known clinical recurrence were considered to have died of prostate cancer, irrespective of the immediate cause of death. Risk groups were defined, with 1,135 favorable (prostate-specific antigen [PSA] < 10, Gleason < 7, Stage T1-T2a), 787 intermediate (single adverse feature), and 456 unfavorable (two or more adverse features) patients. Kaplan-Meier actuarial survival curves were generated for both overall and cause-specific survival from the time of treatment. Multivariate analysis was performed to assess the impact of hormonal intervention in comparison with known risk factors of grade, PSA, and age. RESULTS: With follow-up ranging up to 12.6 years and a median of 4.1 year, a total of 474 patients died, with 67 recorded as due to prostate cancer. Overall and cause-specific 10-year survival rates are 43% and 88%, respectively. Overall survival is 44% for the hormone naive patients, compared with 20% for the hormone-treated cohort (p = 0.02). The cancer-specific survival is 89% vs. 81% for the same groups (p = 0.133). Multivariate analysis confirms the significance of age > 70 years (p = 0.0013), Gleason score >/= 7 (p = 0.0005), and prior hormone use (p = 0.0065) on overall survival. CONCLUSIONS: At 10 years, in prostate cancer patients receiving brachytherapy, overall survival is worse in men receiving neoadjuvant hormonal therapy, compared with hormone naive patients. This does not appear to be due to other known risk factors for survival (i.e., stage, grade, PSA, age) on multivariate analysis. The leading causes of death were cardiovascular, prostate cancer, and other cancers with no obvious discrepancy between the two groups. This finding is unexpected and requires confirmation from other centers.

Brachytherapy for recurrent prostate cancer after radiation therapy.

Prostate cancer specialists routinely see patients with recurrent disease after external beam irradiation. Traditionally, only palliative treatments have been offered with hormonal intervention or simple observation. A significant, although as yet uncertain, percentage of these patients will have only locally recurrent cancer and thus are potentially candidates for curative salvage therapy. Permanent brachytherapy with (125)I or (103)Pd has been used in an attempt to eradicate the remaining prostate cancer and prevent the need for additional intervention. It is particularly critical in this population to identify those patients most likely to have distant metastases or who are unlikely to suffer death or morbidity from their local recurrence to avoid potential treatment morbidity in patients unlikely to benefit from any intervention. Review of the literature shows 5-year freedom from second relapse after salvage brachytherapy in approximately 50% of patients, although with careful case selection second relapse free survival rates of up to 83% may be achieved. A schema is presented, based on the available data, suggesting that it may be possible to identify those patients who are most likely to benefit from salvage treatment. These include men with the following: (1) histologically confirmed local recurrence, (2) no clinical or radiologic evidence of distant disease, (3) adequate urinary function (IPSS < 20), (4) age and overall health indicative of >5- to 10-year life expectancy, (5) prolonged disease-free interval (>2 years) from primary radiation therapy, (6) long prostate-specific antigen (PSA) doubling time (>6-9 months), (7) Gleason sum

Salvage brachytherapy after external-beam irradiation for prostate cancer.

The options available for patients with recurrent prostate cancer are limited. Men who have failed external-beam irradiation as the primary treatment are rarely considered for potentially curative salvage therapy. Traditionally, only palliative treatments have been offered with hormonal intervention or simple observation. A significant percentage of these patients have only locally recurrent cancer and are thus candidates for curative salvage therapy. Permanent brachytherapy with iodine-125 or palladium-103 has been used in an attempt to eradicate the remaining prostate cancer and prevent the need for additional intervention. It is critical in this population to identify patients most likely to have distant metastases or who are unlikely to suffer death or morbidity from their recurrence, in order to avoid potential treatment morbidity in those unlikely to benefit from any intervention. Following salvage brachytherapy, up to 98% of these cancers may be locally controlled, and 5-year freedom from second relapse is approximately 50%. With careful case selection, relapse-free rates up to 83% may be achieved. A schema is presented, suggesting that it may be possible to identify the patients most likely to benefit from salvage treatment based on prostate-specific antigen (PSA) kinetics and other features. Such features include histologically confirmed local recurrence, clinical and radiologic evidence of no distant disease, adequate urinary function, age, and overall health indicative of at least a 5- to 10-year life expectancy, prolonged disease-free interval (> 2 years), slow PSA doubling time, Gleason sum < or = 6, and PSA < 10 ng/mL.

Relative influence of Gleason score and pretreatment PSA in predicting survival following brachytherapy for prostate cancer.

PURPOSE: To evaluate 10-year survival rates after prostate brachytherapy and to assess the relative importance of pretreatment prostate-specific antigen (PSA) and Gleason score in predicting cancer death. MATERIALS AND METHODS: A retrospective review was performed on all patients treated with permanent brachytherapy for stage T1 or T2 primary prostate cancer at a single institution from December 1988 through June 30, 1998. The study cohort consisted of 1266 patients with a median follow-up of 4.1 years and a maximum of 12.6 years. Actuarial survival and cause-specific survival rates were calculated as the primary endpoints, and compared at 5 and 10 years. Groups studied consist of PSAor=10 as well as Gleason 2-4, 5-6, and 7-10. Multivariate and univariate analysis were performed looking at stage, grade, PSA, and risk group as variables. RESULTS: The median age at the time of treatment was 73 years and at the time of analysis 603 patients were known to be alive. Overall survival is 38% at 10 years, however most deaths were unrelated to prostate cancer. Cause specific survival at 5 and 10 years is 98% and 87%. Both grade (>or=Gleason 7) and PSA (>or=10 ng/ml) predict adversely for cancer death within 10 years. Patients with low grade or PSA at presentation reveal prostate cancer-specific survival of 91% and 98%, respectively. By contrast, men with high grade or high PSA presentation have survival of 66% and 69% at 10 years. In multivariate analysis, the presence of one of these adverse features carries a hazard ratio of cancer death of 4.7 and 6.4, while the presence of multiple risk factors places patients in an unfavorable risk group with a hazard ratio of 27. CONCLUSIONS: Biochemical disease-free survival is a useful tool to assess prostate cancer treatments and is predicted based on established pretreatment risk groups. Long-term cancer-specific survival is ultimately a more important endpoint. Brachytherapy is reported here to be an excellent therapeutic alternative for selected early stage patients with prostate cancer. This is based on 10-year cause specific survival, which may also be predicted by stage, grade, PSA, and risk group. Of these, the risk group remains the most powerful parameter to identify those patients at highest risk of biochemical failure and death from prostate cancer.

American College of Radiology (ACR) and American Society for Radiation Oncology (ASTRO) Practice Guideline for Intensity-modulated Radiation Therapy (IMRT).

Intensity-modulated radiation therapy (IMRT) is a complex technique for the delivery of radiation therapy preferentially to target structures while minimizing doses to adjacent normal critical structures. It is widely utilized in the treatment of a variety of clinical indications in radiation oncology, including tumors of the central nervous system, head and neck, breast, prostate, gastrointestinal tract, and gynecologic organs, as well as in situations where previous radiation therapy has been delivered, and has allowed for significant therapeutic advances in many clinical areas. IMRT treatment planning and delivery is a complex process. Safe and reliable delivery of IMRT requires appropriate process design and adherence to quality assurance (QA) standards. A collaborative effort of the American College of Radiology and American Society for Therapeutic Radiation Oncology has produced a practice guideline for IMRT. The guideline defines the qualifications and responsibilities of all the involved personnel, including the radiation oncologist, physicist, dosimetrist, and radiation therapist. Factors with respect to the QA of the treatment planning system, treatment-planning process, and treatment-delivery process are discussed, as are issues related to the utilization of volumetric modulated arc therapy. Patient-specific QA procedures are presented. Successful IMRT programs involve integration of many processes: patient selection, patient positioning/immobilization, target definition, treatment plan development, and accurate treatment delivery. Appropriate QA procedures, including patient-specific QA procedures, are essential to ensure quality in an IMRT program and to assure patient safety.

American Society for Radiation Oncology (ASTRO) and American College of Radiology (ACR) practice guideline for the transperineal permanent brachytherapy of prostate cancer.

Transperineal permanent prostate brachytherapy is a safe and efficacious treatment option for patients with organ-confined prostate cancer. Careful adherence to established brachytherapy standards has been shown to improve the likelihood of procedural success and reduce the incidence of treatment-related morbidity. A collaborative effort of the American College of Radiology (ACR) and American Society for Therapeutic Radiation Oncology (ASTRO) has produced a practice guideline for permanent prostate brachytherapy. The guideline defines the qualifications and responsibilities of all the involved personnel, including the radiation oncologist, physicist and dosimetrist. Factors with respect to patient selection and appropriate use of supplemental treatment modalities such as external beam radiation and androgen suppression therapy are discussed. Logistics with respect to the brachytherapy implant procedure, the importance of dosimetric parameters, and attention to radiation safety procedures and documentation are presented. Adherence to these practice guidelines can be part of ensuring quality and safety in a successful prostate brachytherapy program.

The role of physicians and medical organizations in the development, analysis, and implementation of health care policy.

Health policy is developed in the United States through a complicated interplay of governmental and private agencies and businesses, physician organizations, and societies as well as a host of other private ventures. The end result is rarely precisely what any individual or group may desire as the consequences of any action are never entirely predictable. There are many pathways to influence policy development within this system, and many of these are influenced by physicians as individuals and through organized medical societies. Opportunities abound to constructively engage the system, and it is important that physicians operating within this system understand where and how they may influence policy development. Changes are made or considered on a daily basis that impact patient's access to care, implementation and access to technological and biological innovation, reporting requirements, insurance, physician's reimbursement, and so on. This article reviews the most important channels by which physician input is incorporated in the system. The role of specialty societies, general medical societies, Congress, and Centers for Medicare and Medicaid Services are reviewed. The role of other players will also be addressed to show the many routes by which policy may evolve. Much of the discussion revolves around reimbursement because reimbursement often determines the availability and use of procedures and technology for our patients.