Faculty Bibliography

BACKGROUND:Despite revisions in 2005 and 2014, the Gleason prostate cancer (PCa) grading system still has major deficiencies. Combining of Gleason scores into a three-tiered grouping (6, 7, 8-10) is used most frequently for prognostic and therapeutic purposes. The lowest score, assigned 6, may be misunderstood as a cancer in the middle of the grading scale, and 3+4=7 and 4+3=7 are often considered the same prognostic group. OBJECTIVE:To verify that a new grading system accurately produces a smaller number of grades with the most significant prognostic differences, using multi-institutional and multimodal therapy data. DESIGN, SETTING, AND PARTICIPANTS/METHODS:Between 2005 and 2014, 20,845 consecutive men were treated by radical prostatectomy at five academic institutions; 5501 men were treated with radiotherapy at two academic institutions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS/METHODS:Outcome was based on biochemical recurrence (BCR). The log-rank test assessed univariable differences in BCR by Gleason score. Separate univariable and multivariable Cox proportional hazards used four possible categorizations of Gleason scores. RESULTS AND LIMITATIONS/CONCLUSIONS:In the surgery cohort, we found large differences in recurrence rates between both Gleason 3+4 versus 4+3 and Gleason 8 versus 9. The hazard ratios relative to Gleason score 6 were 1.9, 5.1, 8.0, and 11.7 for Gleason scores 3+4, 4+3, 8, and 9-10, respectively. These differences were attenuated in the radiotherapy cohort as a whole due to increased adjuvant or neoadjuvant hormones for patients with high-grade disease but were clearly seen in patients undergoing radiotherapy only. A five-grade group system had the highest prognostic discrimination for all cohorts on both univariable and multivariable analysis. The major limitation was the unavoidable use of prostate-specific antigen BCR as an end point as opposed to cancer-related death. CONCLUSIONS:The new PCa grading system has these benefits: more accurate grade stratification than current systems, simplified grading system of five grades, and lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa. PATIENT SUMMARY/RESULTS:We looked at outcomes for prostate cancer (PCa) treated with radical prostatectomy or radiation therapy and validated a new grading system with more accurate grade stratification than current systems, including a simplified grading system of five grades and a lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa.

OBJECTIVE:To characterize the impact of androgen-deprivation therapy (ADT) on the incidence of cardiovascular events (CE) in prostate cancer patients treated with radiotherapy (RT). MATERIALS AND METHODS/METHODS:There were 2211 patients with localized prostate cancer treated with RT from 1988 to 2008 at our institution. There were 991 patients (44.8%) who received ADT at the time of RT for a median of 6.1 months. Salvage ADT was initiated prior to CE in 365 men (16.5%) at a median of 5.5 years (range: 0.6 to 18.4 years) after RT and continued for a median of 4.3 years. A nomogram was constructed to predict the 10-year risk of CE "post-RT" (i.e., after RT). RESULTS:Patients receiving ADT at the time of RT exhibited significantly higher 10-year incidence of CE (19.6%, 95% CI 17.0%-22.6%) than those not receiving ADT (14.3%, 95% CI 12.2%-16.7%, P = .005). On multivariate analysis, both ADT at the time of RT (P = .007) and the time of salvage (P = .0004) were associated with increased CE risk, as were advanced age (P  =  .02), smoking (P  =  .0007), history of diabetes (P  =  .0007), and history of CE before RT (P  <  .0001). A nomogram using patient age, smoking status, history of pre-RT CE, history of diabetes, and ADT use at the time of RT predicted the rate of 10-year CE with a C-index of 0.81 (95% CI, 0.72-0.88). CONCLUSION/CONCLUSIONS:While ADT is often an essential part of prostate cancer treatment, patients should be counseled regarding increased risks of CE and prophylactic efforts should be considered to mitigate that risk.

PURPOSE/OBJECTIVE:We evaluated quality-of-life changes (QoL) in 907 patients treated with either radical prostatectomy (open or laparoscopic), real-time planned conformal brachytherapy, or high-dose intensity-modulated radiotherapy (IMRT) on a prospective IRB-approved longitudinal study. METHODS:Validated questionnaires given pretreatment (baseline) and at 3, 6, 9, 12, 15, 18, 24, 36, and 48 months addressed urinary function, urinary bother, bowel function, bowel bother, sexual function, and sexual bother. RESULTS:At 48 months, surgery had significantly higher urinary incontinence than others (both P<.001), but fewer urinary irritation/obstruction symptoms (all P<.001). Very low levels of bowel dysfunction were observed and only small subsets in each group showed rectal bleeding. Brachytherapy and IMRT showed better sexual function than surgery accounting for baseline function and other factors (delta 14.29 of 100, 95% CI, 8.57-20.01; and delta 10.5, 95% CI, 3.78-17.88). Sexual bother was similar. Four-year outcomes showed persistent urinary incontinence for surgery with more obstructive urinary symptoms for radiotherapy. Using modern radiotherapy delivery, bowel function deterioration is less-often observed. Sexual function was strongly affected in all groups yet significantly less for radiotherapy. CONCLUSIONS:Treatment selection should include patient preferences and balance predicted disease-free survival over a projected time vs potential impairment of QoL important for the patient.

PURPOSE:To report the long-term control and toxicity outcomes of patients with clinically localized prostate cancer, who underwent low-dose-rate prostate brachytherapy with magnetic resonance spectroscopic image (MRSI)-directed dose escalation to intraprostatic regions. METHODS AND MATERIALS:Forty-seven consecutive patients between May 2000 and December 2003 were analyzed retrospectively. Each patient underwent a preprocedural MRSI, and MRS-positive voxels suspicious for malignancy were identified. Intraoperative planning was used to determine the optimal seed distribution to deliver a standard prescription dose to the entire prostate, while escalating the dose to MRS-positive voxels to 150% of prescription. Each patient underwent transperineal implantation of radioactive seeds followed by same-day CT for postimplant dosimetry. RESULTS:The median prostate D90 (minimum dose received by 90% of the prostate) was 125.7% (interquartile range [IQR], 110.3-136.5%) of prescription. The median value for the MRS-positive mean dose was 229.9% (IQR, 200.0-251.9%). Median urethra D30 and rectal D30 values were 142.2% (137.5-168.2%) and 56.1% (40.1-63.4%), respectively. Median followup was 86.4 months (IQR, 49.8-117.6). The 10-year actuarial prostate-specific antigen relapse-free survival was 98% (95% confidence interval, 93-100%). Five patients (11%) experienced late Grade 3 urinary toxicity (e.g., urethral stricture), which improved after operative intervention. Four of these patients had dose-escalated voxels less than 1.0 cm from the urethra. CONCLUSIONS:Low-dose-rate brachytherapy with MRSI-directed dose escalation to suspicious intraprostatic regions exhibits excellent long-term biochemical control. Patients with dose-escalated voxels close to the urethra were at higher risk of late urinary stricture.