Zachariah A. Allen

Risk Factors for the Development of Prostate Brachytherapy Related Urethral Strictures

PURPOSE We identified clinical, treatment and dosimetric parameters associated with the development of urethral strictures following permanent prostate brachytherapy. MATERIALS AND METHODS From April 1995 through April 2003, 1,186 consecutive patients underwent prostate brachytherapy for clinical stage T1b-T3a NxM0 (2002 American Joint Committee on Cancer) prostate cancer. The treatment plan included supplemental XRT in 625 patients (52.7%) and androgen deprivation therapy in 465 (39.2%). Median followup was 4.3 years. Multiple clinical, treatment and dosimetric parameters were evaluated in univariate and multivariate analyses to identify independent predictors for urethral stricture disease. RESULTS A total of 29 patients had brachytherapy related urethral strictures. All strictures involved the BM urethra with a 9-year actuarial risk of 3.6% and a median time to development of 2.4 years. The mean radiation dose to the BM urethra was significantly greater in patients with vs without stricture (p = 0.002). On multivariate analysis the BM urethral dose and supplemental XRT predicted urethral stricture. All except 3 patients were successfully treated with urethral dilation or internal optical urethrotomy. CONCLUSIONS Brachytherapy related urethral stricture disease correlates highly with the radiation dose to the BM urethra. Careful attention to brachytherapy preplanning and intraoperative execution along with the judicious use of supplemental XRT is essential to minimize the incidence of stricture disease.

Primary Causes of Death After Permanent Prostate Brachytherapy

PURPOSE To evaluate the primary causes of death in low-risk (low-risk), intermediate-risk (intermediate-risk), and high-risk (high-risk) patients undergoing permanent prostate brachytherapy with or without supplemental therapies. METHODS AND MATERIALS From April 1995 through November 2004, a total of 1,354 consecutive patients underwent prostate brachytherapy. All patients underwent brachytherapy >3 years before analysis. Of the patients, 532 (39.3%) received androgen deprivation therapy and 703 (51.9%) received supplemental radiation therapy. The median follow-up was 5.4 years. Multiple parameters were evaluated as predictors of cause-specific, biochemical progression-free, and overall survival. RESULTS The 10-year cause-specific survival was 97.0% (99.7%, 99.0%, and 90.1% for low-risk, intermediate-risk, and high-risk patients). Overall survival was 76.7% (82.5%, 78.3%, and 67.6% for low-, intermediate-, and high-risk patients, respectively). The cumulative death rate for cardiovascular disease was 11.5% (8.7%, 9.3%, and 19.8% for low-, intermediate-, and high-risk patients). The death rate from second malignancies (nonprostate cancer) was 7.2% and was not substantially different when stratified by risk group. Death from all other causes was 6.5% for the entire cohort but 1.3%, 5.0%, and 10.8% for low-, intermediate-, and high-risk patients. In multivariate analysis, death from prostate cancer was best predicted by Gleason score and risk group, whereas death from cardiovascular disease, nonprostate cancer, and all other causes were most closely related to patient age and tobacco use. CONCLUSIONS Although cardiovascular mortality was the predominant cause of death, prostate cancer was responsible for approximately 10% of all deaths. In particular, overall survival was poorest in the high-risk group. Although high-risk patients were most likely to die of prostate cancer, the divergence in overall survival between high-risk and lower-risk patients primarily resulted from an excess of cardiovascular deaths. Changes in lifestyle to improve cardiovascular health may improve overall survival in patients with clinically localized prostate cancer.

Severity categories of the International Prostate Symptom Score before, and urinary morbidity after, permanent prostate brachytherapy

To determine if the International Prostate Symptom Score (IPSS) before seed implantation, stratified into mild (0–7), moderate (8–19) and severe (>20) categories, predicts brachytherapy‐related morbidity in terms of IPSS resolution, catheter dependency and the need for surgical intervention after brachytherapy.

Late rectal function after prostate brachytherapy

PURPOSE Using a patient-administered quality of life instrument, to evaluate the effect of permanent prostate brachytherapy on late rectal function. METHODS AND MATERIALS One hundred eighty-nine prostate brachytherapy patients were mailed the Rectal Function Assessment Score (R-FAS), with a prestamped return envelope. The R-FAS consists of nine questions and a scoring range of 0-27, with higher scores indicative of poorer bowel function. One hundred eighty-seven (98.4%) surveys were returned. The median follow-up was 66.3 months (range 54-92 months). Clinical, treatment, and dosimetric parameters evaluated for bowel dysfunction included patient age, diabetes, hypertension, tobacco consumption, clinical T-stage, elapsed time since implant, prostate ultrasound volume, planning target volume, hormonal status, supplemental external beam radiation therapy (EBRT), isotope, average, median and maximum rectal doses, total implanted seed strength, values of the minimum dose received by 90% of the prostate gland (D(90)), and the percent prostate volume receiving 100%, 150%, and 200% of the minimum prescribed dose (V(100/150/200)). RESULTS The R-FAS score for the evaluated cohort was 3.92, which represented a slight improvement from the 1999 survey score of 4.15 (p = 0.29). Of the evaluated clinical, treatment, and dosimetric parameters, the number of preimplant bowel movements, a history of tobacco consumption, and the median rectal dose correlated with the R-FAS. Although lower rectal doses were noted with Pd-103, isotope did not predict for bowel function. Only 12% (23/187) of patients reported their bowel function to be worse after implantation. Patient perception of overall rectal quality of life was inversely related to the use of supplemental EBRT (p = 0.007). CONCLUSION Minor bowel changes are noted following prostate brachytherapy. The vast majority of patients did not report any deterioration in bowel function. In addition, the R-FAS continue to improve with time.

The Incidence of Transition Zone Prostate Cancer Diagnosed by Transperineal Template-guided Mapping Biopsy: Implications for Treatment Planning

OBJECTIVES To report the incidence of transition zone (TZ) cancer in patients undergoing transperineal template-guided mapping biopsy (TTMB) of the prostate gland. METHODS Five hundred thirty-nine consecutive patients underwent TTMB by means of an anatomic technique with sampling of 24 defined prostate regions. The position of each biopsy core was recorded in 3 dimensions. For every patient, the location of each positive biopsy core, the number of positive cores, the Gleason score, the percentage involvement of each core, and the presence/absence of perineural invasion was documented. RESULTS The median volumetric prostate volume was 56.0 cm(3) with an ellipsoid TZ volume of 20.1 cm(3). The median number of TTMB cores was 58 with a median of 11 TZ cores. Two hundred eighty-seven (53.2%) were diagnosed with prostate cancer. TZ cancer was detected in 130 (45.3%) of patients with prostate cancer but only 6 (4.6%) were confined to the TZ. Overall, 38.9% of TZ cores were positive for malignancy. Of the TZ cancers, 37 (28.5%), 64 (49.2%), and 29 (22.3%) were assigned Gleason scores 6, 7, and 8-10. Compared with a standard 12-core biopsy approach, the results of the TZ biopsy upgraded the Gleason score in 24.6% of patients. Only 4 cancers (3.1%) involving the TZ were classified as clinically insignificant. CONCLUSIONS Although only 4.6% of cancers were confined to the TZ, 45.3% of all prostate cancer patients had TZ involvement.

Brachytherapy in men aged £ 54 years with clinically localized prostate cancer

To report the biochemical progression‐free survival (BPFS) in hormone‐naive men aged ≤ 54 years who underwent brachytherapy with or without supplemental external beam radiation therapy (EBRT), as despite favourable biochemical control rates with brachytherapy, there remains a reluctance to recommend non‐extirpative approaches for young men with clinically localized prostate cancer.

Obesity Is Not Predictive of Overall Survival Following Permanent Prostate Brachytherapy

Purpose:To evaluate the impact of obesity on cause-specific (CSS), biochemical progression-free (bPFS), and overall survival (OS) following prostate brachytherapy. Materials and Methods:From April 1995 through March 2003, 1093 consecutive patients underwent brachytherapy for clinical T1b-T3a (2002 AJCC) prostate cancer. The median follow-up was 5.6 years. Evaluated body mass index (BMI) subgroups were <25 (n = 258), 25.0 to 29.9 (n = 547), 30.0 to 34.9 (n = 214), and ≥35 (n = 74) kg/m2, respectively. A total of 430 (39.9%) and 589 (53.9%) of the patients received androgen deprivation therapy or supplemental external beam radiation therapy, respectively. Multiple clinical, treatment, and dosimetric parameters were evaluated as predictors of CSS, bPFS, and OS. Results:The 11-year CSS, bPFS, and OS for the entire cohort were 97.5%, 95.6%, and 77.6%, respectively. BMI did not impact CSS or bPFS for any of the BMI cohorts. However, OS was statistically lower in patients with a BMI <25 kg/m2 (P = 0.014). A Cox linear regression analysis demonstrated that Gleason score was the best predictor of CSS while percent-positive biopsies, risk group, V100 and hypertension predicted for bPFS. Patient age and tobacco use were the strongest predictors of OS. A total of 128 patients have died with 108 (84.4%) of the deaths the result of cardiovascular/pulmonary disease (73) and second malignancies (35). To date, 12 patients have died of metastatic prostate cancer. Conclusion:Obesity did not impact CSS, bPFS, or OS in patients treated with permanent prostate brachytherapy. Cardiovascular or pulmonary disease and second malignancies substantially outweighed prostate cancer as competing causes of death.

Brachytherapy-related dysuria

To evaluate the incidence and temporal resolution of dysuria after permanent prostate brachytherapy, and to identify predictors of brachytherapy‐related dysuria.

Long-term rectal function after permanent prostate brachytherapy

Purpose:To evaluate the effect of prostate brachytherapy with or without supplemental therapies on long-term rectal function by means of a patient-administered quality-of-life instrument. Materials and Methods:As part of an ongoing prospective evaluation, 164 of an initial 209 patients who remain alive were mailed the Rectal Function Assessment Score (R-FAS) with a prestamped return envelope. R-FAS range from 0 to 27 with lower scores being indicative of better bowel function. Of the 162 eligible patients, 161 (99.4%) returned the survey. Median follow-up was 9.0 years (range 8.2–11.2 years). Clinical, treatment, and dosimetric parameters evaluated for bowel function included patient age, diabetes, hypertension, tobacco consumption, clinical T stage, elapsed time since brachytherapy, ultrasound volume, planning target volume, androgen deprivation therapy, supplemental external beam radiation, isotope, rectal dose, prostate D100/D150/D200, and prostate D90. Results:For the entire cohort, the current R-FAS was 3.59, which represented a nonstatistical improvement from prior surveys in 1999 (4.29) and 2002 (3.92) (P = 0.134). Only 16 patients (9.9%) reported bowel function to be worse after brachytherapy. Of the clinical, treatment, and dosimetric parameters evaluated, only the number of preimplant bowel movements, tobacco use, and diabetes correlated with R-FAS. Despite lower rectal doses with 103Pd, isotope did not predict for bowel function. Consistent with prior surveys, patient perception of overall rectal quality of life was inversely related to supplemental external beam radiation (P = 0.027). Conclusion:Prostate brachytherapy adversely affects bowel function. However, in most patients the changes are minimal and slowly resolve with time. Overall rectal quality of life is inversely related to supplemental external beam radiation.

Dosimetry of an extracapsular anulus following permanent prostate brachytherapy.

Purpose:Recent studies have suggested that extracapsular brachytherapy treatment margins correlate with biochemical control. It is likely that volumetric geographic dosimetric parameters will be more robust than selected radial measurements. Accordingly, we evaluated extracapsular volumetric dosimetric parameters in low-risk patients. Materials and Methods:A total of 263 low-risk prostate cancer patients randomized to Pd-103 versus I-125 were implanted with a brachytherapy target volume consisting of the prostate with a 5-mm periprostatic margin. The median follow-up was 4.2 years. All patients were implanted at least 3 years prior to analysis. Within 2 hours of implantation, an axial CT was obtained for postimplant dosimetry. A 5-mm three-dimensional periprostatic anulus was constructed around the prostate and evaluated in its entirety and in 90° segments. Prostate and anular dosimetric parameters consisted of V100/V150/V200 and D90. Biochemical progression-free survival (bPFS) was defined as a PSA ≤0.50 ng/mL after nadir. Results:The Pd-103 and I-125 arms were well-matched in terms of clinical, biochemical, and pathologic presentation. Six-year bPFS was 96.8% versus 99.2% for I-125 versus Pd-103 (P = 0.149). The most recent median posttreatment PSA was <0.04 ng/mL for both isotopes. No significant differences in postoperative anular doses were discerned between bPFS and failed patients. Conclusions:A postimplant 5-mm, three-dimensional periprostatic anulus provides substantial information regarding dosimetric coverage. However, with a median follow-up of 4.2 years, such volumetric and geographic parameters have not proven useful in predicting biochemical outcome in low-risk patients.