Androgen deprivation-induced changes in prostate anatomy predict urinary morbidity after permanent interstitial brachytherapy.

PURPOSE: To evaluate the cytoreductive consequences of neoadjuvant androgen deprivation therapy on International Prostate Symptom Score (IPSS) normalization, catheter dependency, and the need for surgical intervention secondary to bladder outlet obstruction after permanent interstitial brachytherapy. METHODS AND MATERIALS: A total of 116 patients (median follow-up, 30 months) with preandrogen and postandrogen deprivation therapy ultrasound studies and no history of preimplant transurethral resection of the prostate were evaluated. Androgen deprivation-induced changes in prostate volume, transition zone (TZ) volume, and urethral location were correlated with IPSS resolution, catheter dependency, and the need for postimplant surgical intervention. Prostate gland and TZ dimensions and volumes were measured by prolate ellipsoid calculation from the static ultrasound images. The urethral location was determined by identification of a urinary catheter. Additional clinical, treatment, and dosimetric parameters evaluated included patient age, pretreatment prostate-specific antigen, Gleason score, clinical T stage, preimplant IPSS, pre- and postandrogen deprivation ultrasound studies, treatment planning volume, supplemental external beam RT, isotope, total implant activity, Day 0 maximal dose received by 90% of the prostate gland, Day 0 percentage of prostate volume receiving 100%, 150%, and 200% of the prescribed minimal peripheral dose, and urethral dose. RESULTS: For hormonally manipulated patients, the prostate volume at implantation did not have a statistical influence on the percentage of patients returning to IPSS baseline, the time for IPSS normalization, the incidence of catheter dependency, the catheter-dependency time, or the need for postimplant surgical intervention. However, when compared with the hormone-naive cohort, hormonally manipulated patients were more likely to undergo postimplant surgical intervention (5.2% vs. 0.3%, p = 0.001). Greater androgen deprivation-induced reductions in prostate and TZ volumes, along with movement of the urethra closer to the posterior border of the prostate gland, resulted in a decreased incidence of postimplant urinary morbidity. Using Cox regression analysis, the time to IPSS resolution was best predicted by the percentage of TZ volume reduction. Stepwise linear regression analysis demonstrated that the catheter-dependency time was best predicted by the prehormonal therapy prostate volume, posthormonal therapy TZ volume, and the change in the urethral position; prolonged catheter dependency by the percentage of TZ volume reduction, prehormonal therapy TZ index, and the change in the urethral position; and the need for postimplant surgical intervention by the posthormonal therapy TZ index and the change in the urethral location. CONCLUSION: After neoadjuvant androgen deprivation therapy for volume reduction, some brachytherapy-related urinary morbidity parameters are highly related to the preandrogen deprivation prostate volume, variants in the TZ volume, and changes in the urethral location.

Prostate-specific antigen (PSA) velocity and benign prostate hypertrophy predict for PSA spikes following prostate brachytherapy.

PURPOSE: To evaluate if variants of serum PSA or benign prostatic hypertrophy correlate with the development of a PSA spike following permanent prostate brachytherapy. METHODS AND MATERIALS: Two-hundred-eighteen hormone-naïve patients with clinical T1b-T3a (1997 AJCC) prostate cancer who were treated with brachytherapy between August 1995 and November 1999, with or without supplemental external beam radiation therapy, and who remained free of biochemical failure were analyzed. The median follow-up was 46 months. A PSA spike was defined as a rise > or =0.2 ng/mL followed by a durable decline. Biochemical disease-free survival was defined by the ASTRO Consensus Definition with the additional constraint that the most recent PSA be < or =1.0 ng/mL. In addition, none of the patients possessed equivocal biochemical results (1 or 2 consecutive PSA rises or a declining PSA >1.0 ng/mL). In addition to previously reported clinical, treatment, and dosimetric parameters evaluated for spike, PSA density, transition zone (TZ) PSA density, percent free PSA, PSA velocity, PSA doubling time, TZ volume, and transition zone index (TZI) were included. The PSA kinetics of 18 hormone naïve patients who were implanted during the same time period and subsequently failed were also evaluated. RESULTS: Fifty-two (23.9%) developed a PSA spike. Of the demographic and preimplant clinical parameters, patient age, TZ volume, TZI, TZ PSA density, and 125I were statistically significant predictors for a PSA spike. Of the postimplant parameters, V200, follow-up, first postimplant PSA, and most recent PSA predicted for a PSA spike. In multivariate Cox regression analysis, PSA nadir, TZI, follow-up, age, months to PSA nadir and preimplant PSA velocity were significant predictors for spike. However, when variables only determinable after a PSA spike were included in the multivariate analysis, TZI, age, PSA velocity, and first postimplant PSA were predictors for a spike. Using categorical cutpoints of TZI >0.25, age at implant <62 years, and first postimplant PSA >1.0 ng/mL in the regression analysis, a positive likelihood ratio for a PSA spike of >1.8 was noted for each variable. Patients with PSA progression displayed significantly different PSA kinetics than those with a spike. CONCLUSIONS: In multivariate analysis, PSA nadir, TZI, patient age, months to PSA nadir, follow-up, and preimplant PSA velocity were predictive of a PSA spike. However, when only variables identifiable prior to a spike were evaluated, TZI, patient age, preimplant PSA velocity, and first postimplant PSA were the strongest predictors for a PSA spike.

The impact of prostate volume and neoadjuvant androgen-deprivation therapy on urinary function following prostate brachytherapy.

PURPOSE: The purpose of this article is to evaluate the impact of prostate size and the magnitude of cytoreduction after neoadjuvant androgen-deprivation therapy (ADT) on catheter dependency, urinary symptomatology, and need for postbrachytherapy surgical intervention. MATERIALS AND METHODS: From February 1998 to August 2002, 186 consecutive patients under went monotherapeutic brachytherapy (no supplemental external-beam radiotherapy or ADT), and 101 consecutive patients received < or = 6 months of ADT (a luteinizing hormone-releasing hormone agonist and an anti-androgen) in conjunction with brachytherapy without supplemental external-beam radiotherapy for clinical Tlc-T2b (2002 American Joint Committee on Cancer) prostate cancer. ADT was initiated approximately 3 months before brachytherapy. The median follow-up was 38.6 months. An alpha-blocker was initiated before implantation and continued at least until the International Prostate Symptom Score (IPSS) returned to baseline levels. Evaluated parameters included patient age, pretreatment prostate-specific antigen, Gleason score, clinical T stage, preimplantation IPSS, ultrasound volume, hormonal status, isotope, D(90), V(100/150/200), and urethral dose (average and maximum). RESULTS: Patients receiving neoadjuvant ADT were statistically older, presented with higher preimplantation IPSS scores, and larger prostate volumes. Patients receiving ADT were likelier to require a urinary catheter for the first 3 days after implantation; however, by day 4, no statistical difference in catheter dependency could be discerned between the two cohorts. Hormonal status did not predict for postbrachytherapy surgical intervention. IPSS returned to baseline at a mean of 1.8 and 1.7 months in hormone-naive and ADT patients, respectively. In multivariate Cox regression analysis, the preimplantation IPSS and the maximum postimplantation IPSS predicted for IPSS normalization overall and in both cohorts. Ultrasound prostate volume did not predict for IPSS normalization, catheter dependency, or need for postimplantation surgical intervention. CONCLUSION: Although patients receiving ADT were likelier to require a urinary catheter for the first three days after implantation, hormonal manipulation did not affect IPSS normalization, prolonged catheter dependency, or need for postbrachytherapy surgical intervention in these patients treated with brachytherapy without supplemental external-beam radiotherapy.