Primary Whole-gland Ablation for the Treatment of Clinically Localized Prostate Cancer: A Focal Therapy Society Best Practice Statement.

CONTEXT: Whole-gland ablation is a feasible and effective minimally invasive treatment for localized prostate cancer (PCa). Previous systematic reviews supported evidence for favorable functional outcomes, but oncological outcomes were inconclusive owing to limited follow-up. OBJECTIVE: To evaluate the real-world data on the mid- to long-term oncological and functional outcomes of whole-gland cryoablation and high-intensity focused ultrasound (HIFU) in patients with clinically localized PCa, and to provide expert recommendations and commentary on these findings. EVIDENCE ACQUISITION: We performed a systematic review of PubMed, Embase, and Cochrane Library publications through February 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. As endpoints, baseline clinical characteristics, and oncological and functional outcomes were assessed. To estimate the pooled prevalence of oncological, functional, and toxicity outcomes, and to quantify and explain the heterogeneity, random-effect meta-analyses and meta-regression analyses were performed. EVIDENCE SYNTHESIS: Twenty-nine studies were identified, including 14 on cryoablation and 15 on HIFU with a median follow-up of 72 mo. Most of the studies were retrospective (n = 23), with IDEAL (idea, development, exploration, assessment, and long-term study) stage 2b (n = 20) being most common. Biochemical recurrence-free survival, cancer-specific survival, overall survival, recurrence-free survival, and metastasis-free survival rates at 10 yr were 58%, 96%, 63%, 71-79%, and 84%, respectively. Erectile function was preserved in 37% of cases, and overall pad-free continence was achieved in 96% of cases, with a 1-yr rate of 97.4-98.8%. The rates of stricture, urinary retention, urinary tract infection, rectourethral fistula, and sepsis were observed to be 11%, 9.5%, 8%, 0.7%, and 0.8%, respectively. CONCLUSIONS: The mid- to long-term real-world data, and the safety profiles of cryoablation and HIFU are sound to support and be offered as primary treatment for appropriate patients with localized PCa. When compared with other existing treatment modalities for PCa, these ablative therapies provide nearly equivalent intermediate- to long-term oncological and toxicity outcomes, as well as excellent pad-free continence rates in the primary setting. This real-world clinical evidence provides long-term oncological and functional outcomes that enhance shared decision-making when balancing risks and expected outcomes that reflect patient preferences and values. PATIENT SUMMARY: Cryoablation and high-intensity focused ultrasound are minimally invasive treatments available to selectively treat localized prostate cancer, considering their nearly comparable intermediate- to long term cancer control and preservation of urinary continence to other radical treatments in the primary setting. However, a well-informed decision should be made based on one's values and preferences.

Evaluation and Active Treatment versus Active Surveillance of Localized Prostate Cancer in Renal Transplant Patients in the Era of Low and Very Low Risk Prostate Cancer.

PURPOSE: Current trends in renal transplantation, such as improved allograft/recipient survival and expanded organ transplantation eligibility criteria in older recipients, are concomitant with increasingly detected low risk prostate cancer in candidates for or recipients of renal transplantation. We reviewed the evidence regarding prostate cancer screening, diagnosis and management in renal transplant candidates and recipients. We focused on published reports of prostate cancer incidence and diagnosis in patients with end stage renal disease, pretransplant screening recommendations, and recommendations regarding waiting time between treatment and active wait listing after the prostate cancer diagnosis in renal transplant candidates. In addition, we examined the natural history of prostate cancer development after renal transplantation in the setting of standard immunosuppression. MATERIALS AND METHODS: We reviewed the English language literature using search terms including prostate cancer, end stage renal disease, renal transplantation, prostate cancer screening, prostate specific antigen, prostate cancer treatment and active surveillance in various combinations. RESULTS: Prostate cancer screening is still widely done in almost all patients with end stage renal disease before and after transplantation. Active treatment of any patients with prostate cancer and a 5-year waiting period before transplantation can negatively affect the collective pool of participants and the overall survival of patients on dialysis. Several groups have proposed a shorter waiting time to kidney transplantation in patients with low risk prostate cancer. CONCLUSIONS: There are no standardized guidelines for screening and management of prostate cancer before and after transplantation. In the era of low risk prostate cancer end stage renal disease is a significant competing mortality risk factor. The role of active surveillance in these complex cases has yet to be well investigated. Further studies and nomograms are urged to integrate risk stratified screening and treatment protocols before and after renal transplantation.

Salvage high-intensity focused ultrasound (HIFU) for locally recurrent prostate cancer after failed radiation therapy: Multi-institutional analysis of 418 patients.

OBJECTIVE: To report the oncological outcome of salvage high-intensity focused ultrasound (S-HIFU) for locally recurrent prostate cancer after external beam radiotherapy (EBRT) from a multicentre database. PATIENTS AND METHODS: This retrospective study comprises patients from nine centres with local recurrent disease after EBRT treated with S-HIFU from 1995 to 2009. The biochemical failure-free survival (bFFS) rate was based on the 'Phoenix' definition (PSA nadir + 2 ng/mL). Secondary endpoints included progression to metastasis and cancer-specific death. Kaplan-Meier analysis was performed examining overall (OS), cancer-specific (CSS) and metastasis-free survival (MFS). Adverse events and quality of life status are reported. RESULTS: In all, 418 patients with a mean (SD) follow-up of 3.5 (2.5) years were included. The mean (SD) age was 68.6 (5.8) years and the PSA level before S-HIFU was 6.8 (7.8) ng/mL. The median PSA nadir after S-HIFU was 0.19 ng/mL. The OS, CSS and MFS rates at 7 years were 72%, 82% and 81%, respectively. At 5 years the bFFS rate was 58%, 51% and 36% for pre-EBRT low-, intermediate- and high-risk patients, respectively. The 5-year bFFS rate was 67%, 42% and 22% for pre-S-HIFU PSA level ≤4, 4-10 and ≥10 ng/mL, respectively. Complication rates decreased after the introduction of specific post-RT parameters: incontinence (grade II or III) from 32% to 19% (P = 0.002); bladder outlet obstruction or stenosis from 30% to 15% (P = 0.003); recto-urethral fistula decreased from 9% to 0.6% (P < 0.001). Study limitations include being a retrospective analysis from a registry with no control group. CONCLUSION: S-HIFU for locally recurrent prostate cancer after failed EBRT is associated with 7-year CSS and MFS rates of >80% at a price of significant morbidity. S-HIFU should be initiated early following EBRT failure.

High-intensity focused ultrasound for focal therapy: reality or pitfall?

PURPOSE OF REVIEW: Progress in imaging, fusion software, and ablative modalities has fostered growth of the latest image-guided generation of high-intensity focused ultrasound (HIFU) for focal treatment of prostate cancer. Although early reports are encouraging, important questions remain regarding candidate selection, treatment, and outcomes. We review contemporary considerations for the use of HIFU for focal treatment of primary and radio-recurrent prostate cancer. RECENT FINDINGS: HIFU has been used to treat prostate cancer for over two decades. More recently, stage migration from screening and improvements in pelvic imaging and fusion technology has resulted in wider clinical application of focal HIFU as a first-line treatment for localized prostate cancer. Advanced imaging has also improved targeting for focal salvage therapy of radio-recurrent disease. Proponents point to the minimally invasive nature, limited morbidity profile, and ability to perform retreatments in the future. Critics emphasize positive post-treatment biopsies, nonuniform treatment protocols, and absence of long-term follow-up. Thus, a review of clinical considerations and recently published data is warranted. SUMMARY: Recent advances have strengthened support for the use of focal HIFU. Although HIFU has great potential, it must be applied judiciously, maintaining appropriate oncologic principles in the setting of standardized trials to determine its true clinical value.

Does the multidisciplinary approach improve oncological outcomes in men undergoing surgical treatment for prostate cancer?

OBJECTIVES: To determine whether oncological outcomes are improved in prostate cancer patients by using a multidisciplinary strategy as compared with a standard clinic paradigm, and whether time to treatment is delayed when using a multidisciplinary approach. METHODS: We retrospectively analyzed patients who were evaluated and pursued radical prostatectomy as primary treatment, by the same surgeons, in the prostate cancer multidisciplinary clinic (n = 194) and standard urology clinic (n = 741) at Duke University Medical Center from 2005 to 2009. Comparisons of baseline characteristics were examined using rank sum and χ(2) -tests. Differences in time to radical prostatectomy and oncological outcomes were evaluated using multivariate linear and Cox regression, respectively. RESULTS: A greater proportion of high-risk patients (D'Amico criteria) were evaluated at the multidisciplinary clinic compared with the urology clinic (23.2% vs 15.6%, P = 0.014). Mean-adjusted time from biopsy to radical prostatectomy was shorter for multidisciplinary clinic patients (85.6 vs 96.8 days, P = 0.006). After a median follow up of 21 months, no significant difference was found between the multidisciplinary clinic and urology clinic in the risk of biochemical recurrence after radical prostatectomy, whether controlling for clinical (hazard ratio 0.71, P = 0.249) or pathological variables (hazard ratio 0.75, P = 0.349). CONCLUSIONS: Despite higher-risk disease, men evaluated using the multidisciplinary approach have similar oncological outcomes compared with men undergoing standard evaluation. Furthermore, time to radical prostatectomy is not delayed by the multidisciplinary management of these patients.

Low central venous pressure versus acute normovolemic hemodilution versus conventional fluid management for reducing blood loss in radical retropubic prostatectomy: a randomized controlled trial.

OBJECTIVE: To compare acute normovolemic hemodilution versus low central venous pressure strategy versus conventional fluid management in reducing intraoperative estimated blood loss, hematocrit drop and need for blood transfusion in patients undergoing radical retropubic prostatectomy under general anesthesia. RESEARCH DESIGN AND METHODS: Patients undergoing radical retropubic prostatectomy under general anesthesia were randomized to conventional fluid management, acute normovolemic hemodilution or low central venous pressure (≤5 mmHg). Treatment effects on estimated blood loss and hematocrit change were tested in multivariable regression models accounting for surgeon, prostate size, and all two-way interactions. RESULTS: Ninety-two patients completed the study. Estimated blood loss (mean ± SD) was significantly lower with low central venous pressure (706 ± 362 ml) compared to acute normovolemic hemodilution (1103 ± 635 ml) and conventional (1051 ± 714 ml) groups (p = 0.0134). There was no difference between the groups in need for blood transfusion, or hematocrit drop from preoperative values. The multivariate model predicting estimated blood loss showed a significant effect of treatment (p = 0.0028) and prostate size (p = 0.0323), accounting for surgeon (p = 0.0013). In the model predicting hematocrit change, accounting for surgeon difference (p = 0.0037), the treatment effect depended on prostate size (p = 0.0007) with the slope of low central venous pressure differing from the other two groups. Hematocrit was predicted to drop more with increased prostate size in acute normovolemic hemodilution and conventional groups but not with low central venous pressure. KEY LIMITATIONS: Limitations include the inability to blind providers to group assignment, possible variability between providers in estimation of blood loss, and the relatively small sample size that was not powered to detect differences between the groups in need for blood transfusion. CONCLUSIONS: Maintaining low central venous pressure reduced estimated blood loss compared to conventional fluid management and acute normovolemic hemodilution in patients undergoing radical retropubic prostatectomy but there was no difference in allogeneic blood transfusion between the groups.

Phase 1 trial of neoadjuvant radiation therapy before prostatectomy for high-risk prostate cancer.

PURPOSE: To evaluate, in a phase 1 study, the safety of neoadjuvant whole-pelvis radiation therapy (RT) administered immediately before radical prostatectomy in men with high-risk prostate cancer. METHODS AND MATERIALS: Twelve men enrolled and completed a phase 1 single-institution trial between 2006 and 2010. Eligibility required a previously untreated diagnosis of localized but high-risk prostate cancer. Median follow-up was 46 months (range, 14-74 months). Radiation therapy was dose-escalated in a 3 × 3 design with dose levels of 39.6, 45, 50.4, and 54 Gy. The pelvic lymph nodes were treated up to 45 Gy with any additional dose given to the prostate and seminal vesicles. Radical prostatectomy was performed 4-8 weeks after RT completion. Primary outcome measure was intraoperative and postoperative day-30 morbidity. Secondary measures included late morbidity and oncologic outcomes. RESULTS: No intraoperative morbidity was seen. Chronic urinary grade 2+ toxicity occurred in 42%; 2 patients (17%) developed a symptomatic urethral stricture requiring dilation. Two-year actuarial biochemical recurrence-free survival was 67% (95% confidence interval 34%-86%). Patients with pT3 or positive surgical margin treated with neoadjuvant RT had a trend for improved biochemical recurrence-free survival compared with a historical cohort with similar adverse factors. CONCLUSIONS: Neoadjuvant RT is feasible with moderate urinary morbidity. However, oncologic outcomes do not seem to be substantially different from those with selective postoperative RT. If this multimodal approach is further evaluated in a phase 2 setting, 54 Gy should be used in combination with neoadjuvant androgen deprivation therapy to improve biochemical outcomes.

The number of high-risk factors and the risk of prostate cancer-specific mortality after brachytherapy: implications for treatment selection.

PURPOSE: To determine whether an increasing number of high-risk factors is associated with higher prostate cancer-specific mortality (PCSM) among men treated with brachytherapy (BT)-based treatment, and whether supplemental therapy has an impact on this risk. METHODS AND MATERIALS: We analyzed the cases of 2234 men with localized prostate cancer treated between 1991 and 2007 with low-dose rate BT monotherapy (n = 457) or BT with supplemental external-beam radiotherapy (EBRT, n = 229), androgen suppression therapy (AST, n = 424), or both (n = 1124). All men had at least one high-risk factor (prostate-specific antigen >20 ng/mL, biopsy Gleason score 8-10, or clinical stage ≥T2c). Competing-risks multivariable regressions were performed to determine whether the presence of at least two high-risk factors was associated with an increased risk of PCSM, with adjustment for age, comorbidity, and the type of supplemental treatment. RESULTS: The median follow-up time was 4.3 years. The number of men with at least two high-risk factors was highest in the group treated with BT, EBRT, and AST (21%), followed by BT plus EBRT or AST (13%), and BT alone (8%) (p(trend) < 0.001). The adjusted hazard ratio (AHR) for PCSM for those with at least two high-risk factors (as compared with one) was 4.8 (95% confidence interval [CI], 2.8-8.0; p < 0.001). The use of both supplemental EBRT and AST was associated with a decreased risk of PCSM (AHR 0.5; 95% CI, 0.2-0.9; p = 0.03) compared with BT alone. When the high-risk factors were analyzed separately, Gleason score 8-10 was most significantly associated with increased PCSM (AHR 6.2; 95% CI, 3.5-11.2; p < 0.001). CONCLUSIONS: Men with high-risk prostate adenocarcinoma treated with BT have decreased PCSM if they receive trimodailty therapy that includes EBRT and AST. This benefit is likely most important in men with multiple determinants of high risk.

Utilization trends at a multidisciplinary prostate cancer clinic: initial 5-year experience from the Duke Prostate Center.

PURPOSE: The multidisciplinary approach is becoming increasingly encouraged but little is known about the multidisciplinary experience compared to routine care. For patients with prostate cancer the goal is to provide evaluations by urologists, medical and radiation oncologists at a single visit. Although additional resources are required, this strategy may enhance the overall health care experience. We compared utilization determinants between a multidisciplinary and a urology prostate cancer clinic at Duke University Medical Center and identified factors associated with pursuing treatment at the university medical center for multidisciplinary clinic patients. MATERIALS AND METHODS: We retrospectively analyzed data on patients referred for primary prostate cancer treatment evaluation at Duke University Medical Center from 2005 to 2009. Comparisons between 701 multidisciplinary clinic and 1,318 urology prostate cancer clinic patients were examined with the rank sum and chi-square tests. Predictive factors for pursuing treatment at the university medical center were assessed using multivariate adjusted logistic regression. RESULTS: Compared to patients at the urology prostate cancer clinic those at the multidisciplinary clinic were more likely to be younger and white, have a higher income and travel a longer distance for evaluation. Of multidisciplinary clinic patients 58% pursued primary treatment at the university medical center. They were more likely to be younger, black and physician referred, have a lower income and reside closer to the medical center. Factors predictive of pursuing treatment at the medical center included high risk disease and physician referral. Factors predictive of not receiving care at the university medical center were income greater than $40,000 and a distance traveled of greater than 100 miles. CONCLUSIONS: A different patient demographic is using the multidisciplinary approach. However, when treatment is pursued at the institution providing multidisciplinary services, the patient demographic resembles that of the treating institution.

Factors predicting early and late phase decline of sexual health-related quality of life following radical prostatectomy.

INTRODUCTION: The association between early and late phase sexual health-related quality of life (HRQoL) following radical prostatectomy (RP) is unclear. Moreover, factors that predict either early or late sexual HRQoL decline have not been fully investigated. AIM: The aim of this study was to evaluate the correlation between early and late phase sexual HRQoL decline, and identify clinical parameters that predict substantial sexual HRQoL decline after surgery in the early phase (3 months) and late phase (20 months) following RP. METHODS: We analyzed data on 2,345 consecutive patients who underwent radical retropubic prostatectomy, radical perineal prostatectomy, or robotic-assisted laparoscopic prostatectomy between 2001 and 2009 from the Duke Prostate Center database. MAIN OUTCOME MEASURE: Sexual HRQoL was assessed using the Expanded Prostate Cancer Index Composite instrument at baseline, early and late phase after surgery. The Spearman rank test was used to calculate correlation coefficients between early and late phase sexual HRQoL decline. Logistic regression analysis was performed to identify factors associated with substantial sexual HRQoL decline during both phases. RESULTS: Of 406 men who met our criteria, 217 (53.5%) men had normal erectile function, whereas 189 (46.5%) men had erectile dysfunction at baseline. Declines of sexual HRQoL during early phase had a significant association with that of a decline during late phase (r = 0.48, P < 0.001). In logistic regression, older age at surgery (odds ratio [OR], 1.06; P = 0.007 and OR, 1.08; P = 0.001), African-American race (OR, 4.32; P = 0.001 and OR, 3.13; P = 0.017), and overall comorbidity (OR, 1.43; P = 0.072 and OR, 1.72; P = 0.010) were consistently associated with substantial decline of sexual HRQoL in both early and late phases. CONCLUSIONS: Sexual HRQoL at early and late phases after RP were strongly correlated. Additionally, several factors were identified to be a predictor for decline of sexual HRQoL. Our findings may be used to advise patients who possess aforementioned risk factors during both phases.

Salvage radiation in men after prostate-specific antigen failure and the risk of death.

BACKGROUND: A survival benefit has been observed with salvage radiation therapy (RT) for prostate-specific antigen (PSA) failure after radical prostatectomy (RP) in men with rapid rises in PSA doubling time (DT, < 6 months). Whether such a benefit exits in men with a protracted PSA rise in DT (≥ 6 months) is unclear and was examined in the current study. METHODS: Of 4036 men who underwent RP at Duke University between 1988 and 2008, 519 experienced a PSA failure, had complete data, and were the subjects of this study. Univariate and multivariate Cox regression analyses were performed to evaluate whether salvage RT in men with either a rapid (< 6 months) or a protracted (≥ 6 months) PSA DT was associated with the risk of all-cause mortality adjusting for age at the time of PSA failure, known prostate cancer prognostic factors, and cardiac comorbidity. RESULTS: After a median follow-up of 11.3 years after PSA failure, 195 men died. Salvage RT was associated with a significant reduction in all-cause mortality for men with either a PSA DT of < 6 months (adjusted hazard ratio [AHR], 0.53; P = .02) or a PSA DT of ≥ 6 months (AHR, 0.52; P = .003). In a subset of patients with comorbidity data at the time of PSA failure, salvage RT remained associated with a significant reduction in all-cause mortality for both men with a PSA DT of < 6 months (AHR, 0.35; P = .042) or a PSA DT of ≥ 6 months (AHR, 0.60; P = .04). CONCLUSIONS: Salvage RT for PSA DTs less than or in excess of 6 months is associated with a decreased risk in all-cause mortality.

Correlation of prostate-specific antigen nadir and biochemical failure after high-intensity focused ultrasound of localized prostate cancer based on the Stuttgart failure criteria - analysis from the @-Registry.

OBJECTIVE: •To determine if the prostate-specific antigen (PSA) nadir after high-intensity focused ultrasound (HIFU) can be used as a predictor of the biochemical disease-free survival rate (DFSR). PATIENTS AND METHODS: •Patient data were derived from the multicentre-based @-Registry, the largest registry to report outcomes in patients with localized prostate cancer after Ablatherm® HIFU. •PSA level was measured at 3-month intervals. Patients were stratified into four PSA nadir groups: group 1, ≤0.2 ng/mL; group 2, 0.21-0.5 ng/mL; group 3, 0.51-1 ng/mL; and group 4, >1 ng/mL. •Biochemical treatment failure was defined according to the Stuttgart definition (PSA nadir + 1.2 ng/mL) and the Phoenix definition (PSA nadir + 2 ng/mL). •Biopsy was performed at 3-6 months post-HIFU or if a PSA level was recorded that was considered clinically relevant. RESULTS: •The present study included 804 patients. Biochemical treatment success rates at 5 years according to the Stuttgart definition for the four PSA nadir sub-groups were as follows: 84, 64, 40 and 30% for groups 1-4, respectively. •The equivalent 5-year biochemical success rates using the Phoenix definition were 94, 74, 66 and 47%, respectively. •Significantly more patients had a negative biopsy in the lowest PSA nadir group than in the other sub-groups (91.6 vs 73.1%; P < 0.001). •The present study is limited by its retrospective nature and variations in clinical practice across participating centres. CONCLUSION: •This multicentre analysis confirms that PSA nadir after HIFU predicts biochemical DFSR in a statistically significant manner.

Prostate-specific antigen velocity based risk-adapted discontinuation of prostate cancer screening in elderly men.

OBJECTIVE: • To evaluate weather prostate-specific antigen (PSA) velocity could be used to stratify patients at risk of death from prostate cancer (PCa) and be useful in aiding decision making regarding PSA screening in elderly men, as previous studies have shown that PSA velocity can predict PCa risk. PATIENTS AND METHODS: • The cohort included 3,525 patients aged ≥ 75 years with two or more PSA tests before a diagnosis of PCa. Cox proportional hazard model was used to evaluate which variables at time of last PSA measurement were associated with death from PCa. • The rates of death from PCa after diagnosis in different PSA velocity groups were calculated. Kaplan-Meier and log rank test were used to assess the significant difference in death from PCa after diagnosis, stratified by PSA velocity cutoff. RESULTS: • On multivariate analysis, men with a PSA velocity of PSA velocity ≥ 0.45 ng/mL/year had a 4.8-fold higher risk of death from PCa as compared to men with a PSA velocity of < 0.45 ng/mL/year (p value = 0.013). After a median 6.5 (up to 16.9) years of follow-up from diagnosis, 1.4% of the men with a PSA velocity < 0.45 ng/mL/year had died of PCa as compared to 8.7% of those with a PSA velocity ≥ 0.45 ng/mL/year. • The cumulative rate of death from PCa after diagnosis, stratified by a PSA velocity of 0.45 ng/mL/year, was statistically different (log rank test, P < 0.001). CONCLUSION: • Men age ≥ 75 years old with a PSA velocity of <0.45 ng/mL/year are unlikely to die of PCa. It may be safe to discontinue PSA screening in these men.

Clinical predictors of renal mass pathological features.

OBJECTIVE: • To evaluate the influence of radiographic tumour size and other preoperative variables on the pathological characteristics of the lesion to determine the distribution of pathological features and assess preoperative risk factors for potentially aggressive versus probably indolent renal lesions. PATIENTS AND METHODS: • Retrospective review of records for 768 patients who underwent surgery for single, sporadic renal mass between 2000 and 2008 in a tertiary academic institution. • Demographic, radiographic and pathological variables were recorded and analysed with regression analyses for risk factors for potentially aggressive pathological features (malignant pathology, high Fuhrman grade, lymphovascular invasion and extracapsular extension). RESULTS: • Malignancy was pathologically confirmed in 628 (81.8%) specimens. • Radiographic size was significantly associated with malignancy (versus benign pathology; OR = 1.13, P= 0.001), high Fuhrman grade (OR = 1.21, P < 0.0001), vascular invasion (OR = 1.19, P < 0.0001) and extracapsular extension (OR = 1.23, P < 0.0001). • Age, symptomatic presentation, solid appearance and radiographic size were independent predictors of potentially aggressive disease, whereas for male gender (OR = 1.43, P= 0.062) a trend toward statistical significance was noted. CONCLUSIONS: • Age, male gender, radiographic size and appearance, as well as symptomatic presentation, are associated with an increased risk of malignant, potentially aggressive disease. • These factors should be considered when evaluating management options for a solitary enhancing renal mass.

Adjuvant versus salvage radiation therapy for prostate cancer and the risk of death.

OBJECTIVE: To investigate whether salvage radiation therapy (RT) for prostate-specific antigen (PSA) failure can provide the same result as adjuvant RT, which decreases the risk of all-cause mortality (ACM) for men with positive margins (R1), or extra-capsular or seminal vesicle extension (pT3). METHODS: We studied 1638 men at Duke University who underwent radical prostatectomy for unfavourable-risk prostate cancer and whose postoperative PSA was undetectable. Cox regression was used to evaluate whether salvage vs adjuvant RT in men with a rapid (<10 months) or slow (≥10 months) PSA doubling time (DT) was associated with the risk of ACM, adjusting for adverse features (pT3, R1, Gleason score 8-10), age, preoperative PSA level, comorbidity and hormonal therapy use. RESULTS: Despite fewer men with two or more adverse features (61 vs 82%; P=0.016), salvage for a rapid PSA DT vs adjuvant RT increased the risk of ACM [adjusted hazard ratio (AHR)=3.42; 95% confidence interval (CI)=1.27-9.20; P=0.015]. There was no difference (AHR=1.39; 95% CI=0.50-3.90; P=0.53) in the risk of ACM among men who received salvage for a slow PSA DT or adjuvant RT. Nearly all (90%) men with a slow PSA DT had Gleason score ≤7 and the majority (59%) had at most pT3 or R1 disease. CONCLUSION: Radiation therapy after PSA failure as compared with adjuvant RT was not associated with an increased risk of ACM in men with Gleason score ≤7 and pT3R0 or pT2R1 disease.

Predicting occult multifocality of renal cell carcinoma.

BACKGROUND: Multifocal renal cell carcinoma (RCC) has been reported in up to 25% of all radical nephrectomy specimens. Modern imaging tends to underestimate the rate of multifocality. Recognition of multifocality before treatment may guide physicians and patients to the type of intervention and tailor long-term follow-up. OBJECTIVE: Our aim was to develop and assess preoperative nomograms to predict occult multifocal RCC. DESIGN, SETTING, AND PARTICIPANTS: We evaluated 560 consecutive patients undergoing radical nephrectomy for clinically localized suspected sporadic RCC between 2000 and 2008 in a tertiary center. Clinically manifest multifocal lesions were excluded. Logistic regression models were used to assess the potential risk factors of occult multifocality with and without pathologic variables that may be available with preoperative biopsy. Nomograms were developed and assessed for diagnostic properties. INTERVENTIONS: All patients underwent radical nephrectomy. MEASUREMENTS: Assessments of risk factors for occult multifocal RCC were obtained using regression models and nomograms. RESULTS AND LIMITATIONS: The incidence of occult multifocality was 7.9%. Significantly associated predictors of multifocality were male gender, family history of malignancy other than RCC, radiographic size of the lesion, histologic subtype other than clear cell, and Fuhrman grade IV. The two designed nomograms had 0.75 and 0.82 concordance indices, respectively. CONCLUSIONS: Our data suggest that occult multifocal RCC is more frequently associated with small (2-4 cm) renal lesions. Male gender, family history of kidney cancer, histologic subtype, and grade are strongly associated with an increased risk of occult multifocal RCC. The developed nomograms had good predictive accuracy that was enhanced when combined with pathologic variables.

Impact of postoperative prostate-specific antigen disease recurrence and the use of salvage therapy on the risk of death.

BACKGROUND: This report evaluated whether biochemical recurrence (BCR) as a time-dependent covariate (t) after radical prostatectomy (RP) for prostate cancer was associated with the risk of death and whether salvage therapy with radiotherapy (RT) and/or hormonal therapy (HT) can lessen this risk METHODS: This was a retrospective cohort study of 3071 men who underwent RP at Duke University between 1988 and 2008 and had complete follow-up data. A Cox regression multivariable analysis was used to determine whether BCR (t) was associated with the risk of death in men after adjusting for age, prostatectomy findings, and the use of salvage RT and/or HT. RESULTS: After a median follow-up of 7.4 years, 546 (17.8%) men experienced BCR and 454 (14.8%) died. The median follow-up after prostate-specific antigen (PSA) failure was 11.2 years (interquartile range, 5.8-16.0 years). BCR (t) was associated with an increased risk of death (adjusted hazards ratio [AHR], 1.03; 95% confidence interval [95% CI], 1.004-1.06 [P = .025]). In men who experienced BCR, a PSA doubling time <6 months was associated with an increased risk of death (AHR, 1.55; 95% CI, 1.15-2.1 [P = .004]); whereas a decrease in the risk of death was observed in men who received RT (AHR, 0.58; 95% CI, 0.40-0.58 [P = .002]) or HT (AHR, 0.56; 95% CI, 0.37-0.84 [P = .005]) after BCR. CONCLUSIONS: The occurrence of BCR was found to increase the risk of death in men undergoing RP for prostate cancer, and this risk appeared to increase as the time to BCR shortened. However, the addition of RT and/or HT in men with BCR significantly lowered this risk.

Tumor percent involvement predicts prostate specific antigen recurrence after radical prostatectomy only in men with smaller prostate.

PURPOSE: We determined the predictive power of tumor percent involvement on prostate specific antigen recurrence in patients when stratified by prostate weight. MATERIALS AND METHODS: Data on 3,057 patients who underwent radical prostatectomy between 1988 and 2008 was retrieved from our institutional prostate cancer database. Patients with data on tumor percent involvement, prostate volume and prostate specific antigen recurrence were included in analysis. Patients were divided into 3 groups based on prostate volume less than 35, 35 to 45 and greater than 45 cc. The variables tumor percent involvement, age at surgery, race, prostate specific antigen, pathological Gleason score, positive surgical margins, extraprostatic extension, seminal vesicle invasion and surgery year were analyzed using the chi-square and Mann-Whitney tests to determine individual effects on prostate specific antigen recurrence. Tumor percent involvement and prostate specific antigen were evaluated as continuous variables. Significant variables on univariate analysis were included in multivariate Cox regression analysis to compare their effects on prostate specific antigen recurrence. RESULTS: Tumor percent involvement significantly predicted prostate specific antigen recurrence in men with a small prostate (p = 0.006) but not in those with a prostate of greater than 35 cc. Black race was a marginally significant predictor of prostate specific antigen recurrence in men with a medium prostate (p = 0.055). Age at surgery was a predictor of prostate specific antigen recurrence in men with a larger prostate (p = 0.003). Prostate specific antigen, positive surgical margins, seminal vesicle invasion and pathological Gleason score 7 or greater predicted prostate specific antigen recurrence in men with all prostate sizes. CONCLUSIONS: In men with a prostate of less than 35 cc tumor percent involvement is an important variable when assessing the risk of prostate specific antigen recurrence. Tumor percent involvement and prostate volume should be considered when counseling patients and determining who may benefit from heightened surveillance after radical prostatectomy.