Primary Androgen Deprivation Research Articles

Primary androgen deprivation (PAD) followed by active surveillance for newly diagnosed prostate cancer (PC).

244 Background: Men undergoing local therapy (LT) with radiation or surgery incur substantial risk of permanent sexual, urinary and rectal toxicity. Active surveillance is only recommended for men with Low-Risk PC who have < 34% biopsy cores positive. Studies of PAD as an alternative to LT are sparse. Methods: Retrospective analysis of 102 men with localized PC administered 12 months of an LHRH agonist and antiandrogen (PAD) followed by immediate biopsy (BX1). Outcome assessed: The incidence of implementing further treatment with either LT or androgen deprivation (AD) if there was subsequent progression on active surveillance (PAS) or if BX1 was positive. Post PAD monitoring included quarterly PSA testing, follow-up biopsy and imaging with color doppler ultrasound and endorectal MRI. Participants were screened for heart disease and osteoporosis and monitored for changes in body weight, BP, liver enzymes, anemia, blood sugar and cholesterol. All received empiric bisphosphonates and 5-alpha reductase inhibitors and were instructed to eat a low fat diet and perform resistance exercise. Results: Patient characteristics: D’Amico risk category (DRC) Low: n=22; Intermediate: n=30; High: n= 50. Baseline factors assessed as potential predictors of PAS: Age, PSA, PSA velocity, PSA nadir, Gleason, % core biopsies, stage, prostate volume, DRC. Baseline medians for the 102 men: Age 67.3, PSA 7.8, Gleason 3+4, Cores > 50%, stage T1c, prostate volume 45cc. 55 men had PAS and required LT and/or AD over a median of 7.3 years follow up. Type of treatment administered after PAS by DRC: Low: AD 1, LT 3. Intermediate: AD 5, LT 10. High: AD 15, LT 21. Two men developed clinical progression. There were no PC deaths. Four men died of other causes: lung CA, melanoma, emphysema and MI. Only DRC (p<0.01) and PSA nadir (p<0.04) predicted PAS (3 men had PSA nadir > 0.1 and all were positive at BX1). Conclusions: PAD frequently induces durable remissions in men with Low and Intermediate risk PC despite a high prevalence of > 50% core biopsies positive at baseline in this population. 38% of the 55 men with PAD elected additional AD rather than undergoing LT suggesting that for some men enduring the toxicity profile of AD was preferable to the perceived risks of LT.

Preclinical Characterization of a Novel Diphenyl Benzamide Selective ERα Agonist for Hormone Therapy in Prostate Cancer

Androgen deprivation therapy (ADT) is the mainstay of treatment for advanced prostate cancer. ADT improves overall and disease-free survival rates, but long-term therapy is associated with severe side effects of androgen and estrogen depletion including hot flashes, weight gain, depression, and osteoporosis. Effective hormone reduction can be achieved without estrogen deficiency-related side effects by using therapy with estrogenic compounds. However, cardiovascular complications induced by estrogens coupled with the availability of LHRH agonists led to discontinuation of estrogen use for primary androgen deprivation therapy in the 1980s. New treatments for prostate cancer that improve patient outcomes without the serious estrogen deficiency-related toxicities associated with ADT using LHRH analogs are needed. Herein we describe a novel nonsteroidal selective estrogen receptor-α agonist designed for first-line therapy of advanced prostate cancer that in animal models induces medical castration and minimizes many of the estrogen deficiency-related side effects of ADT. The present studies show that orally administered GTx-758 reversibly suppressed testosterone to castrate levels and subsequently reduced prostate volume and circulating prostate-specific antigen in relevant preclinical models without inducing hot flashes, bone loss, thrombophilia, hypercoagulation, or increasing fat mass.

Androgen Deprivation Therapy as Primary Treatment for Prostate Cancer

Hormonal therapy has been the mainstay of treatment for advanced prostate cancer for over 70 yr. The timing and extent of androgen ablative therapy for earlier stage disease remains controversial. In addition, recent studies demonstrate that so-called "castration-resistant" tumors are still dependent on androgen receptor signaling. A 66-yr-old man presented with clinical stage T1C N+ M0 prostate cancer and received primary androgen deprivation therapy. Over the course of the next 17 yr, he was treated with various forms of androgen deprivation therapy, including two newer agents, abiraterone acetate and MDV 3100. A review of the literature was conducted to identify indications, controversies, and new developments regarding hormonal therapy for prostate cancer. Androgen deprivation therapy remains the treatment of choice for metastatic prostate cancer; however, it is not without its adverse effects, and most men with advanced disease eventually develop castration resistance. Newer compounds that more specifically and effectively target androgen and androgen receptor signaling in prostate cancer cells may provide more long-lasting remissions in advanced disease.

Radiation Therapy for Prostate Cancer Increases the Risk of Subsequent Rectal Cancer

To assess whether radiation therapy for prostate cancer (PCa) increases the risk of metachronous rectal cancer (RCa) and compare outcomes of RCa after radiation therapy and surgery. The Israel Cancer Registry was queried to identify patients with PCa and RCa diagnosed between 1982 and 2005. The age adjusted standardized incidence ratio (SIR) of RCa was defined as the ratio between the observed and expected (calculated) RCa cases and compared among the following: overall Israeli male population, patients with PCa treated with radiation therapy, patients with PCa treated surgically. The medical records of men diagnosed with RCa were reviewed and clinical characteristics retrieved. Of 29,593 men diagnosed with PCa, 2163 were treated with radiation therapy, 6762 were treated surgically and 20,068 patients were treated with either primary androgen deprivation therapy or offered watchful waiting. Of the entire study cohort, 194 (0.65%) patients were diagnosed with subsequent RCa. Compared to the overall male population and stratified by treatment modality, the risk of developing RCa after radiation therapy was significantly increased (SIR = 1.81, 95% CI 1.2-2.5), whereas it was not increased in those managed by surgery (SIR = 1.22, 95% CI 0.85-1.65). RCa after radiation therapy was diagnosed at a more advanced stage, translating into inferior disease specific survival. Compared to men diagnosed with PCa managed by surgery, we observed an increased risk of RCa in patients treated with radiation therapy. Further studies are needed to validate these findings and assess whether routine colonoscopic surveillance is warranted after pelvic radiation.

Cardiovascular comorbidity and treatment regret in men with recurrent prostate cancer

Study Type - Therapy (case series). Level of Evidence 4. What's known on the subject? and What does the study add? Treatment regret can have an adverse impact on a patient's overall outlook and has been associated with a poorer global quality of life. Understanding predictors of regret can help clinicians better counsel patients about their treatments so that later regret can be avoided. In previous studies, regret has been associated with lesser educational attainment, non-White race, greater post-treatment declines in sexual function and systemic symptoms. The present study found that, among men with recurrent prostate cancer, those with cardiovascular comorbidity were >50% more likely to regret their treatment choice than men without cardiovascular comorbidity. This study highlights the growing importance of considering comorbidity when counselling patients about prostate cancer treatment options, and provides a rationale for men with cardiovascular comorbidity to give additional consideration to active surveillance for their newly diagnosed prostate cancer. • To determine whether cardiovascular comorbidity is associated with increased treatment regret among men with recurrent prostate cancer. • The study cohort comprised 795 men in the Comprehensive, Observational, Multicenter, Prostate Adenocarcinoma (COMPARE) registry who experienced biochemical recurrence at a median (interquartile range) of 5.5 (2.8-9.1) years after prostatectomy (n= 410), external beam radiation therapy (n= 237), brachytherapy (n= 124) or primary androgen deprivation therapy (n= 24). • Multivariable logistic regression analysis was used to determine whether cardiovascular comorbidity was associated with treatment regret. • Cardiovascular comorbidity, which included myocardial infarction, congestive heart failure, angina, diabetes, stroke or circulation problems, was defined using a validated two-question screening process after adjusting for sociodemographic and treatment factors and post-treatment bladder and bowel toxicity. • Of 795 men, 14.8% reported regret. • Men with cardiovascular comorbidity were more likely to experience post-therapy bowel toxicity (P= 0.022). • In the adjusted multivariable model, the factors associated with increased treatment regret were: cardiovascular comorbidity (adjusted odds ratio [AOR]= 1.52 [95% CI:1.00-2.31], P= 0.048); younger age (AOR: 0.97 [95% CI 0.94-0.99] per year increase in age, P= 0.019); and bowel toxicity after treatment (AOR 1.58 [95% CI 1.03-2.43], P= 0.038). • Among men with recurrent prostate cancer, those with cardiovascular comorbidity were >50% more likely to experience treatment regret than men without cardiovascular comorbidity. • These data provide a rationale for men with cardiovascular comorbidity to give additional consideration to active surveillance for their newly diagnosed prostate cancer.

Primary Intermittent Androgen Deprivation As Initial Therapy for Men with Newly Diagnosed Prostate Cancer

Background The purpose of this study was to describe the long-term incidence of cancer progression and mortality in men with localized prostate cancer treated with primary androgen deprivation (AD). Methods A retrospective chart review, from a medical oncology practice specializing in prostate cancer, was conducted of 73 men eligible for surgery or radiation treated with induction AD. Entry criteria consisted of a minimum of 9 months of induction AD, treatment initiation before 1999, clinical stage < T3, and outcome defined as the incidence of delayed local therapy, cancer progression, cancer mortality, and mortality from other causes. Results Median follow-up was 12 years. Fifteen men were at low risk, 38 were at intermediate risk, and 20 were at high risk. Three men (4%) experienced metastatic disease and died of prostate cancer after 3.5, 7.7, and 11 years, respectively. Two men were in the intermediate-risk category and 1 was high risk. Nineteen men (26%) died of non–prostate cancer causes. None had metastatic disease at the time of death. Of the remaining 51 survivors, none has experienced bone metastasis. Twenty-one men (29%) required no further therapy after the first induction course of AD. Twenty-four men (33%) maintained a prostate-specific antigen (PSA) level < 5.0 ng/mL with 2 to 5 cycles of intermittent AD. Twenty-eight men (38%) underwent delayed local therapy after a median of 5.5 years. Median follow-up after local therapy was 6.2 years. Three of these men experienced subsequent rising PSA levels but none has progressed to bone metastasis. Sixteen of 20 men (80%) in the high-risk category but only 12 of 53 men (23%) in the low- and intermediate-risk categories had delayed local therapy. Conclusions Primary intermittent AD is feasible for men with localized prostate cancer. Men who are younger and men with high-risk disease undergo delayed local therapy more frequently.

Secondary Hormonal Therapy in Men With Castration-Resistant Prostate Cancer

Background Androgen receptor (AR) signaling remains important in castration-resistant prostate cancer (CRPC) and sequential responses to hormonal therapies are observed. Little is known about the factors associated with responsiveness to secondary hormone therapy (HT). Methods We retrospectively identified patients with CRPC who were treated with secondary HT. Patient characteristics and types and duration of secondary HT were analyzed. Selected clinical characteristics and their association with duration of secondary HT were evaluated. Results Of 436 eligible patients, 321 (74%) and 87 (20%) received at least two or four secondary HT regimens, respectively. Median duration of time on primary androgen deprivation therapy alone (ADT) and secondary HT were 24.0 months (range, 1.5 to 171.8 months) and 30.3 months (range, 0.6 to 156.1+ months), respectively. Patients who received primary ADT ≥ 24 months received secondary HT for a median duration of 40.0 months, whereas men who received ADT < 24 months had a median duration of 18.4 months on secondary HT ( P < .0001). Metastatic disease at secondary HT initiation was associated with a shorter time on secondary HT ( P = .0001). Patients who received the first secondary HT for ≥ 6 months were more likely to have a longer duration on subsequent secondary HT compared with the men who received the first secondary HT < 6 months ( P = .0001). Conclusions Treatment durations of secondary HT are variable. Longer duration of primary ADT was associated with longer duration of secondary HT. These results imply that AR signaling remains an important therapeutic target in CRPC.

UP-02.154 Duration of Androgen Deprivation Therapy with Maximum Androgen Blockade for Localized Prostate Cancer

Primary androgen deprivation therapy (ADT) is a treatment option not only for advanced but for also localized prostate cancer. It is of importance to define the optimal duration of primary ADT, which not only can yield long-term cancer control or cure, but can also reduce adverse events and cost and maintain QOL. To date, however, few studies have addressed this issue, and it remains inconclusive. The present study explored the appropriate duration of primary ADT for localized prostate cancer by pathologically reviewing cancer status in radical prostatectomy specimens after neoadjuvant ADT with maximum androgen blockade (MAB).

MP-16.03 Nadir Prostate Specific Antigen (PSA) Level and Time to PSA Nadir Following Primary Androgen Deprivation Therapy Are the Early Survival Predictors for Prostate Cancer Patients with Bone Metastasis

MP-16.03 Nadir Prostate Specific Antigen (PSA) Level and Time to PSA Nadir Following Primary Androgen Deprivation Therapy Are the Early Survival Predictors for Prostate Cancer Patients with Bone Metastasis

Aktuelle Therapie des fortgeschrittenen Prostatakarzinoms

Despite the broad use of PSA-testing in western medicine, still an estimated 1/3 of carcinomas of the prostate (PC) are diagnosed in a locally advanced or metastatic stage. In the current treatment-algorithm for locally advanced PC, radical prostatectomy, external beam radiation therapy (with and without hormonal therapy) and primary androgen deprivation are available. In fact, in a majority of patients treatment of this tumor stage will be a multimodal approach, which has to be discussed individually. For metastatic PC hormonal deprivation therapy is still the gold standard. Beside LHRH-agonists, surgical castration and complete androgen deprivation today LHRH-antagonists represent the different therapeutic options in this tumor stage. Effects on natural course of this disease have to be balanced to the side effects of long-term therapy. Castration-resistant PC is not the object of this overview even though there are a variety of new medical interventions emerging for the treatment of this stage of PC.

Black Men Have Lower Rates Than White Men of Biochemical Failure with Primary Androgen-Deprivation Therapy

Black men have a higher incidence of advanced stage at diagnosis and mortality from prostate cancer than do men in other racial groups. Given that androgen-deprivation therapy (ADT) is one of the mainstays of treatment for advanced prostate cancer, we investigated the development of biochemical failure, or recurrence of elevated prostate-specific antigen (PSA) levels, among different races in men receiving ADT. Patients with prostate cancer who received ADT in the Kaiser Permanente Southern California Cancer Registry between January 2003 and December 2006 were eligible for inclusion in our study. Patients who had prior treatment for their cancer with surgery or radiation were excluded. Treatment failure was defined as an increase in PSA of >2 ng/mL from PSA nadir, with no subsequent decrease in PSA. We compared the biochemical failure rate in white patients to those in black, Hispanic, and Asian/other patients. The Cox proportional hazards regression model was used to estimate hazards ratios. Our study population consisted of 681 patients: 416 (61%) were white; 107 (16%) were black; 107 (16%) were Hispanic; and 51 (7%) were Asian or another race. After we controlled for all demographic variables and for variables related to prostate cancer, blacks were the only group with a lower risk of treatment failure compared with whites. The hazard ratios for treatment failure were as follows: black versus white, 0.66 (p = 0.03); Hispanic versus white, 1.00 (p = 0.8); Asian/other race versus white, 1.5 (p = 0.1). In this multivariate analysis, pretreatment PSA level and cancer stage were the only other variables associated with a higher risk of treatment failure. Among patients receiving ADT as primary monotherapy for prostate cancer, blacks may have a lower rate of biochemical failure compared with whites. Although the etiology of this finding is unclear, it suggests the possibility that prostate cancer in black men may be more androgen sensitive than it is in white men.

Serum Early Prostate Cancer Antigen (EPCA) Level and Its Association with Disease Progression in Prostate Cancer in a Chinese Population

BackgroundEarly prostate cancer antigen (EPCA) has been shown a prostate cancer (PCa)-associated nuclear matrix protein, however, its serum status and prognostic power in PCa are unknown. The goals of this study are to measure serum EPCA levels in a cohort of patients with PCa prior to the treatment, and to evaluate the clinical value of serum EPCA.MethodsPretreatment serum EPCA levels were determined with an ELISA in 77 patients with clinically localized PCa who underwent radical prostatectomy and 51 patients with locally advanced or metastatic disease who received primary androgen deprivation therapy, and were correlated with clinicopathological variables and disease progression. Serum EPCA levels were also examined in 40 healthy controls.ResultsPretreatment mean serum EPCA levels were significantly higher in PCa patients than in controls (16.84±7.60 ng/ml vs. 4.12±2.05 ng/ml, P<0.001). Patients with locally advanced and metastatic PCa had significantly higher serum EPCA level than those with clinically localized PCa (22.93±5.28 ng/ml and 29.41±8.47 ng/ml vs. 15.17±6.03 ng/ml, P = 0.014 and P<0.001, respectively). Significantly elevated EPCA level was also found in metastatic PCa compared with locally advanced disease (P<0.001). Increased serum EPCA levels were significantly and positively correlated with Gleason score and clinical stage, but not with PSA levels and age. On multivariate analysis, pretreatment serum EPCA level held the most significantly predictive value for the biochemical recurrence and androgen-independent progression among pretreatment variables (HR = 4.860, P<0.001 and HR = 5.418, P<0.001, respectively).ConclusionsSerum EPCA level is markedly elevated in PCa. Pretreatment serum EPCA level correlates significantly with the poor prognosis, showing prediction potential for PCa progression.

The primary therapy chosen for patients with localized prostate cancer between the university hospital and its affiliated hospitals in Nara Uro-oncological research group registration

BackgroundWe investigated the differences between the preferential primary therapy conceived by the primary doctors and the primary therapy actually conducted for prostate cancer patients in Nara, Japan.MethodsThe distribution of primary therapy and clinical characteristics of 2303 prostate cancer patients - diagnosed between 2004 and 2006 at Nara Medical University and its 23 affiliated hospitals - were assessed. Moreover, the preferential primary therapy for the patients at each clinical stage (cT1-T3bN0M0) conceived by the primary doctors was investigated and compared to the actual therapy.ResultsOf all patients, 51% received primary androgen deprivation therapy (PADT), 30% underwent radical prostatectomy (RP), and 14% received radiation therapy (RT). The preferential primary therapy for cT1-2N0M0 was RP (92%) while 38% of the patients actually received PADT (RP: 40%). For cT3aN0M0, the preferential primary therapy was both RP and external beam radiation therapy (EBRT) while 58% of the patients actually received PADT (RP: 16%, EBRT: 24%). For cT3bN0M0, the most preferential primary therapy was EBRT (46%) while 67% of the patients actually received PADT (EBRT: 21%). This trend was more notable in the affiliated hospitals than in the University hospital. The hospitals with lower volume of RP per year significantly conducted PADT compared with those with higher volume of RP.ConclusionsPADT was commonly used to treat localized prostate cancer as well as locally advanced prostate cancer in Japan. There was a definite discrepancy between the preferential primary therapy conceived by the primary doctors and the actual therapy provided to the patients.

Clinical efficacy of primary combined androgen blockade for Japanese men with clinically localized prostate cancer unsuitable for local definitive treatment: a single institution experience

Primary hormonal therapy has been mostly used for patients with advanced prostate cancer, as international guidelines do not recommend its use for patients at earlier disease stages. However, there seems to be a discrepancy between the guideline recommendations and clinical practice on the use of primary androgen deprivation therapy for localized prostate cancer in Japan. Therefore, we retrospectively analyzed a single-institution experience in primary combined androgen blockade (CAB) for localized prostate cancer. The study included 187 patients with T1c-T3a prostate cancer unsuitable for local definitive treatment and treated with primary CAB. Clinical outcomes, predictive factors of PSA relapse and adverse events were investigated. The progression-free, disease-specific, and overall survival rates of all patients at 5 years were 63.0, 99.4 and 95.9%, respectively. Of the several parameters isolated as predictors of prostate-specific antigen (PSA) progression, nadir PSA level and the percentage of positive biopsy cores (%PBC) remained as independent prognostic factors on multivariate analysis. Toxicities were mild to moderate and well tolerated. Primary CAB treatment brought initial disease control without relapse in the majority of our selected cases. The %PBC may help predict time to relapse in the pretreatment setting. The results implicate that CAB can be an option as a primary treatment for clinically localized prostate cancer unsuitable for local definitive treatment. To confirm the exact efficacy of primary CAB, these findings should be reviewed in a large cohort of patients with long-term follow-up from various viewpoints, including disease control, toxicities, quality-of-life and medical cost.

Nadir PSA level and time to PSA nadir following primary androgen deprivation therapy are the early survival predictors for prostate cancer patients with bone metastasis

The purpose of this study was to identify the early predictor of survival for prostate cancer patients with bone metastasis. We reviewed 87 prostate cancer patients with bone metastasis who had received primary androgen deprivation therapy (PADT) at our institution. The medical records of the patients were examined with respect to laboratory data, pathological results, PSA response to PADT and clinical outcome. The overall survival (OS) rates were analyzed with reference to the nadir PSA level and time to PSA nadir (TTN) following PADT by Kaplan-Meier method. In all, 59 patients (67%) had progression to castration-resistant prostate cancer. Nadir PSA <0.2 ng ml(-1) (lower PSA nadir) during PADT were observed in 47 patients (54%). Multivariate analysis revealed that the extent of disease on bone scan (P=0.04), lower PSA nadir following PADT (P=0.003), albumin (P=0.04) and lactate dehydrogenase (P=0.01) were independent prognostic factors for survival. OS rates in the patients with lower PSA nadir were significantly higher. Longer TTN (>9 months) identified patients with prolonged OS in both lower and higher PSA nadir groups. PSA nadir <0.2 ng ml(-1) and prolonged TTN (>9 months) following PADT might be the most important early predictors for longer survival in prostate cancer patients with bone metastasis.

Abstract 4016: Upregulation of an orphan nuclear receptor TLX may contribute to the development of antiandrogen-resistant prostate cancer

Abstract The initial growth of most localized prostate cancers (PCa) is slow and dependent on androgens. Thus, early-staged and androgen-dependent cancer is manageable with prostatectomy and primary androgen deprivation therapy by either surgical or medical castration or monotherapy with antiandrogens. However, many prostate cancer patients under primary hormone therapy will relapse and further develop resistance to antiandrogen treatments and progress to a fatal androgen-independent and metastatic stage of which treatment options are limited. Identification of key factors or pathways responsible for the development of androgen-independence and antiandrogen resistance is crucial not only for better understanding of advanced prostate cancer development but also development of novel therapeutic strategies fro this cancer. Based on this background, we have established an antiandrogen-resistant prostate cancer cell line model (LNCaP-BC) by long-term treatment (&amp;gt;6 months) of an androgen-sensitive prostate caner cell line LNCaP with a non-steroidal antiandrogen bicalutamide at various concentrations. Our in vitro growth studies showed that LNCaP-BC cells behaved more malignant and grew aggressively. Compared to LNCaP cells, LNCaP-BC cells grew significantly faster than the untreated LNCaP cells in both normal and androgen-depleted media; were less sensitive to bicalutamide but more sensitive to low level of androgen (R1881); exhibited increased colony formation efficiencies in soft agar assay, enhanced tolerance to hypoxia environment and less sensitive to anticancer drug paclitaxel. Real-time PCR and Western blot results revealed that LNCaP-BC cells exhibited an increased mRNA and protein level of androgen receptor (AR) suggesting that the AR signaling was dysregulated in LNCaP-BC cells. More interestingly, a progressive and persistent up-regulation of an orphan nuclear receptor tailless TLX was observed in LNCaP-BC cells. To determine whether TLX overexpression would be associated with the antiandrogen resistant phenotype in prostate cancer cells, we generated stable-TLX transductants in LNCaP cells, which expressed low endogenous TLX level, by retroviral transduction. The in vitro growth phenotypes of LNCaP-TLX clones were similar to the LNCaP-BC cells, such as less sensitivity to bicalutamide and enhanced growth in charcoal-stripped serum, suggesting that TLX might play a regulatory role in the antiandrogen-resistance in advanced prostate cancer. In summary, we have established a bicalutamide-resistant in vitro model of prostate cancer. Our findings also revealed for the first time that up-regulation of TLX may play a regulatory role in the antiandrogen-resistance development of advanced prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4016. doi:10.1158/1538-7445.AM2011-4016

345 CONTEMPORARY NATIONALLY-REPRESENTATIVE TRENDS IN TREATMENT FOR LOCALIZED PROSTATE CANCER

INTRODUCTION AND OBJECTIVES: Primary treatment trends for localized prostate cancer, including substantial local variation, have previously been documented among selected community-based U.S. practices. We aimed to determine whether these trends are confirmed in larger, more broadly representative databases. METHODS: We analyzed treatments in two national administrative datasets including men covered by Medicare in 1998–2006 and by private insurance (i3 database) in 2002–2006. Treatment distributions were determined in each year among watchful waiting/active surveillance (WW), radical prostatectomy (RP), radiation therapy (RT), cryotherapy, and primary androgen deprivation therapy (PADT). Trends in specific modalities were further examined within RP and RT. County-level variation was assessed, and treatment predictors were determined using multinomial regression. RESULTS: Among 54,322 Medicare patients (mean age at diagnosis 75), WW use fell from 30% in 1998 to 22% in 2002 and remained low. PADT use peaked at 24% in 2002 and fell to 17% by 2006. RP use varied between 11% and 13% during the study period, while RT use rose from 35 to 44%. Laparoscopic/robot-assisted RP (LRRP) and intensity-modulated radiation therapy (IMRT) were both first reported in 1999, and rose to 35% of RP and 53% of RT cases, respectively, by 2006. Among 16,161 privately insured patients (mean age 65), WW and PADT fell steadily from 25% and 12% in 2002, respectively, to 12% and 7% in 2006. RT use varied between 30 and 32%, while RP use rose from 33 to 48%. LRRP and IMRT use rose from 1% and 15% of RP and RT cases, respectively, in 2002 to 41% and 48% in 2006. Use of neoadjuvant androgen deprivation therapy (NADT) declined among RP and brachytherapy patients, to 6 and 25%, respectively, among Medicare patients and to 2% and 22% among private insurance patients by 2006. Use of NADT rose to 41% and fell to 37% among external-beam RT patients with Medicare and private insurance, respectively. There was considerable geographic variation in treatment selection. Across counties, use of WW, PADT, RP, and RT ranged, respectively, from 3 to 55%, 0 to 48%, 0 to 50%, and 15 to 71%. Comorbidity, age, income, year of diagnosis, and county-level sociodemographic variables predicted treatment. CONCLUSIONS: These trends echo those documented in prior studies in smaller datasets, and these data confirm extensive geographic variation. In both databases, there is rapid, ongoing adoption of high-cost technologies among both RP and RT patients. These findings underscore the urgent need for high-quality cost-effectiveness research comparing these treatments.

Comorbidity and treatment regret in men with recurrent prostate cancer.

187 Background: To determine whether concurrent comorbidity is associated with treatment regret among men with PSA recurrence following primary therapy for prostate cancer. Methods: Among 795 men in the Comprehensive, Observational, Multicenter, Prostate Adenocarcinoma Registry (COMPARE) study who experienced PSA failure and were assessed a median of 5.5 (interquartile range 2.8-9.1) years after prostatectomy (n=410), external beam radiation (n=237), brachytherapy (n=124), or primary androgen deprivation (n=24), multivariable logistic regression was used to determine whether comorbidity level, sociodemographic factors, and other treatment factors were associated with treatment regret, as defined by a validated two-question screen. Significant comorbidity was defined as myocardial infarction, congestive heart failure, angina, diabetes, stroke, circulation problems, inflammatory bowel disease, or amputation. Results: Of 795 men, 14.8% reportedregret. Men with significant comorbidity were more likely to experience post-therapy bowel toxicity (p=0.029) and urinary problems (p=0.051). On multivariable analysis, significant comorbidity [adjusted odds ratio (AOR)=1.57 (95% CI:1.04-2.37); p = 0.033] and younger age [AOR: 0.965 (0.937-0.994) per year increase in age; p = 0.019] were associated with increased regret even after adjusting for post-therapy bowel and urinary complications. Conclusions: In a population of men with PSA recurrence, those with significant comorbidity were particularly prone to treatment regret, which highlights the growing importance of considering comorbidity when counseling patients about prostate cancer treatment options. To properly set expectations, such men should be informed about their potential for increased post-treatment toxicity, which may reduce their risk of regret if toxicity occurs, and serious consideration should be given to active surveillance. [Table: see text]

Comparative risk‐adjusted mortality outcomes after primary surgery, radiotherapy, or androgen‐deprivation therapy for localized prostate cancer

Comparative risk‐adjusted mortality outcomes after primary surgery, radiotherapy, or androgen‐deprivation therapy for localized prostate cancer

Erratum: Comparative risk‐adjusted mortality outcomes after primary surgery, radiotherapy, or androgen‐deprivation therapy for localized prostate cancer

NIH Public Access Author Manuscript Cancer. Author manuscript; available in PMC 2011 November 15. NIH-PA Author Manuscript Published in final edited form as: Cancer. 2010 November 15; 116(22): 5226–5234. doi:10.1002/cncr.25456. Comparative risk-adjusted mortality outcomes following primary surgery, radiation therapy, or androgen deprivation therapy for localized prostate cancer Matthew R. Cooperberg, MD, MPH (1),† , Andrew J. Vickers, PhD (2) , Jeanette M. Broering, RN, MS, MPH (1) , Peter R. Carroll, MD, MPH (1) , and the CaPSURE Investigators (1) Department of Urology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA Department of Epidemiology and Biostatistics, Memorial-Sloan Kettering Cancer Center, New York, NY NIH-PA Author Manuscript Abstract Purpose—No adequate randomized trials comparing active treatment modalities for localized prostate cancer have been reported. We analyzed risk-adjusted cancer-specific mortality outcomes among men undergoing radical prostatectomy, external-beam radiation therapy, or primary androgen deprivation therapy. Methods—The CaPSURE registry comprises men from 40 urologic practice sites followed prospectively under uniform protocols, regardless of treatment. 7538 men with localized disease were analyzed. Prostate cancer risk was assessed using the Kattan preoperative nomogram and the Cancer of the Prostate Risk Assessment (CAPRA) score, both well-validated instruments calculated from clinical data at the time of diagnosis. A parametric survival model was constructed to compare outcomes across treatments, adjusting for risk and age. NIH-PA Author Manuscript Results—226 men died of prostate cancer during followup. Adjusting for age and risk, the hazard ratio for cancer-specific mortality relative to prostatectomy was 2.21 (1.50–3.24) for radiation, and 3.22 (2.16–4.81) for androgen deprivation. Absolute differences between prostatectomy and radiation therapy were small for men at low risk, but increased substantially for men at intermediate and high risk. These results were robust to a variety of different analytic techniques including competing risks regression analysis, adjustment by CAPRA rather than Kattan score, and examination of overall survival as the endpoint. Conclusions—Prostatectomy for localized prostate cancer was associated with a significant and substantial reduction in mortality relative to radiation or androgen deprivation monotherapy. Although not a randomized study, given the multiple adjustments and sensitivity analyses it is unlikely that unmeasured confounding would account for the large observed differences in survival. Keywords prostate neoplasms; comparative effectiveness; surgery; radiation; hormonal therapy; CaPSURE To whom correspondence should be addressed: University of California, San Francisco, Box 1695, 1600 Divisadero St, A-607, San Francisco, CA 94143-1695, tel (415) 885-3660, fax (415) 885-7443, mcooperberg@urology.ucsf.edu.