Prostate ...

[Michael Scally MD]

Crook JM, O'Callaghan CJ, Duncan G, et al. Intermittent Androgen Suppression for Rising PSA Level after Radiotherapy. N Engl J Med 2012;367(10):895-903. Intermittent Androgen Suppression for Rising PS... [N Engl J Med. 2012] - PubMed - NCBI

Background Intermittent androgen deprivation for prostate-specific antigen (PSA) elevation after radiotherapy may improve quality of life and delay hormone resistance. We assessed overall survival with intermittent versus continuous androgen deprivation in a noninferiority randomized trial.

Methods We enrolled patients with a PSA level greater than 3 ng per milliliter more than 1 year after primary or salvage radiotherapy for localized prostate cancer. Intermittent treatment was provided in 8-month cycles, with nontreatment periods determined according to the PSA level. The primary end point was overall survival. Secondary end points included quality of life, time to castration-resistant disease, and duration of nontreatment intervals.

Results Of 1386 enrolled patients, 690 were randomly assigned to intermittent therapy and 696 to continuous therapy. Median follow-up was 6.9 years. There were no significant between-group differences in adverse events. In the intermittent-therapy group, full testosterone recovery occurred in 35% of patients, and testosterone recovery to the trial-entry threshold occurred in 79%. Intermittent therapy provided potential benefits with respect to physical function, fatigue, urinary problems, hot flashes, libido, and erectile function. There were 268 deaths in the intermittent-therapy group and 256 in the continuous-therapy group. Median overall survival was 8.8 years in the intermittent-therapy group versus 9.1 years in the continuous-therapy group (hazard ratio for death, 1.02; 95% confidence interval, 0.86 to 1.21). The estimated 7-year cumulative rates of disease-related death were 18% and 15% in the two groups, respectively (P=0.24).

Conclusions Intermittent androgen deprivation was noninferior to continuous therapy with respect to overall survival. Some quality-of-life factors improved with intermittent therapy.

 

[Michael Scally MD]

Batai K, Shah E, Murphy AB, et al. Fine-mapping of IL-16 gene and prostate cancer risk in African Americans. Cancer Epidemiology Biomarkers & Prevention. Fine-mapping of IL-16 gene and prostate cancer risk in African Americans

Background: Prostate cancer (Pca) is the most common type of cancer among men in the United States, and its incidence and mortality rates are disproportionate among ethnic groups. While genome-wide association studies of European descents have identified candidate loci associated with Pca risk, including a variant in IL16, replication studies in African Americans (AAs) have been inconsistent. Here we explore SNP variation in IL16 in AAs and test for association with Pca.

Methods: Association tests were performed for 2,257 genotyped and imputed SNPs spanning IL16 in 605 AA Pca cases and controls from Washington, DC. Eleven of them were also genotyped in a replication population of 1,093 AAs from Chicago. We tested for allelic association adjusting for age, global and local West African ancestry.

Results: Analyses of genotyped and imputed SNPs revealed that a cluster of IL16 SNPs were significantly associated with Pca risk. The strongest association was found at rs7175701 (P=9.8 x 10-8). In the Chicago population, another SNP (rs11556218) was associated with Pca risk (P=0.01). In the pooled analysis, we identified three independent loci within IL16 that were associated with Pca risk. SNP eQTL analyses revealed that rs7175701 is predicted to influence the expression of IL16 and other cancer related genes.

Conclusion: Our study provides evidence that IL16 polymorphisms play a role in Pca susceptibility among AAs.

Impact: Our findings are significant given that there has been limited focus on the role of IL16 genetic polymorphisms on Pca risk in AAs.

 

[Michael Scally MD]

Androgen-Deprivation Therapy For Prostate Cancer

Sartor O. Androgen deprivation - continuous, intermittent, or none at all? N Engl J Med 2012;367(10):945-6. Androgen deprivation - continuous, intermittent... [N Engl J Med. 2012] - PubMed - NCBI

There is a long history behind the study reported by Crook et al. in this issue of the Journal.(1) In 1941, Huggins and Hodges wrote about the first study of hormonal therapies for metastatic prostate cancer.(2) It was a remarkable observation: men with painful metastatic prostate cancer had a response to orchiectomy or estrogens, with dramatic symptom relief and declines in a circulating serum biomarker (acid phosphatase). Huggins deservedly was awarded the Nobel Prize in 1966. Few therapeutic advances in prostate cancer occurred from 1941 until the 1970s. In 1971, Andrew Schally and colleagues described the luteinizing hormone-releasing hormone.


Basaria S, Bhasin S. Targeting the skeletal muscle-metabolism axis in prostate-cancer therapy. N Engl J Med 2012;367(10):965-7. Targeting the skeletal muscle-metabolism axis i... [N Engl J Med. 2012] - PubMed - NCBI

Among men receiving androgen-deprivation therapy for prostate cancer, there is a high frequency of the metabolic syndrome and an increased risk of cardiovascular death. How the loss of anabolic signals leads to sarcopenia and metabolic abnormalities may be informative.

 

[Michael Scally MD]

Bosland MC. A Perspective on The Role of Estrogen in Hormone-Induced Prostate Carcinogenesis. Cancer Lett. ScienceDirect.com - Cancer Letters - A Perspective on The Role of Estrogen in Hormone-Induced Prostate Carcinogenesis

Androgens are thought to cause prostate cancer, but the precise mechanisms by which they do so are unclear. Data, mostly from animal studies, suggest that for androgens to cause prostate cancer they must be aromatized to estrogen and act in concert with these estrogen metabolites. Androgen-receptor mediated activity of androgens and estrogen receptor-mediated effects of estrogen metabolites are likely to be necessary, but estrogen genotoxicity appears to be a probable critical factor as well. Only when all these mechanisms are active, may prostate carcinogenesis result. Convincing proof-of-concept studies are needed to definitively test this concept which, if proven, may lead to clinically feasible chemoprevention approaches interfering with these mechanisms.

 

[Michael Scally MD]

Pastuszak AW, Pearlman AM, Godoy G, Miles BJ, Lipshultz LI, Khera M. Testosterone replacement therapy in the setting of prostate cancer treated with radiation. Int J Impot Res. International Journal of Impotence Research - Abstract of article: Testosterone replacement therapy in the setting of prostate cancer treated with radiation

A lack of consensus and few data support testosterone replacement therapy (TRT) in hypogonadal men who have been treated for prostate cancer (CaP), particularly those who have received radiation therapy. We performed retrospective review of 13 hypogonadal men with CaP, treated with brachytherapy or external beam radiotherapy who were subsequently treated with testosterone (T) between 2006 and 2011. Serum T, free T (FT), estrogen (E), sex hormone-binding globulin (SHBG), prostate-specific antigen (PSA), hemoglobin (Hgb) and hematocrit (Hct) values were evaluated approximately every 3 months after TRT initiation up to 67 months of follow-up. Prostate biopsies demonstrated four men with Gleason (Gl) 6, 7 with Gl 7 and 2 with Gl 8 disease. Median (interquartile range) age at TRT initiation was 68.0 (62.0-77.0) years, initial T 178.0 (88.0-263.5) ng dl(-1), FT 10.1 (5.7-15.0) pg ml(-1) and PSA 0.30 (0.06-0.95) ng ml(-1). Median follow-up after TRT initiation was 29.7 months (range 2.3-67.3 months). At median follow-up, a significant increase in mean T (368.0 (281.3-591.0) ng dl(-1), P=0.012) and SHBG were observed, with no significant increases in Hgb, Hct, E, FT, or PSA (0.66 (0.16-1.35) ng ml(-1), P=0.345). No significant increases in PSA or CaP recurrences were observed at any follow-up interval. TRT in the setting of CaP after treatment with radiation therapy results in a rise in serum T levels and improvement in hypogonadal symptoms without evidence of CaP recurrence or progression.

 

[BBC3]

NOW THATS SUM FUKIN GREEK....

Are you thinking they said that in men who have had their prostate IRRADIATED due to cancer, and have replaced hormones with TRT, that the PSA has not risen..

1. not risen, But from what?
2. what is that? 13 or 16 subjects - I dont even recall.
3. I did note that all their TT levels seemed low at 178..?! And proposed interpreted as prior to radiation treatment as well as immediate post.
4. Where did they find Uro's with the balls or insanity to apply TRT to post radiological subjects with PC...???!!!!!
5. So the study speaks of the 2.5 year mark post INITIAL radiation therapy I can assume?
6. But if you note, they do not even discern whether or not THE SUBJECT IS STILL ALIVE....
7. They TOTALLY discount the point that they are INFERRING as a RISE in serum TT is remarkably a GOOD thing.
8. The complete subject completely again omits the whole point the SERUM MEANS SQUAT... Sorry.. Just sayin...:drooling:

Pastuszak AW, Pearlman AM, Godoy G, Miles BJ, Lipshultz LI, Khera M. Testosterone replacement therapy in the setting of prostate cancer treated with radiation. Int J Impot Res. International Journal of Impotence Research - Abstract of article: Testosterone replacement therapy in the setting of prostate cancer treated with radiation

A lack of consensus and few data support testosterone replacement therapy (TRT) in hypogonadal men who have been treated for prostate cancer (CaP), particularly those who have received radiation therapy. We performed retrospective review of 13 hypogonadal men with CaP, treated with brachytherapy or external beam radiotherapy who were subsequently treated with testosterone (T) between 2006 and 2011. Serum T, free T (FT), estrogen (E), sex hormone-binding globulin (SHBG), prostate-specific antigen (PSA), hemoglobin (Hgb) and hematocrit (Hct) values were evaluated approximately every 3 months after TRT initiation up to 67 months of follow-up. Prostate biopsies demonstrated four men with Gleason (Gl) 6, 7 with Gl 7 and 2 with Gl 8 disease. Median (interquartile range) age at TRT initiation was 68.0 (62.0-77.0) years, initial T 178.0 (88.0-263.5) ng dl(-1), FT 10.1 (5.7-15.0) pg ml(-1) and PSA 0.30 (0.06-0.95) ng ml(-1). Median follow-up after TRT initiation was 29.7 months (range 2.3-67.3 months). At median follow-up, a significant increase in mean T (368.0 (281.3-591.0) ng dl(-1), P=0.012) and SHBG were observed, with no significant increases in Hgb, Hct, E, FT, or PSA (0.66 (0.16-1.35) ng ml(-1), P=0.345). No significant increases in PSA or CaP recurrences were observed at any follow-up interval. TRT in the setting of CaP after treatment with radiation therapy results in a rise in serum T levels and improvement in hypogonadal symptoms without evidence of CaP recurrence or progression.

 

[Michael Scally MD]

Dai B, Qu Y, Kong Y, et al. Low pretreatment serum total testosterone is associated with a high incidence of Gleason score 8-10 disease in prostatectomy specimens: data from ethnic Chinese patients with localized prostate cancer. BJU Int. Low pretreatment serum total testosterone is associated with a high incidence of Gleason score 8–10 disease in prostatectomy specimens: data from ethnic Chinese patients with localized prostate cancer - Dai - 2012 - BJU International - Wiley On

Study Type - Prognosis (prospective cohort)
Level of Evidence 2b

What's known on the subject? and What does the study add?
Previous data from clinically localized prostate cancer (PCa) series treated with radical prostatectomy (RP) have suggested that low preoperative serum total testosterone level is associated with more aggressive PCa; however, the definition of low preoperative total testosterone level varied among these studies (from 220 ng/dL to 387 ng/dL). Moreover, no relevant data exist in the literature regarding ethnic Chinese patients. The study shows that the most widely used threshold for low pretreatment total testosterone level (total testosterone < 300 ng/dL) is not appropriate for ethnic Chinese patients, because it could not distinguish patients with more aggressive PCa from those with less aggressive disease. Setting the threshold at the level of total testosterone < 250 ng/dL works better, because pretreatment total testosterone < 250 ng/dL is associated with a significantly higher incidence of Gleason score 8-10 disease in RP specimens.

OBJECTIVE: * To investigate the relationship between preoperative serum total testosterone level and prognostic factors of Chinese patients with clinically localized prostate cancer (PCa).

PATIENTS AND METHODS: * A total of 110 patients with localized PCa, treated by radical prostatectomy (RP), were included in this prospective study. * Clinical and pathological data from each patient were collected. Total testosterone was measured on the morning of surgery. * Total testosterone levels for each patient were compared using two thresholds: threshold 1 (total testosterone <300 ng/dL vs total testosterone >/=300 ng/dL) and threshold 2 (total testosterone <250 ng/dL vs total testosterone >/=250 ng/dL).

RESULTS: * The median preoperative total testosterone level was 346 ng/dL. Gleason scores of </=6, 7 and >/=8 were found in the RP specimens from 21 (19.1%), 67 (60.9%) and 22 (20.0%) patients, respectively. * Compared with those with low grade disease, patients with high grade disease (Gleason score >/= 8) in RP specimens had a significantly lower preoperative total testosterone. * When comparing 35 patients with hypogonadism with 75 patients with eugonadism, classified by threshold 1, no significant relationships were found. * When comparing 18 patients with hypogonadism with 92 patients with eugonadism, classified by threshold 2, pathological Gleason score >/= 8 tumours were more common in patients with hypogonadism.

CONCLUSION: * Setting the threshold for hypogonadism at the level of pretreatment serum total testosterone <250 ng/dL is appropriate for ethnic Chinese patients with localized PCa, because patients with pretreatment total testosterone <250 ng/dL are associated with a higher incidence of Gleason score 8-10 disease in RP specimens.

 

[Michael Scally MD]

Dumas L, Payne H, Chowdhury S. The evolution of antiandrogens: MDV3100 comes of age. Expert Rev Anticancer Ther 2012;12(2):131-3. An Error Occurred Setting Your User Cookie / An Error Occurred Setting Your User Cookie

 

[Michael Scally MD]

Niraula S, Chi K, Joshua AM. Beyond castration-defining future directions in the hormonal treatment of prostate cancer. Horm Cancer 2012;3(1-2):3-13. http://www.springerlink.com/content/a254155155154u02/fulltext.pdf

It is now almost 70 years since Charles Huggins described the relationship between testosterone and the prostate gland. Arguably defining one of the first targeted therapies, the reduction of testosterone to castrate levels remains unaltered as the standard of care for men with metastatic prostate cancer. The failure of castration to permanently control the growth of prostate cancer leads to a state called castration-resistant prostate cancer (CRPC). Whilst numerous mechanisms have been suggested for the emergence of castration resistance [Scher and Sawyers (J Clin Oncol 23(32):8253-8261, 2005); Chen et al. (Curr Opin Pharmacol 8(4):440-448, 2008), Pienta and Bradley (Clin Cancer Res 12(6):1665-1671, 2006); Feldman and Feldman (Nat Rev Cancer 1(1):34-45, 2001); Mostaghel and Nelson (Best Pract Res Clin Endocrinol Metab 22(2):243-258, 2008)], a greater understanding of prostate cancer biology suggests that many such cancers retain a dependency on androgens and endeavour to increase bioavailable androgens through mechanisms such as AR amplification and intracrine androgen synthesis [Mohler et al. (Clin Cancer Res 10(2):440-448, 2004); Attard et al. (Clin Cancer Res 17(7):1649-1657, 2011); Hu et al. (Expert Rev Endocrinol Metab 5(5):753-764, 2010)]. With the recent approval of abiraterone acetate (Zytiga) and the pending approval of MDV3100, this article previews the future directions in clinical development and issues that will arise with the next generation of androgen-targeted agents.

 

[Michael Scally MD]

Phytotherapy – [NO] Application in Benign Prostatic Hyperplasia and Prostate Adenocarcinoma

Moran E, Budia A, Broseta E, Boronat F. Phytotherapy in Urology. Current Scientific Evidence of its Application in Benign Prostatic Hyperplasia and Prostate Adenocarcinoma. Actas Urol Esp. http://www.elsevier.es/sites/default/files/elsevier/eop/S0210-4806%2812%2900305-1.pdf

OBJECTIVE: To evaluate the usefulness of phytotherapy in the treatment of the benign prostatic hyperplasia (BPH) and prostatic adenocarcinoma (ADCP).

ACQUISITION OF EVIDENCE: Systematic review of the evidence published until January 2011 using the following scientific terms: phytotherapy, benign prostate hyperplasia, prostatic adenocarcinoma, prostate cancer and the scientific names of compounds following the rules of the International Code of Botanical Nomenclature. The databases used were Medline and The Cochrane Library. We included articles published until January 2011 written in English and Spanish. We included studies in vitro/in vivo on animal models or human beings. Exclusion criteria were literature not in English and Spanish or articles with serious methodological flaws.

SYNTHESIS OF THE EVIDENCE: We included 65 articles of which 40 met the inclusion criteria. BPH: the most studied products are serenoa repens and pygeum africanum. There are many studies in favour of the use of phytotherapy but its conclusions are inconsistent due to the small number of patients, the lack of control with placebo or short follow-up. However the use of these products is common in our environment. ADCP: there is no evidence to recommend phytotherapy in the treatment of the ADCP. There are works on prevention but only at experimental level so there is no evidence for its recommendation.

CONCLUSIONS: The scientific evidence on the use of phytotherapy in prostatic pathology is conclusive not recommending the use of it for BPH or the ADCP.

 

[Michael Scally MD]

Killian PH, Kronski E, Michalik K, et al. Curcumin Inhibits Prostate Cancer Metastasis in vivo by Targeting the Inflammatory Cytokines CXCL1 and -2. Carcinogenesis. Curcumin Inhibits Prostate Cancer Metastasis in vivo by Targeting the Inflammatory Cytokines CXCL1 and -2

In America and Western Europe prostate cancer is the second leading cause of death in men. Emerging evidence suggests that chronic inflammation is a major risk factor for the development and metastatic progression of prostate cancer.

We previously reported that the chemopreventive polyphenol Curcumin inhibits the expression of the pro-inflammatory cytokines CXCL1 and -2 leading to diminished formation of breast cancer metastases. Here we analyse the effects of Curcumin on prostate carcinoma growth, apoptosis and metastasis. We show that Curcumin inhibits translocation of NF?B to the nucleus through the inhibition of the I?B-kinase, IKK?, leading to stabilization of the inhibitor of NF?B, I?B?, in PC3 prostate carcinoma cells. Inhibition of NF?B activity reduces expression of CXCL1 and -2 and abolishes the autocrine/paracrine loop that links the two chemokines to NF?B. The combination of Curcumin with the synthetic IKK? inhibitor, SC-541, shows no additive or synergistic effects indicating that the two compounds share the target. Treatment of the cells with Curcumin as wells as siRNA based knock-down of CXCL1 and -2 induce apoptosis, inhibit proliferation, and down-regulate several important metastasis-promoting factors like COX2, SPARC, and EFEMP. In an orthotopic mouse model of haematogenous metastasis, treatment with Curcumin inhibits statistically significantly formation of lung metastases.

In conclusion, chronic inflammation can induce a metastasis prone phenotype in prostate cancer cells by maintaining a positive pro-inflammatory and pro-metastatic feedback loop between NF?B and CXCL1/-2. Curcumin disrupts this feedback loop by the inhibition of NF?B signalling leading to reduced metastasis formation in vivo.

 

[Michael Scally MD]

Prostate Patients Suffer as Money Overwhelms Best Therapy
Prostate Patients Suffer as Money Overwhelms Best Therapy - Businessweek

“IMRT [ intensity- modulated radiation therapy] is overused, period,” said urologist Matthew Cooperberg of the University of California, San Francisco, who has authored at least 18 studies on prostate treatment.

Cooperberg estimates that about half the 50,000 men who receive IMRT for prostate cancer each year don’t need it or don’t gain anything from it that exceeds cheaper treatment, resulting in about $1 billion of overspending.

“Doctors do what they’re paid to do” Cooperberg said. “If you tell them they can earn $2,000 for surgery or $37,000 for IMRT, what do you think will happen?”

 

[Michael Scally MD]

Lee SH, Chung MS, Kim JH, Oh YT, Rha KH, Chung BH. Magnetic resonance imaging targeted biopsy in men with previously negative prostate biopsy results. J Endourol 2012;26(7):787-91. An Error Occurred Setting Your User Cookie

PURPOSE: To evaluate the efficacy of targeted prostate biopsy using magnetic resonance imaging (MRI) and to characterize clinicopathologic features of tumors detected with targeted prostate biopsy in men with previous negative prostate biopsy results.

PATIENTS AND METHODS: We prospectively studied 87 patients with a persistently increasing level of serum prostate-specific antigen (PSA), at least one previous set of negative 12-core prostate biopsies, and normal digital rectal examination. All patients were examined with combined T2-weighted and diffusion-weighted MRI before undergoing the prostate biopsy. Prostate biopsy was performed using transrectal ultrasonography-guided standard 12 cores plus targeted biopsy to suspicious region(s) as identified on T2 images on their MRI.

RESULTS: Of a total of 87 cases, 82 (94.2%) patients had suspicious lesion(s) on their MRI. Of these 82 patients, 46 (56.0%) patients had prostate cancer (PCA) as determined by the biopsy. The patients with PCA showed a significantly higher incidence of having suspicious lesion(s) (the anterior or apex) on MRI than the patients without PCA (P<0.05). On analysis by dividing all biopsy cores into the targeted cores and standard cores, PCA was found in 149/518 (28.8%) MRI-targeted cores and in 32/903 (3.6%) standard cores (P=0.012) Of 43 patients who underwent radical prostatectomy, 37 (86.0%) patients were detected with PCA located at the anterior or apex portion of the prostate. For tumor characteristics according to tumor locations, there was no significant correlation between tumor location and Gleason scores or pathologic stage.

CONCLUSIONS: Our data suggest that a MRI-targeted prostate biopsy after prostate MRI might be considered for the identification of cancer foci and the detection of PCA, for patients with a previous negative standard prostate biopsy result despite a persistently elevated PSA value.

 

[BBC3]

so what then,? Is a robot doin the poke too? Docs still gotta line it up..

There are some facets in life that the fine precision and human touch will never be replaced. Another is customer service... LOL

Lee SH, Chung MS, Kim JH, Oh YT, Rha KH, Chung BH. Magnetic resonance imaging targeted biopsy in men with previously negative prostate biopsy results. J Endourol 2012;26(7):787-91. An Error Occurred Setting Your User Cookie

PURPOSE: To evaluate the efficacy of targeted prostate biopsy using magnetic resonance imaging (MRI) and to characterize clinicopathologic features of tumors detected with targeted prostate biopsy in men with previous negative prostate biopsy results.

PATIENTS AND METHODS: We prospectively studied 87 patients with a persistently increasing level of serum prostate-specific antigen (PSA), at least one previous set of negative 12-core prostate biopsies, and normal digital rectal examination. All patients were examined with combined T2-weighted and diffusion-weighted MRI before undergoing the prostate biopsy. Prostate biopsy was performed using transrectal ultrasonography-guided standard 12 cores plus targeted biopsy to suspicious region(s) as identified on T2 images on their MRI.

RESULTS: Of a total of 87 cases, 82 (94.2%) patients had suspicious lesion(s) on their MRI. Of these 82 patients, 46 (56.0%) patients had prostate cancer (PCA) as determined by the biopsy. The patients with PCA showed a significantly higher incidence of having suspicious lesion(s) (the anterior or apex) on MRI than the patients without PCA (P<0.05). On analysis by dividing all biopsy cores into the targeted cores and standard cores, PCA was found in 149/518 (28.8%) MRI-targeted cores and in 32/903 (3.6%) standard cores (P=0.012) Of 43 patients who underwent radical prostatectomy, 37 (86.0%) patients were detected with PCA located at the anterior or apex portion of the prostate. For tumor characteristics according to tumor locations, there was no significant correlation between tumor location and Gleason scores or pathologic stage.

CONCLUSIONS: Our data suggest that a MRI-targeted prostate biopsy after prostate MRI might be considered for the identification of cancer foci and the detection of PCA, for patients with a previous negative standard prostate biopsy result despite a persistently elevated PSA value.

 

[Michael Scally MD]

so what then,? Is a robot doin the poke too? Docs still gotta line it up..

There are some facets in life that the fine precision and human touch will never be replaced. Another is customer service... LOL

Actually, the biopsy is guided literally by the MRI finding. At this time, I believe there are two MRI systems. Artemis being one.

 

[Michael Scally MD]

Cersosimo RJ. New Agents for the Management of Castration-Resistant Prostate Cancer (November). Ann Pharmacother. http://www.theannals.com/content/early/2012/11/06/aph.1R169.abstract

OBJECTIVE: To review the activity of 3 new agents approved for the management of advanced castration-resistant prostate cancer (CRPC): sipuleucel-T, cabazitaxel, and abiraterone acetate.

DATA SOURCES: Literature was accessed through MEDLINE (1977-June 2012) and abstracts from the American Society of Clinical Oncology (2000-2012) using the terms castration-resistant and hormone-refractory prostate cancer, sipuleucel-T, cabazitaxel, abiraterone, Provenge, Jevtana, and Zytiga. Reference citations from publications identified were also reviewed.

STUDY SELECTION AND DATA EXTRACTION: Articles identified from the DATA SOURCES: Options for patients with CRPC have been limited, with little to offer those who failed or could not tolerate docetaxel-based therapy. Three new drugs, with very different mechanisms of action, have changed that and will undoubtedly change the treatment paradigm for these patients. Each agent has demonstrated an impact on patient survival. Sipuleucel-T, the first immunotherapy approved for treatment of CRPC, improved median overall survival by 4.1 months and reduced the risk of death by 22% in a placebo-controlled trial of asymptomatic patients. Sipuleucel-T can be administered prior to docetaxel-based therapy. Cabazitaxel, a taxane chemotherapy agent, improved median overall survival by 2.4 months and reduced the risk of death by 30% in a Phase 3 trial of patients whose cancer progressed during or after docetaxel-based therapy. Abiraterone acetate, a hormonal therapy, improved median overall survival by 3.9 months and reduced the risk of death by 35% in patients with relapse during or after docetaxel-based therapy.

CONCLUSIONS: The advent of new agents for the management of advanced CRPC has increased the choices for patients whose options were limited. Additional experience will determine the optimal sequencing of these agents, their roles in combination therapy, and their activity in patients with earlier disease.

 

[Michael Scally MD]

Kim HS, Lee CY, Lim DH, Kim CS, Baik S. The Prostate Cancer Detection Rate on the Second Prostate Biopsy according to Prostate-Specific Antigen Trend. Korean J Urol 20212;53(10):686-90. http://www.kjurology.org/Synapse/Data/PDFData/0020KJU/kju-53-686.pdf

PURPOSE: To identify the prostate cancer detection rate on the patients who had second prostate biopsy out of the patients who were reported negative in their first biopsy.

MATERIALS AND METHODS: From July 2006 to February 2012, prostate biopsy was performed on 843 patients with over 4 ng/ml and on 618 biopsy negative patients PSA was performed from between 6 months and 9 months after biopsy. On 164 patients, second biopsy was performed, and 42 patients were selected. If there was less than 10% change between PSA before the prostate biopsy and PSA measured during 6 to 9 months after the first biopsy it was considered as no change. If above 10% increase, it was considered increase and if above 10% decrease it was considered as decrease.

RESULTS: The cancer detection rate in PSA increase group was 20%, the detection rate in no change in PSA level but still over the normal range group 8.3%, and that in the PSA decrease group was 0%. When comparing prostate cancer group and non-cancer group, it is more probable to have prostate cancer when they are older, prostate volume is smaller and PSA density is higher.

CONCLUSIONS: The second biopsy is strongly recommended when PSA level shows no change or increase, age is older, prostate volume is smaller or PSA density is higher.

 

[Michael Scally MD]

Horie S. Chemoprevention of Prostate Cancer: Soy Isoflavones and Curcumin. Korean J Urol 2012;53(10):665-72. http://www.kjurology.org/Synapse/Data/PDFData/0020KJU/kju-53-665.pdf

The burden of increasing morbidity and mortality due to prostate cancer imposes a need for new, effective measures of prevention in daily life. The influence of lifestyle on carcinogenesis in Asian men who migrate to Western cultures supports a causal role for dietary, environmental, and genetic factors in the epidemiology of prostate cancer. Chemoprevention, a prophylactic approach that uses nontoxic natural or synthetic compounds to reverse, inhibit, or prevent cancer by targeting specific steps in the carcinogenic pathway, is gaining traction among health care practitioners. Soy isoflavones and curcumin, staples of the Asian diet, have shown promise as functional factors for the chemoprevention of prostate cancer because of their ability to modulate multiple intracellular signaling pathways, including cellular proliferation, apoptosis, inflammation, and androgen receptor signaling. Recent evidence has revealed the DNA damage response (DDR) to be one of the earliest events in the multistep progression of human epithelial carcinomas to invasive malignancy. Soy isoflavones and curcumin activate the DDR, providing an opportunity and rationale for the clinical application of these nutraceuticals in the chemoprevention of prostate cancer.

 

[Michael Scally MD]

Kjellman A, Friis S, Granath F, Gustafsson O, Sorensen HT, Akre O. Treatment with finasteride and prostate cancer survival. Scand J Urol Nephrol. An Error Occurred Setting Your User Cookie

Objective. This study compared survival after diagnosis of prostate cancer (PC) in men previously treated with finasteride, in men previously treated with alpha-adrenoceptor antagonists, in men treated with both, and in men who had received neither type of medication.

Material and methods. In total, 3791 men diagnosed with PC in northern Denmark were identified. The region's prescription database was used to identify all men prescribed finasteride and alpha-adrenoceptor antagonists and those who had received neither medication during the period 1989-2001. Among men with a diagnosis of PC, overall survival and disease-specific survival were assessed after diagnosis using Cox proportional hazards regression. The risk of being diagnosed with non-localized PC was estimated using conditional logistic regression.

Results. The adjusted hazard ratio (HR) for PC death and overall death after treatment with finasteride was 0.93 [95% confidence interval (CI) 0.76-1.14] and 0.92 (95% CI 0.77-1.10), respectively. Treatment with alpha-adrenoceptor antagonists was associated with a reduced risk of PC death and overall death (HR 0.78, 95% CI 0.67-0.90, and 0.82, 95% CI 0.73-0.93, respectively. The risk of being diagnosed with non-localized PC was increased for men taking finasteride (odds ratio 1.14, 95% CI 1.01-1.29) per 100 defined daily doses.

Conclusions. Treatment with finasteride prior to a diagnosis of PC did not affect PC-specific survival, but increased the risk of being diagnosed with non-localized disease. Treatment with alpha-adrenoceptor antagonists was associated with better cause-specific survival and lower risk of non-localized disease.

 

[Michael Scally MD]

Colbert JA, Adler JN. Prostate Cancer Screening - Polling Results. New England Journal of Medicine 2012;367(17):e25. MMS: Error

In August, we presented a case involving a 55-year-old man seeking guidance from his primary care physician on whether to pursue screening for prostate cancer with a yearly digital rectal examination and prostate-specific antigen (PSA) testing in Clinical Decisions,1 an interactive feature designed to assess how readers would manage a clinical problem for which there may be more than one appropriate approach to the care of patients. Two experts in the field presented arguments, one in favor of PSA testing and one opposed. We asked our readers to decide between these two approaches and to share their thoughts on this controversial topic.

We received 958 votes from readers in 67 countries. A little over half (55%) of all voters recommended PSA screening for the man in our clinical vignette — a split that revealed the lack of clinical consensus surrounding this important issue. North American voters preferred to screen with PSA testing: 59% of 489 voters from the United States and 67% of 46 Canadians voted in favor of PSA screening. European voters were less enthusiastic, with only 47% of 217 voters in favor of PSA screening.

We also received 91 comments, with 71% of the comments written in favor of PSA screening — a much higher percentage than that in the voting alone. A large number of comments stressed the importance of informed and shared decision making between the patient and his physician. Many physicians believe strongly that the best way to approach PSA screening is to have a detailed discussion with the patient about screening options and treatment options, including the possibility of not treating a low-grade tumor (i.e., watchful waiting). In agreeing to screening, a patient must realize that he is also agreeing to the possibility that a prostate biopsy will be performed if the PSA value is elevated. Depending on the results of the biopsy, the patient may be advised to undergo surgery or radiation treatment — with potential adverse effects, including erectile dysfunction and incontinence.

A large number of respondents remarked that they recommended PSA screening on the basis of personal experience with elevated PSA levels that led to life saving treatment. Other respondents believed that data from the European Randomized Study of Screening for Prostate Cancer2 provide compelling evidence that PSA screening saves lives. Finally, a number of comments touched on patients' fears with regard to cancer diagnosis, and some clinicians were of the opinion that measuring the PSA level can reassure a patient that his physician is actively performing surveillance.

The comments against PSA screening focused on widespread overdiagnosis and overtreatment of an often indolent disease that is life-threatening in only a minority of patients. Some comments highlighted the side effects produced by these treatments, including erectile dysfunction and incontinence. Finally, we received comments that cited conflicting data from prostate-cancer screening trials as evidence that PSA screening does not have a meaningful effect on mortality.

These polling results and comments reflect a lack of consensus within the medical field on the best approach to prostate-cancer screening. Future research may help settle this polarizing debate, but as clinicians we should be grateful for recent contributions from high-quality studies — even if the results are not all coincident. In the meantime, physicians should maintain an informed, sensitive balance in counseling patients regarding the decision whether to pursue PSA testing.