Prostate ...

[Michael Scally MD]

Do dietary calcium and vitamin D matter in men with prostate cancer?

Active surveillance (AS) is an attractive alternative to immediate treatment for men with low-risk prostate cancer.

Thus, the identification of environmental factors that promote the progression of indolent disease towards aggressive stages is critical to optimize clinical management.

Epidemiological studies suggest that calcium-rich diets contribute to an increased risk of developing prostate cancer and that vitamin D reduces this risk.

However, the potential effect of these nutrients on the progression of early-stage prostate tumours is uncertain, as studies in this setting are scarce and have not provided unambiguous conclusions.

By contrast, the results of a preclinical study from our own group demonstrate that a diet high in calcium dose-dependently accelerated the progression of early-stage prostate tumours and that dietary vitamin D prevented this effect.

The extent to which the conclusions of preclinical and epidemiological studies support a role for calcium and vitamin D and the relevance of monitoring and adjustment of calcium and/or vitamin D intake in patients on AS require further investigation.

Capiod T, Barry Delongchamps N, Pigat N, Souberbielle J-C, Goffin V. Do dietary calcium and vitamin D matter in men with prostate cancer? Nature Reviews Urology 2018;15:453-61. Do dietary calcium and vitamin D matter in men with prostate cancer? | Nature Reviews Urology

 

[Michael Scally MD]

Rodriguez KM, Pastuszak AW, Khera M. The Role of Testosterone Therapy in the Setting of Prostate Cancer. Curr Urol Rep 2018;19:67. The Role of Testosterone Therapy in the Setting of Prostate Cancer

PURPOSE OF REVIEW: The role of testosterone in the development of prostate cancer and the safety of testosterone therapy (TTh) after prostate cancer treatment, or in the setting of active surveillance, remains controversial. There are many concerns about using TTh in men, particularly those with a history of prostate cancer, ranging from a possible increased risk of cardiovascular disease to cancer progression or recurrence.

With many prostate cancer patients living longer, and hypogonadism having significant morbidity, much care must go into the decision to treat. Here, we review the literature investigating the effects of testosterone on the prostate as well as the efficacy and safety of exogenous testosterone in men with a history of prostate cancer.

RECENT FINDINGS: The improvement in quality of life with TTh is well studied and understood, while the argument for significantly increased risk of cancer or other adverse effects is much less robust. Neither increased rates of prostate cancer, cancer recurrence, or cardiovascular risk have been well established. In men with high-risk prostate cancer, evidence in the setting of TTh is very limited, and TTh should be used with caution.

SUMMARY: The fears of TTh causing or worsening prostate cancer do not appear to be well supported by available data. Though more studies are needed to definitively determine the safety of TTh in men with prostate cancer, consideration should be given to treatment of hypogonadal men with a history of CaP.

 

[Michael Scally MD]

Lower Circulating Androgens Are Associated with Overall Cancer Risk and Prostate Cancer Risk

Androgens, notably testosterone (T), have been implicated in development of several common cancers and prostate cancer; however, precise mechanisms remain unclear. This study assessed prospective associations of serum T, dihydrotestosterone (DHT) and estradiol (E2) with overall cancer (excluding skin cancer), prostate, colorectal and lung cancer risk in 1574 community-dwelling men aged 25–84 years.

Sex hormones were assayed using mass spectrometry and men were followed for 20 years with outcomes ascertained using data linkage. Over 20 years, there were 289, 116, 48 and 22 men who developed any cancer, prostate cancer, colorectal cancer and lung cancer, respectively.

Androgens in the lowest quartile were associated with an increased overall cancer risk (HR = 1.36, 95% CI 1.05–1.76, p = 0.020 for T; and HR = 1.30, 95% CI 1.00–1.69, p = 0.049 for DHT comparing the lowest vs other quartiles). T in the lowest quartile was associated with an increased risk of prostate cancer (HR = 1.53, 95% CI 1.02–2.29, p = 0.038 comparing the lowest vs other quartiles). The association between androgens and overall cancer risk remained similar after excluding prostate cancer outcomes; however, results were not significant.

There were no associations of T, DHT or E2 with colorectal or lung cancer risk; however, LH in the highest quartile was associated with an increased risk of lung cancer (HR = 4.55, 95% CI 1.70–12.19, p = 0.003 for the highest vs other quartiles).

Whether T is a biomarker of poor health in men with any cancer or prostate cancer requires further confirmation as does the nature and mechanism of the association of a high LH with future lung cancer.

Chan YX, Knuiman MW, Divitini ML, Handelsman DJ, Beilby JP, Yeap BB. Lower Circulating Androgens Are Associated with Overall Cancer Risk and Prostate Cancer Risk in Men Aged 25–84 Years from the Busselton Health Study. Hormones and Cancer 2018. https://doi.org/10.1007/s12672-018-0346-5

 

[Michael Scally MD]

Estrogens and Prostate Cancer

BACKGROUND: Hormonal influences such as androgens and estrogens are known contributors in the development and progression of prostate cancer (CaP). While much of the research to the hormonal nature of CaP has focused on androgens, estrogens also have critical roles in CaP development, physiology as well as a potential therapeutic intervention.

METHODS: In this review, we provide a critical literature review of the current basic science and clinical evidence for the interaction between estrogens and CaP.

RESULTS: Estrogenic influences in CaP include synthetic, endogenous, fungi and plant-derived compounds, and represent a family of sex hormones, which cross hydrophobic cell membranes and bind to membrane-associated receptors and estrogen receptors that localize to the nucleus triggering changes in gene expression in various organ systems.

CONCLUSIONS: Estrogens represent a under-recognized contributor in CaP development and progression. Further research in this topic may provide opportunities for identification of environmental influencers as well as providing novel therapeutic targets in the treatment of CaP.

Dobbs RW, Malhotra NR, Greenwald DT, Wang AY, Prins GS, Abern MR. Estrogens and prostate cancer. Prostate Cancer Prostatic Dis 2018. Estrogens and prostate cancer

 

[Michael Scally MD]

Tikkinen KAO, Dahm P, Lytvyn L, et al. Prostate cancer screening with prostate-specific antigen (PSA) test: a clinical practice guideline. BMJ 2018;362. Prostate cancer screening with prostate-specific antigen (PSA) test: a clinical practice guideline

What you need to know

· PSA testing has increased the number of men diagnosed with and treated for prostate cancer, but many of these men would never have experienced any symptoms or death from prostate cancer

· This guideline makes a weak recommendation against offering systematic PSA screening based on an updated systematic review. The recommendation is weak because there may be a small, though uncertain, benefit of screening on prostate cancer mortality

· Men who place more value on avoiding complications from biopsies and cancer treatment are likely to decline screening. In contrast, men who put more value in even a small reduction of prostate cancer mortality (such as men at high baseline risk because of family history or African descent, or those concerned to rule out the diagnosis) may opt for screening

· Shared decision making is needed for men considering screening to make a decision consistent with their individual values and preferences. However, clinicians need not feel obligated to systematically raise the issue of PSA screening with their patients

What is the role of prostate-specific antigen (PSA) screening in prostate cancer? An expert panel produced these recommendations based on a linked systematic review.1 The review was triggered by a large scale, cluster randomised trial on PSA screening in men without a previous diagnosis of prostate cancer published in 2018 (box 1).2 It found no difference between one-time PSA screening and standard practice in prostate cancer mortality but found an increase in the detection of low risk prostate cancer after a median follow-up of 10 years.

 

[Michael Scally MD]

[OA] Low Testosterone and Prostate Cancer: Is the Protection Real?

Further, while not statistically significant, low serum free testosterone was associated with an increased risk of high-grade prostate cancer. Interestingly, in the presentation of these data at the National Cancer Research Institute Cancer Conference, the authors reported this risk to be statistically significant (OR = 1.65, 95% CI: 1.04–2.63). In patients with known prostate cancer, low testosterone levels have been associated with poorer oncologic outcomes among patients newly diagnosed with prostate cancer, those on active surveillance, and those treated with radical prostatectomy.

That low levels of testosterone would be associated with decreased risk of any prostate cancer diagnosis, but an increased risk of high-grade prostate cancer diagnosis, supports a detection bias-based interpretation of these data.

In this manuscript, Watts et al. [4] add to the growing literature supporting the saturation model, first proposed by Morgentaler and Traish [8]. Following its description, subsequent work demonstrated that hypogonadal men with total testosterone >250 ng/dl have an increase in PSA level following testosterone therapy while those with higher baseline levels of testosterone do not, thereby providing clinical support for the hypothesis that prostatic androgen receptors may become saturated.

The lack of a dose-response relationship in this analysis by Watts et al. further supports this saturation model, demonstrating that moving from the 2nd to 10th decile of testosterone concentration appears to have little effect on prostate cancer risk.

Finally, while Watts et al. provide interesting epidemiologic insights into prostate carcinogenesis and the relationship between baseline testosterone levels and prostate cancer risk, these data do not improve our ability to counsel patients or guide therapy today.

First, without controlling for detection bias, it is difficult to determine if patients with low baseline testosterone truly have a decreased risk of developing prostate cancer.

Second, and perhaps most importantly, these data do not provide guidance regarding how such risk may be modified by testosterone therapy. Prior analyses including men with laboratory confirmed low testosterone levels and recent PSA testing have demonstrated no increased risk of subsequent prostate cancer diagnosis for those receiving testosterone therapy [9, 10].

Wallis CJD, Krakowsky Y, Finelli A. Low Testosterone and Prostate Cancer: Is the Protection Real? Eur Urol 2018. https://www.europeanurology.com/article/S0302-2838(18)30616-X/fulltext

 

[Michael Scally MD]

[OA] Ilic D, Djulbegovic M, Jung JH, et al. Prostate cancer screening with prostate-specific antigen (PSA) test: a systematic review and meta-analysis. BMJ 2018;362. http://www.bmj.com/content/362/bmj.k3519.abstract

Objective To investigate the efficacy and safety of prostate-specific antigen (PSA) testing to screen for prostate cancer.

Design Systematic review and meta-analysis.

Data sources Electronic search of Cochrane Central Register of Controlled Trials, Web of Science, Embase, Scopus, OpenGrey, LILACS, and Medline, and search of scientific meeting abstracts and trial registers to April 2018.

Eligibility criteria for selecting studies Randomised controlled trials comparing PSA screening with usual care in men without a diagnosis of prostate cancer.

Data extraction At least two reviewers screened studies, extracted data, and assessed the quality of eligible studies. A parallel guideline committee (BMJ Rapid Recommendation) provided input on the design and interpretation of the systematic review, including selection of outcomes important to patients.

We used a random effects model to obtain pooled incidence rate ratios (IRR) and, when feasible, conducted subgroup analyses (defined a priori) based on age, frequency of screening, family history, ethnicity, and socioeconomic level, as well as a sensitivity analysis based on the risk of bias. The quality of the evidence was assessed with the GRADE approach.

Results Five randomised controlled trials, enrolling 721 718 men, were included. Studies varied with respect to screening frequency and intervals, PSA thresholds for biopsy, and risk of bias.

When considering the whole body of evidence, screening probably has no effect on all-cause mortality (IRR 0.99, 95% CI 0.98 to 1.01; moderate certainty) and may have no effect on prostate-specific mortality (IRR 0.96, 0.85 to 1.08; low certainty).

Sensitivity analysis of studies at lower risk of bias (n=1) also demonstrates that screening seems to have no effect on all-cause mortality (IRR 1.0, 0.98 to 1.02; moderate certainty) but may have a small effect on prostate-specific mortality (IRR 0.79, 0.69 to 0.91; moderate certainty). This corresponds to one less death from prostate cancer per 1000 men screened over 10 years. Direct comparative data on biopsy and treatment related complications from the included trials were limited.

Using modelling, we estimated that for every 1000 men screened, approximately 1, 3, and 25 more men would be hospitalised for sepsis, require pads for urinary incontinence, and report erectile dysfunction, respectively.

Conclusions At best, screening for prostate cancer leads to a small reduction in disease-specific mortality over 10 years but has does not affect overall mortality. Clinicians and patients considering PSA based screening need to weigh these benefits against the potential short and long term harms of screening, including complications from biopsies and subsequent treatment, as well as the risk of overdiagnosis and overtreatment.

 

[Michael Scally MD]

Teeling F, Raison MN, Shabbir MM, Yap MT, Dasgupta PP, Ahmed MK. Testosterone therapy for high-risk prostate cancer survivors: a systematic review and meta-analysis. Urology 2018. https://www.goldjournal.net/article/S0090-4295(18)30993-2/abstract

A systematic review and meta-analysis was performed to determine the relationship between testosterone therapy and risk of recurrence in testosterone-deficient survivors of curatively treated high-risk prostate cancer. Primary outcome was the risk of biochemical recurrence (BCR) in 109 high-risk patients in 13 included studies (1997-2017). Biochemical and symptomatic effects of therapy were also reviewed. The BCR rate was 0.00 (0.00-0.05), lower than the expected rate for high-risk prostate cancer survivors, suggesting that testosterone therapy may not increase their BCR risk. However, this is uncertain as the available evidence is of very low quality. Testosterone therapy remains investigational in this group.

 

[Michael Scally MD]

Neuzillet Y, Raynaud J-P, Dreyfus J-F, et al. Aggressiveness of Localized Prostate Cancer: the Key Value of Testosterone Deficiency Evaluated by Both Total and Bioavailable Testosterone: AndroCan Study Results. Hormones and Cancer 2018. Aggressiveness of Localized Prostate Cancer: the Key Value of Testosterone Deficiency Evaluated by Both Total and Bioavailable Testosterone: AndroCan Study Results

Failure rates after first-line treatment of localized prostate cancer (PCa) treatment remain high. Improvements to patient selection and identification of at-risk patients are central to reducing mortality. We aimed to determine if cancer aggressiveness correlates with androgen levels in patients undergoing radical prostatectomy for localized PCa.

We performed a prospective, multicenter cohort study between June 2013 and June 2016, involving men with localized PCa scheduled to undergo radical prostatectomy. Clinical and hormonal patient data (testosterone deficiency, defined by total testosterone (TT) levels < 300 ng/dL and/or bioavailable testosterone (BT) levels < 80 ng/dL) were prospectively collected, along with pathological assessment of preoperative biopsy and subsequent radical prostatectomy specimens, using predominant Gleason pattern (prdGP) 3/4 grading.

Of 1343 patients analyzed, 912 (68%) had prdGP3 PCa and 431 (32%) had high-grade (prdGP4, i.e., ISUP ≥ 3) disease on prostatectomy specimens. Only moderate concordance in prdGP scores between prostate biopsies and prostatectomy specimens was found.

Compared with patients with prdGP3 tumors (i.e., ISUP ≤ 2), significantly more patients with prdGP4 cancers had demonstrable hypogonadism, characterized either by BT levels (17.4% vs. 10.7%, p < 0.001) or TT levels (14.2% vs. 9.7%, p = 0.020). BT levels were also lower in patients with prdGP4 tumors compared to those with prdGP3 disease.

Testosterone deficiency (defined by TT and/or BT levels) was independently associated with higher PCa aggressiveness. BT is a predictive factor for prdGP4 disease, and evaluating both TT and BT to define hypogonadism is valuable in preoperative assessment of PCa (AndroCan Trial: NCT02235142).

 

[Michael Scally MD]

[OA] Look and You Will Find It: Practical Considerations for Improving Multidisciplinary Management of Androgen-Deprivation Therapy-Induced Cardiometabolic Toxicity

The potential adverse metabolic effects of various cancer therapies and their contribution to cardiovascular injury and disease have received comparatively less attention. In the accompanying clinical review, Gupta et al have addressed the underappreciated cardiometabolic toxicities of androgen-deprivation therapy (ADT), including novel agents, in prostate cancer. http://ascopubs.org/doi/10.1200/JOP.18.00178

Conventional ADT that results in lowering total serum testosterone to less than 50 ng/dL is the mainstay of treatment for advanced prostate cancer with about 600,000 men in the United States currently receiving ADT.

However, despite demonstrated efficacy, conventional ADT causes multiple detrimental metabolic and physical adverse effects, including muscle wasting (atrophy), decreased lean body mass (sarcopenia), increased body fat mass (obesity), and increased insulin resistance, which lead to a 44% increased risk of new onset type 2 diabetes and 16% risk of new ischemic heart disease. As Gupta et al describe in their review, novel ADT agents (ie, enzalutamide, abiraterone, and apalutamide) may exacerbate these adverse effects.

Khouri MG, Harrison MR. Look and You Will Find It: Practical Considerations for Improving Multidisciplinary Management of Androgen-Deprivation Therapy-Induced Cardiometabolic Toxicity. J Oncol Pract 2018;14:591-3. http://ascopubs.org/doi/10.1200/JOP.18.00543

 

[Michael Scally MD]

[OA] Cardiovascular and Metabolic Effects of Androgen-Deprivation Therapy for Prostate Cancer

Androgen-deprivation therapy (ADT) entails lowering serum testosterone levels to castrate levels and forms a cornerstone of the management of hormone-sensitive advanced prostate cancer; however, the benefit of ADT is partially offset by its detrimental metabolic and cardiovascular adverse effects.

ADT decreases insulin sensitivity while promoting dyslipidemia and sarcopenic obesity, which leads to an increased risk of cardiovascular morbidity and potentially mortality. The risk seems to be highest in elderly patients who have had recent cardiovascular events before starting ADT.

It is prudent to engage in an individualized risk-benefit discussion and develop a cohesive multidisciplinary management plan to medically optimize and closely observe these patients before and during treatment with ADT.

Gupta D, Lee Chuy K, Yang JC, Bates M, Lombardo M, Steingart RM. Cardiovascular and Metabolic Effects of Androgen-Deprivation Therapy for Prostate Cancer. J Oncol Pract 2018;14:580-7. http://ascopubs.org/doi/10.1200/JOP.18.00178

 

[MR10X]

i had ADT and i was down to 32 on TT.If i had to do it again i wouldnt have done the ADT and just done the seeds and radiation therapy. that was 6 years ago and my PSA was 0.1 on my last blood work.

 

[Michael Scally MD]

A Nomogram for Testosterone Recovery Following Combined Androgen Deprivation and Radiation Therapy for Prostate Cancer

PURPOSE: Testosterone recovery (TR) after androgen deprivation therapy (ADT) and radiation therapy (RT) is not well characterized. We studied TR in men who received RT and either short-term (ST) or long-term (LT) ADT and aimed to create a nomogram to predict TR.

METHODS AND MATERIALS: We identified consecutive localized PC patients treated with ADT-RT at two academic medical centers from 1/2011-10/2016 with documented baseline testosterone (T). TR was time from last ADT injection to T normalization. The Kaplan-Meier method was used to estimate time to TR. Cox proportional hazards models identified TR predictors. A nomogram was trained with site one and externally validated with site two.

RESULTS: 340 patients were included. 69.7% received STADT, median duration 6 months; 30.3% received LTADT, median duration 24.3 months. Median follow-up was 26.7 months. Median time for TR was 17.2 months for STADT and 24.0 months for LTADT patients (p = 0.004). The 2-year cumulative incidence of TR was 53.1% after LTADT vs 65.7% after STADT (p=0.004).

On multivariate analysis, shorter duration ADT (HR = 0.96, p = 0.004), higher pre-treatment T (HR = 1.004, p<0.001), and lower BMI (HR = 0.95, p = 0.002) were associated with shorter time to TR. Older age (HR = 0.97, p = 0.09) and white race (HR = 0.67, p = 0.06) trended as longer TR predictors. A nomogram was generated to predict probability of TR at 1, 2, and 3 years. The c-index was 0.71 (95%CI 0.64-0.78) for the validation cohort.

CONCLUSIONS: In this population of localized PC patients, TR following ADT-RT was variable. Using baseline T, ADT duration, BMI, age, and race, a predictive nomogram can estimate the likelihood of TR.

Spiegel DY, Hong JC, Oyekunle T, et al. A Nomogram for Testosterone Recovery Following Combined Androgen Deprivation and Radiation Therapy for Prostate Cancer. International journal of radiation oncology, biology, physics 2018. https://www.redjournal.org/article/S0360-3016(18)33954-3/pdf

 

[MR10X]

I went through that..4 months of ADT and 25 radiation treatments. My TT was 32 after all that. I did 2 cycles of HCG then Clomid and Nolvadex now my TT is in the normal range again

 

[Michael Scally MD]

Kasivisvanathan V, Rannikko AS, Borghi M, et al. MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis. New England Journal of Medicine 2018;378:1767-77. NEJM - Error

BACKGROUND - Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography–guided biopsy for prostate-cancer detection in men with a raised prostate-specific antigen level who have not undergone biopsy. However, comparative evidence is limited.

METHODS - In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography–guided biopsy. Men in the MRI-targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10-to-12–core, transrectal ultrasonography–guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer.

RESULTS - A total of 500 men underwent randomization. In the MRI-targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI-targeted biopsy group, as compared with 64 of 248 (26%) in the standard-biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI-targeted biopsy group than in the standard-biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, −13 percentage points; 95% CI, −19 to −7; P<0.001).

CONCLUSIONS - The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography–guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously.

 

[Michael Scally MD]

Rouvière O, Puech P, Renard-Penna R, et al. Use of prostate systematic and targeted biopsy on the basis of multiparametric MRI in biopsy-naive patients (MRI-FIRST): a prospective, multicentre, paired diagnostic study. The Lancet Oncology. Redirecting

Background - Whether multiparametric MRI improves the detection of clinically significant prostate cancer and avoids the need for systematic biopsy in biopsy-naive patients remains controversial. We aimed to investigate whether using this approach before biopsy would improve detection of clinically significant prostate cancer in biopsy-naive patients.

Methods - In this prospective, multicentre, paired diagnostic study, done at 16 centres in France, we enrolled patients aged 18–75 years with prostate-specific antigen concentrations of 20 ng/mL or less, and with stage T2c or lower prostate cancer. Eligible patients had been referred for prostate multiparametric MRI before a first set of prostate biopsies, with a planned interval of less than 3 months between MRI and biopsies. An operator masked to multiparametric MRI results did a systematic biopsy by obtaining 12 systematic cores and up to two cores targeting hypoechoic lesions. In the same patient, another operator targeted up to two lesions seen on MRI with a Likert score of 3 or higher (three cores per lesion) using targeted biopsy based on multiparametric MRI findings. Patients with negative multiparametric MRI (Likert score ≤2) had systematic biopsy only. The primary outcome was the detection of clinically significant prostate cancer of International Society of Urological Pathology grade group 2 or higher (csPCa-A), analysed in all patients who received both systematic and targeted biopsies and whose results from both were available for pathological central review, including patients who had protocol deviations. This study is registered with ClinicalTrials.gov, number NCT02485379, and is closed to new participants.

Findings - Between July 15, 2015, and Aug 11, 2016, we enrolled 275 patients. 24 (9%) were excluded from the analysis. 53 (21%) of 251 analysed patients had negative (Likert ≤2) multiparametric MRI. csPCa-A was detected in 94 (37%) of 251 patients. 13 (14%) of these 94 patients were diagnosed by systematic biopsy only, 19 (20%) by targeted biopsy only, and 62 (66%) by both techniques. Detection of csPCa-A by systematic biopsy (29·9%, 95% CI 24·3–36·0) and targeted biopsy (32·3%, 26·5–38·4) did not differ significantly (p=0·38). csPCa-A would have been missed in 5·2% (95% CI 2·8–8·7) of patients had systematic biopsy not been done, and in 7·6% (4·6–11·6) of patients had targeted biopsy not been done. Four grade 3 post-biopsy adverse events were reported (3 cases of prostatitis, and 1 case of urinary retention with haematuria).

Interpretation - There was no difference between systematic biopsy and targeted biopsy in the detection of ISUP grade group 2 or higher prostate cancer; however, this detection was improved by combining both techniques and both techniques showed substantial added value. Thus, obtaining a multiparametric MRI before biopsy in biopsy-naive patients can improve the detection of clinically significant prostate cancer but does not seem to avoid the need for systematic biopsy.

 

[Michael Scally MD]

[OA] van der Leest M, Cornel E, Israël B, et al. Head-to-head Comparison of Transrectal Ultrasound-guided Prostate Biopsy Versus Multiparametric Prostate Resonance Imaging with Subsequent Magnetic Resonance-guided Biopsy in Biopsy-naïve Men with Elevated Prostate-specific Antigen: A Large Prospective Multicenter Clinical Study. European Urology. Redirecting

Background - There is growing interest to implement multiparametric magnetic resonance imaging (mpMRI) and MR-guided biopsy (MRGB) for biopsy-naïve men with suspected prostate cancer.

Objective - Primary objective was to compare and evaluate an MRI pathway and a transrectal ultrasound-guided biopsy (TRUSGB) pathway in biopsy-naïve men with prostate-specific antigen levels of ≥3 ng/ml.

Design, setting, and population - A prospective, multicenter, powered, comparative effectiveness study included 626 biopsy-naïve patients (from February 2015 to February 2018).

Intervention - All patients underwent prebiopsy mpMRI followed by systematic TRUSGB. Men with suspicious lesions on mpMRI also underwent MRGB prior to TRUSGB. MRGB was performed using the in-bore approach.

Outcome measurements and statistical analysis - Clinically significant prostate cancer (csPCa) was defined as grade group ≥2 (Gleason score ≥3 + 4) in any core. The main secondary objectives were the number of men who could avoid biopsy after nonsuspicious mpMRI, the number of biopsy cores taken, and oncologic follow-up. Differences in proportions were tested using McNemar's test with adjusted Wald confidence intervals for differences of proportions with matched pairs.

Results and limitations - The MRI pathway detected csPCa in 159/626 (25%) patients and insignificant prostate cancer (insignPCa) in 88/626 patients (14%). TRUSGB detected csPCa in 146/626 patients (23%) and insignPCa in 155/626 patients (25%). Relative sensitivity of the MRI pathway versus the TRUSGB pathway was 1.09 for csPCa (p = 0.17) and 0.57 for insignPCa (p < 0.0001). The total number of biopsy cores reduced from 7512 to 849 (–89%). The MRI pathway enabled biopsy avoidance in 309/626 (49%) patients due to nonsuspicious mpMRI. Immediate TRUSGB detected csPCa in only 3% (10/309) of these patients, increasing to 4% (13/309) with 1-yr follow-up. At the same time, TRUSGB would overdetect insignPCa in 20% (63/309). “Focal saturation” by four additional perilesional cores to MRGB improved the detection of csPCa in 21/317 (7%) patients. Compared with the literature, our proportion of nonsuspicious mpMRI cases is significantly higher (27–36% vs 49%) and that of equivocal cases is lower (15–28% vs 6%). This is probably due to the high-quality standard in this study. Therefore, a limitation is the duplication of these results in less experienced centers.

Conclusions - In biopsy-naïve men, the MRI pathway compared with the TRUSGB pathway results in an identical detection rate of csPCa, with significantly fewer insignPCa cases. In this high-quality standard study, almost half of men have nonsuspicious MRI, which is higher compared with other studies. Not performing TRUS biopsy is at the cost of missing csPCa only in 4%.

Patient summary - We compared magnetic resonance imaging (MRI) with MRI-guided biopsy against standard transrectal ultrasound biopsy for the diagnosis of prostate cancer in biopsy-naïve men. Our results show that patients can benefit from MRI because biopsy may be omitted in half of men, and fewer indolent cancers are detected, without compromising the detection of harmful disease. Men also need fewer needles to make a diagnosis.

 

[MR10X]

maby i got lucky but had the TRUSBG with 12 samples taken and it wasnt painful at all..my PSA was 11 before biopsy. My biopsy came out gleason 8

 

[DTdr2]

Dr. Scally, what are your thoughts on INO in regards to their prostate treatment. I'm a proud shareholder based on their pipeline, but really interested in prostate studies. At the last CC it appears they will be announcing a partner pretty soon.
INO-5150 - Immuno-Oncology News

 

[Michael Scally MD]