Salvage partial gland ablation for recurrent prostate cancer following primary partial gland ablation: Functional and oncological outcomes

Introduction and ObjectivePartial gland ablation (PGA) for localised prostate cancer (CaP) aims to eradicate clinically significant tumours while preserving healthy tissue, thereby decreasing the likelihood of side effects compared to whole-gland approaches. Although salvage radical prostatectomy (sRP) is a well-described salvage option in cases of PGA failure, the evidence supporting salvage PGA (sPGA) is limited. We hereby report the oncologic and functional outcomes of patients treated with sPGA following initial treatment with primary PGA (pPGA).MethodsWe describe the findings of a retrospective review of patients who had a CaP recurrence after pPGA and then underwent sPGA, at 3 medical centers in Ontario, Canada, between 2005 and 2017. Oncological outcomes following sPGA were assessed for biochemical recurrence (BCR) and biopsy-proven recurrence (BPR). Functional outcomes were described using the international prostate symptom score (IPSS), international index of erectile function (IIEF), and rates of urinary incontinence (use of >1 pad/day).ResultsWe identified 25 patients who underwent sPGA following pPGA (hemiablation in 48% and zonal ablation in 52% of the patients). The median length of time was 16.8 months (interquartile range [IQR] 14.0–19.1) from pPGA to sPGA and 47.06 months (IQR 19.9–171.3) from pPGA to date of last follow up. High intensity focused ultrasound (HIFU) was the only modality used in all patients. At baseline, the median age was 65 years (IQR 52–77) and median prostate specific antigen (PSA) level was 7.46 ng/mL (IQR 1–25). The median time from pPGA to BPR was 12.7 months (IQR 5.19–36). At BPR following pPGA, 4 patients (17%) had CaP grade group (GG) 1, 10 patients (42%) had GG2, 6 patients (25%) had GG3, and 4 patients (17%) had GG4 disease, with a median PSA of 3.58 ng/mL (IQR 0.67–19). The median length of follow up after sPGA was 27.3 months (IQR 14.5–86.3). Following sPGA, 13/25 patients (52%) had BCR with median time to recurrence of 14 months (IQR 2.5–82.15), with a recurrence-free survival of 24.5 months (95% confidence interval: 15.3–not reached). Of those 13 patients, 4 were managed with sRP, 4 were managed with salvage radiotherapy, 3 were managed with androgen-deprivation therapy, 1 had a third PGA with HIFU, and 1 was managed with active surveillance. The mean change from baseline to last follow up in IPSS and IIEF scores was +1.3 (P = 0.66) and –2.3 (P = 0.32), respectively. Urinary incontinence was reported by 9% of patients at baseline, with only one additional patient developing incontinence following sPGA.ConclusionOur present study demonstrates that after a median follow-up of 27 months, sPGA for recurrent CaP following pPGA provides disease control in up to 50% of patients with nonsignificant detrimental effects on functional outcomes. Appropriate patient selection and adequate staging are important to consider before offering PGA to patients.     

The prognosis and the impact of radiotherapy in clinically regional lymph node-positive prostate cancer: Which patients are candidates for local therapy with radiation?

BackgroundThis study aimed to identify the prognostic and predictive factors of local radiotherapy in clinically regional lymph node-positive prostate cancer.Patients and MethodsThis study includes patients who were newly diagnosed with regional lymph node-positive prostate cancer between 2008 and 2017. We investigated the prognostic value of clinicopathological parameters for progression-free survival (PFS) and overall survival (OS) as well as the differential prognostic impact of radiotherapy by subgroup analysis.ResultsAmong the 93 men enrolled as patients, 48 (51.6 %) were treated with radiotherapy. The biopsy positive core rate and biopsy Gleason score were associated with PFS, and the number of lymph node metastases was associated with both PFS and OS. Patients who underwent radiotherapy showed better PFS and OS. High-risk features (at least 2 criteria among ≥75% biopsy positive core rate, Gleason score ≥9, and ≥2 positive lymph nodes) were especially associated with improved outcomes after undergoing radiotherapy.ConclusionWe identified prognostic factors for clinically regional lymph node-positive prostate cancer and showed the benefits of local radiation therapy. Patients with high-risk features may be especially suitable candidates for radiotherapy.     

3.0 T multiparametric prostate MRI using pelvic phased-array coil: Utility for tumor detection prior to biopsy

ObjectiveTo evaluate the role of multiparametric magnetic resonance imaging (MRI) performed in men without a biopsy-proven diagnosis of prostate cancer using follow-up biopsy as the reference standard.Materials and methodsForty-two patients without biopsy-proven cancer and who underwent MRI were included. In all patients, MRI was performed at 3T using a pelvic phased-array coil and included T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast-enhanced imaging. Thirteen had undergone no previous biopsy, and 29 had undergone at least 1 previous negative biopsy. All patients underwent prostate biopsy following MRI. Two fellowship-trained radiologists in consensus reviewed all cases and categorized each lobe as positive or negative for tumor. These interpretations were correlated with findings on post-MRI biopsy.ResultsFollow-up biopsy was positive in 23 lobes in 15 patients (36% of study cohort). On a per-patient basis, MRI had a sensitivity of 100%, specificity of 74%, positive predictive value (PPV) of 68%, and negative predictive value (NPV) of 100%. On a per-lobe basis, MRI had a sensitivity of 65%, specificity of 84%, PPV of 60%, and NPV of 86%. There was a nearly significant association between Gleason score and tumor detection on MRI (P = 0.072).ConclusionsIn our sample, MRI had 100% sensitivity in predicting the presence of tumor on subsequent biopsy on a per-patient basis, suggesting a possible role for MRI in selecting patients with an elevated prostatic specific antigen (PSA) to undergo prostate biopsy. However, MRI had weaker specificity for prediction of a subsequent positive biopsy, as well as weaker sensitivity for tumor on a per-lobe basis, indicating that in patients with a positive MRI result, tissue sampling remains necessary for confirmation of the diagnosis as well as for treatment planning.     

An algorithm for managing the failure of external beam radiotherapy in prostate cancer

OBJECTIVE: To present a management algorithm for men with prostate cancer recurring after external beam radiotherapy (EBRT), based on a review of published reports, to assist clinicians in identifying men who are suitable for salvage therapy and to help them to decide which type of salvage treatment is most likely to confer the desired outcome with the minimum of harm. METHODS: Men with radiorecurrent prostate cancer require special consideration; they tend to be older, have more comorbidity and have worse disease than their contemporaries having primary treatment. Salvage treatment is compromised by the irradiated pelvis, resulting in increased treatment toxicity. Using the Pubmed database and reference lists of key articles, we identified studies relating to the management of radiorecurrent prostate cancer; the findings were incorporated into a management algorithm and summary table of treatments. RESULTS: The American Society for Therapeutic Radiology and Oncology criteria, which define biochemical failure has now been superseded by the Phoenix definition (nadir prostate-specific antigen [PSA] plus 2 ng/mL). Biochemical follow-up after EBRT should be 3-monthly until the PSA level has reached a stable nadir after withdrawing androgen suppression. Contrast-enhanced dynamic magnetic resonance imaging (MRI) is an accurate tool and can be used for both the diagnosis and staging of patients with prostate cancer, in conjunction with prostate biopsies. Prostate biopsies should only be considered >2 years after EBRT to avoid false-positive results. In addition to MRI, high-risk cases being considered for salvage therapy should be considered for laparoscopic lymph-node dissection to exclude micrometastases. Deferred androgen suppression, laparoscopic or open radical prostatectomy, cryotherapy and high-intensity focused ultrasound all seem reasonable salvage treatment approaches. CONCLUSION: Through improved methods of detection, including frequent PSA measurements, modern imaging and carefully obtained biopsies, those with radiorecurrent disease can be identified before their disease has spread. Rigorous staging will exclude those with micrometastases. The minimally invasive salvage therapies seem to offer an advantage over salvage surgery to patients in whom the benefits and harms are so finely balanced.     

Randomized Study of Systematic Biopsy Versus Magnetic Resonance Imaging and Targeted and Systematic Biopsy in Men on Active Surveillance (ASIST): 2-year Postbiopsy Follow-up

BackgroundThe initial report from the ASIST trial showed little benefit from targeted biopsy for men on active surveillance (AS) for prostate cancer. Data after 2-yr follow-up are now available for analysis.ObjectiveTo determine if there was a difference in the AS failure rate in a 2-yr follow-up period among men undergoing magnetic resonance imaging (MRI) before initial confirmatory biopsy (CBx) compared to those who did not.Design, setting, and participantsThis is the 2-yr post-CBx follow-up for the ASIST trial, a prospective, randomized, multicenter, open-label study for men with Gleason grade group (GG) 1 cancer eligible for AS. Patients were randomized to CBx with 12-core systematic sampling or MRI with systematic and targeted sampling.Outcome measurements and statistical analysisPatients with GG ≤ 1 on CBx were followed for 2 yr and had MRI and biopsy at that time point. Patients failed AS if they were no longer under AS because of grade progression, clinical progression, subject choice, clinical judgment, treatment, or lost to follow-up. Clinically significant cancer (CSC) was defined as GG ≥ 2.Results and limitationsIn total, 259 men underwent CBx, 132 in the non-MRI and 127 in the MRI arm. After biopsy, 101 men in the non-MRI arm (76%) and 98 in the MRI arm (77%) continued AS. There were fewer men with AS failures in the MRI (19/98, 19%) compared to the non-MRI group (35/101, 35%; p = 0.017). At 2-yr biopsy there were fewer men with CSC in the MRI arm (9.9%, 8/81) than in the non-MRI arm (23%, 17/75; p = 0.048). Significant differences in AS failure rates were detected across the three centers in the MRI arm only (4.2% [2/48] vs 17% [4/24] vs 27% [7/26]; p = 0.019).ConclusionsBaseline MRI before CBx during AS results in 50% fewer AS failures and less grade progression over 2 yr. The center where MRI and targeted biopsy is performed may influence AS failure rates.Patient summaryThe ASIST trial randomized 273 men on active surveillance with low-grade prostate cancer diagnosed within the last year to systematic biopsy or magnetic resonance imaging (MRI) with systematic and targeted biopsy. The initial report showed little benefit from targeted biopsy. However, after 2 yr of follow-up we found that baseline MRI before confirmatory biopsy resulted in 50% fewer failures of surveillance and less progression to higher-grade cancer. This confirms the value of MRI in men on surveillance.This study is registered at ClinicalTrials.gov (NCT01354171).     

Initial experience with electronic tracking of specific tumor sites in men undergoing active surveillance of prostate cancer

ObjectivesTargeted biopsy, using magnetic resonance (MR)-ultrasound (US) fusion, may allow tracking of specific cancer sites in the prostate. We aimed to evaluate the initial use of the technique to follow tumor sites in men on active surveillance of prostate cancer.Methods and materialsA total of 53 men with prostate cancer (all T1c category) underwent rebiopsy of 74 positive biopsy sites, which were tracked and targeted using the Artemis MR-US fusion device (Eigen, Grass Valley, CA) from March 2010 through January 2013. The initial biopsy included 12 cores from a standard template (mapped by software) and directed biopsies from regions of interest seen on MR imaging (MRI). In the repeat biopsy, samples were taken from sites containing cancer at the initial biopsy. Outcomes of interest at second MR-US biopsy included (a) presence of any cancer and (b) presence of clinically significant cancer.ResultsAll cancers on initial biopsy had either Gleason score 3+3 = 6 (n = 63) or 3+4 = 7 (n = 11). At initial biopsy, 23 cancers were within an MRI target, and 51 were found on systematic biopsy. Cancer detection rate on repeat biopsy (29/74, 39%) was independent of Gleason score on initial biopsy (P = not significant) but directly related to initial cancer core length (P<0.02). Repeat sampling of cancerous sites within MRI targets was more likely to show cancer than resampling of tumorous systematic sites (61% vs. 29%, P = 0.005). When initial cancer core length was≥4 mm within an MRI target, more than 80% (5/6) of follow-up tracking biopsies were positive. An increase of Gleason score was uncommon (9/74, 12%).ConclusionsMonitoring of specific prostate cancer–containing sites may be achieved in some men using an electronic tracking system. The chances of finding tumor on repeat specific-site sampling was directly related to the length of tumor in the initial biopsy core and presence of tumor within an MRI target; upgrading of Gleason score was uncommon. Further research is required to evaluate the potential utility of site-specific biopsy tracking for patients with prostate cancer on active surveillance.     

Cancer-specific outcomes for prostate cancer patients who had prebiopsy prostate MRI

PurposeWe characterized population-level cancer-specific outcomes for prostate cancer patients based on use of prebiopsy prostate MRI.MethodsUsing SEER-Medicare claims, we identified men diagnosed with localized prostate cancer from 2010–2015 and prostate-specific antigen (PSA) < 20 ng/mL. Primary exposure was prebiopsy prostate MRI prior to diagnosis (i.e., CPT 72197 linked to urology-specific diagnosis). Outcomes included diagnosis of Grade Group 2+ disease on biopsy and proportion treated with prostatectomy. We assessed those treated with prostatectomy and evaluated association with prebiopsy MRI and grade concordance between biopsy and prostatectomy. We estimated adjusted odds ratios with multivariable regression after accounting for other factors (e.g., age, year, PSA, race/ethnicity).ResultsWe identified 48,574 patients, where 915 (1.9%) underwent prebiopsy MRI. Patients with prebiopsy MRI had more GG>2 cancer on biopsy (70.0% MRI vs. 62.8% no MRI) but lost significance after adjustment (OR 1.12, 95% CI 0.96–1.30). Patients with prebiopsy MRI were more likely to have prostatectomy (39.2% vs. 28.5%, adjusted OR 1.51, 95%CI 1.31–1.76). Downgrading from biopsy GG 3–5 to final GG 1–2 was less common after prebiopsy MRI (21.3% vs. 28.2% no MRI, P = 0.05) but not significant after adjustment (OR 0.74, 95% CI 0.51 – 1.08). Among 14,027 men with prostatectomy, accurate risk classification was not more likely with a prebiopsy MRI (48.0% no MRI vs. 49.6% prebiopsy MRI, P = 0.56).ConclusionDuring initial adoption, men with prebiopsy prostate MRI had marginally increased detection of significant cancer on biopsy and were more likely to be treated with prostatectomy. For those treated with prostatectomy, use of prebiopsy MRI was not associated with a greater likelihood of accurate risk classification or grade concordance between biopsy and final pathology results.     

Validation of the current eligibility criteria for focal therapy in men with localized prostate cancer and the role of MRI

Purpose

To validate current eligibility criteria for focal therapy (FT) in prostate cancer men undergoing radical prostatectomy (RP) and to assess the role of magnetic resonance imaging (MRI).

Methods

Retrospective analysis of 217 RP patients (2009–2016) with preoperative MRI (almost all in external institutions) and fulfillment of different FT eligibility criteria: unilateral tumor, clinical tumor stage ≤ cT2a, prostate volume ≤ 60 mL and either biopsy Gleason 3 + 3 or ≤ 3 + 4 and PSA ≤ 10 or ≤ 15 ng/mL. Multivariable logistic regression analyses (MVA) assessed the role of MRI to predict the presence of significant contralateral tumor or extracapsular extension (ECE), including seminal vesicle invasion. To quantify model accuracy, Receiver Operating Characteristics-derived area under the curve (AUC) was used.

Results

Of 217 patients fulfilling widest biopsy criteria and 113 fulfilling additional MRI criteria, 64 (29.7%) and 37 (32.7%) remained eligible for FT according to histopathological results. In MVA, fulfillment of MRI criteria reached independent predictor status for prediction of contralateral tumor but not for ECE. Addition of MRI resulted in AUC gain (57.5–64.6%). Sensitivity, specificity, PPV and NPV for MRI to predict contralateral tumor were: 41.8, 71.6, 70.9 and 42.6%, respectively. Virtually the same results were recorded for Gleason 3 + 3 and/or PSA ≤ 10 ng/mL.

Conclusions

Patient eligibility criteria for FT using biopsy criteria remained insufficient with respect to contralateral tumor disease. Although, MRI improves accuracy, it cannot safely exclude or minimize chance of significant cancer on contralateral prostate side. To date, stricter eligibility criteria are needed to provide more diagnostic reliability.

     

Medium Term Outcomes of Focal Cryoablation for Intermediate and High Risk Prostate Cancer: MRI and PSA are Not Predictive of Residual or Recurrent Disease

ObjectiveTo understand oncologic outcomes of focal cryoablation for prostate cancer and efficacy MRI and PSA to predict residual disease and recurrence.MethodsWe retrospectively analyzed patients who underwent focal cryotherapy at a single institution. Inclusion criteria included clinically localized biopsy-proven cancer that was clearly visible on MRI or ultrasound. The primary outcomes were failure-free survival (FFS) defined as no transition to radical, whole-gland or systemic therapy and biochemical recurrence (Phoenix PSA nadir +2 increases), and secondary outcomes included changes in the Gleason grade group (GG) and MRI findings.Results75 patients completed post cryotherapy biopsy with a median follow-up of 1.89 [IQR 1.19-2.77] years. Failure free survival was met by 96.2% of patients at 2 year follow up and of those who did not meet this outcome, 3 had metastasis, 1 had a salvage prostatectomy and 5 underwent radiation. On the treated side of the prostate, 7 (9.5%) of patients had residual ≥GG2 disease compared to 7 (9.5%) patients on the untreated side. Out of the 12 patients who had residual ≥GG2 disease at follow up biopsy (either on treated or untreated side of the prostate), 11 (91.7%) had PI-RADS 1-3 on follow up MRI. Using a multivariate cox proportional hazards model, Phoenix criteria for recurrence (PSA nadir +2) was not predictive for FFS.ConclusionsFocal cryotherapy is effective for treating focal lesions of prostate cancer, but patients require continued surveillance. MRI and PSA are not reflective of residual disease on follow up biopsy.     

Oncological outcomes of salvage radical prostatectomy for recurrent prostate cancer in the contemporary era: A multicenter retrospective study

BackgroundSalvage radical prostatectomy (sRP) historically yields poor functional outcomes and high complication rates. However, recent reports on robotic sRP show improved results.Our objectives were to evaluate sRP oncological outcomes and predictors of positive margins and biochemical recurrence (BCR).MethodsWe retrospectively collected data of sRP for recurrent prostate cancer after local nonsurgical treatment at 18 tertiary referral centers in United States, Australia and Europe, from 2000 to 2016. SM and BCR were evaluated in a univariate and multivariable analysis. Overall and cancer-specific survival were also assessed.ResultsWe included 414 cases, 63.5% of them performed after radiotherapy. Before sRP the majority of patients had biopsy Gleason score (GS) ≤7 (55.5%) and imaging negative or with prostatic bed involvement only (93.3%). Final pathology showed aggressive histology in 39.7% (GS ≥9 27.6%), with 52.9% having ≥pT3 disease and 16% pN+. SM was positive in 29.7%. Five years BCR-Free, cancer-specific survival and OS were 56.7%, 97.7% and 92.1%, respectively. On multivariable analysis pathological T (pT3a odds ratio [OR] 2.939, 95% confidence interval [CI] 1.469–5.879; ≥pT3b OR 2.428–95% CI 1.333–4.423) and N stage (pN1 OR 2.871, 95% CI 1.503–5.897) were independent predictors of positive margins. Pathological T stage ≥T3b (OR 2.348 95% CI 1.338–4.117) and GS (up to OR 7.183, 95% CI 1.906–27.068 for GS >8) were independent predictors for BCR. Limitations include the retrospective nature of the study and limited follow-up.ConclusionsIn a contemporary series, sRP showed promising oncological control in the medium term despite aggressive pathological features. BCR risk increased in case of locally advanced disease and higher GS. Future studies are needed to confirm our findings.     

Unilateral lesion detected on preoperative multiparametric magnetic resonance imaging and MRI/US fusion-guided prostate biopsy is not an appropriate indication for focal therapy in prostate cancer

PurposeThis study aimed to investigate if preoperative assessments of multiparametric magnetic resonance imaging (mpMRI) and Magnetic resonance imaging /ultrasound (MRI/US) fusion-guided prostate biopsy could be used to guide focal therapy for prostate cancer.Materials and MethodsA total of 101 prostate cancer patients undergoing radical prostatectomy were included. Preoperative findings included mpMRI and MRI/US fusion-guided prostate biopsy, while postoperative whole mount pathology was based on surgical specimen.ResultsOf the 101 patients preoperatively diagnosed with a unilateral tumor, postoperative whole mount pathology showed 73.27% were bilateral tumors, and 71.62% of bilateral lesions were clinically significant. Comparison between preoperative and postoperative findings, the correct rate of preoperative mpMRI on the lesion side (left or right) was only 20.79%. As for the Gleason score, the correct rate of preoperative MRI/US fusion-guided prostate pathology was 67.33%. Judging from postoperative whole mount pathology, 47.52% of patients had a unilateral clinically significant tumor, which is an indication for focal therapy.ConclusionPreoperative examinations of mpMRI and MRI/US fusion-guided prostate biopsy cannot be used to guide focal therapy for prostate cancer.     

Prostate Magnetic Resonance Imaging,with or Without Magnetic Resonance Imaging-targeted Biopsy,and Systematic Biopsy for Detecting Prostate Cancer: A Cochrane Systematic Review and Meta-analysis

ContextMagnetic resonance imaging (MRI), with or without MRI-targeted biopsy (MRI pathway), is an alternative test to systematic transrectal ultrasonography-guided biopsy in men suspected of having prostate cancer. At present, evidence on which test to use is insufficient to inform detailed evidence-based decision making.ObjectiveTo determine the diagnostic accuracy of the index tests MRI only, MRI-targeted biopsy, MRI pathway, and systematic biopsy, as compared with template-guided biopsy (reference standard), in detecting clinically significant prostate cancer, defined as International Society of Urological Pathology grade 2 or higher, in biopsy-naive men or those with a prior-negative biopsy (or mix of both).Evidence acquisitionWe systematically searched the literature and considered for inclusion any cross-sectional study if it investigated (1) one or more index tests verified by the reference standard, and (2) paired testing of the MRI pathway with systematic biopsy. Quality and certainty of evidence were assessed by the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and Grading of Recommendations Assessment, Development and Evaluation, respectively.Evidence synthesisAccuracy analyses: Using a baseline cancer prevalence of 30%, MRI pathway (sensitivity 0.72 [95% confidence interval {CI}: 0.60–0.82]; specificity 0.96 [0.94–0.98]; eight studies) may result in 216 (180–246) true positives, 28 (14–42) false positives, 672 (658–686) true negatives, and 84 (54–120) false negatives per 1000 men. Systematic biopsy (sensitivity 0.63 [0.19–0.93]; specificity 1.00 [0.91–1.00]; four studies) may result in 189 (57–279) true positives, 0 (0–63) false positives, 700 (637–700) true negatives, and 111 (21–243) false negatives per 1000 men. Agreement analyses: With a direct comparison of the MRI pathway with systematic biopsy concerning significant disease, we found pooled detection ratios of 1.05 (95% CI: 0.95–1.16; 20 studies) in biopsy-naive men and 1.44 (1.19–1.75; 10 studies) in men with a prior-negative biopsy. Concerning insignificant disease, we found detection ratios of 0.63 (95% CI: 0.54–0.74), and 0.62 (95% CI: 0.44–0.88), respectively.ConclusionsMRI pathway had the most favourable outcome in significant and insignificant prostate cancer detection compared with systematic biopsy. The certainty in our findings was reduced by study limitations.Patient summaryWe reviewed recent advances in prostate biopsy by magnetic resonance imaging (MRI) guidance and targeting for prostate cancer detection in comparison with standard diagnosis by systematic biopsies. The findings of this Cochrane review suggest that MRI pathway is better than systematic biopsies in making a correct diagnosis of clinically important prostate cancer and reducing redundant biopsies and the detection of unimportant cancers substantially. However, MRI pathway still misses some men with important prostate cancer. Therefore, further research in this area is important.     

Hormone therapy for radiorecurrent prostate cancer

Background

The management of patients who relapse after radical radiotherapy is a challenging problem for the multidisciplinary team. This group of men may have been considered ineligible or chosen not to be treated with an initial surgical approach as a result of high-risk features or significant comorbid conditions. It is important not to miss the opportunity for definitive local salvage therapies at this stage, and eligible patients should undergo careful restaging to determine their suitability for these approaches. For those men not suitable for local treatment, androgen deprivation therapy (ADT) remains an option.

Methods

Literature review of the evidence relating to the management of hormone therapy for radiorecurrent prostate cancer.

Results

Results from retrospective studies have shown that not all men with biochemical relapse will experience distant metastasis or a reduction in survival due to prostate cancer progression. Therefore, the timing of ADT commencement remains controversial. However, it would seem appropriate to offer immediate therapy to men with advanced disease or unfavourable prostate-specific antigen (PSA) kinetics at relapse. Patients with more favourable risk factors and PSA kinetics may be considered for watchful waiting and deferred ADT to avoid or delay the associated toxicities. Patients with non-metastatic disease can be given the option of castration-based therapy or an antiandrogen such as bicalutamide which may have potential advantages in maintenance of sexual function, physical capacity and bone mineral density but at the expense of an increase in gynaecomastia and mastalgia. Recent data suggest the burden of toxicity from ADT may be reduced by the use of intermittent hormone therapy without compromising survival in this group of patients with radiorecurrence.

Conclusions

Hormone therapy remains an option for men with radiorecurrent prostate cancer.     

Assessing the diagnostic performance of systematic freehand PrecisionPoint transperineal prostate biopsy: Comparison of observed outcomes to PBCG nomogram predictions

ObjectiveWe assessed the diagnostic performance of freehand systematic transperineal biopsy (fTPb) by using the Prostate Biopsy Collaborative Group (PBCG) nomogram, which is a contemporary update to the PCPT nomogram.MethodsFrom 1/2012 to 12/2018, fTPb was performed on consecutive men with clinical suspicion of prostate cancer. Patients included in this study had no previous diagnosis of prostate cancer, PSA between 2.5 ng/ml and 20 ng/ml, and underwent at least 12 core biopsies. In addition, those men who underwent pre-biopsy multiparametric magnetic resonance imaging of the prostate were considered separately from those without prebiopsy imaging. Biopsies were performed by a single urologist who developed the needle guidance device used in the procedure. Clinical and pathological data were collected retrospectively. We compared observed biopsy outcomes with those predicted by PBCG nomogram utilizing chi-square statistical analysis.ResultsSystematic fTPb (without pre-biopsy MRI) was performed in 301 men (median age 67, mean PSA 6.9 ng/mL). These men had a median of 20 biopsy cores. Clinically significant cancer (ISUP 2 or greater) was found in 33.9% of men. In men without pre-biopsy MRI, using PBCG Nomogram, we found no significant difference between the expected and observed number of clinically significant cancer (96 vs. 102; P = 0.09). An additional 73 men (median age 67, mean PSA 7.8 ng/ml) underwent pre-biopsy MRI imaging. The addition of MRI targets to systematic sampling resulted in a median of 25 cores. Clinically significant cancer was found in 49.3%. Using the PBCG Nomogram, in the men with pre-biopsy MRI we found clinically significant cancer in significantly more men than was expected by PBCG nomogram predictions (36 vs. 20; P = <0.01). There were no biopsy-related infectious complications.ConclusionThe fTPb technique is a promising method to sample the prostate which provides cancer detection that is comparable to that expected from systematic TRUS biopsy. We found that pre-biopsy mpMRI resulted in greater than expected detection of clinically significant cancer when utilizing this technique.     

The Role of Biopsy Core Number in Selecting Prostate Cancer Patients for Active Surveillance

Background

Studies offer wide variations in inclusion criteria for active surveillance (AS) in prostate cancer (PCa), but the role of the biopsy core number has not been thoroughly assessed.

Objective

To evaluate the impact of the biopsy core number on the risk of misclassification for AS eligibility.

Design, setting, and participants

: This prospective study included 411 men eligible for AS who fulfilled at least one of four of the criteria reported in the literature groupings among a screening cohort of 2917 patients.

Intervention

All patients underwent a 21-core biopsy with cores mapped by location and acted as controls of themselves for the analysis of biopsy core number (6-, 12- and 21-core schemes). Radical prostatectomy (RP) was performed in 297 men (72%).

Measurements

The number of included patients, PCa extent on biopsy, rate of unfavorable disease in RP specimens, and biochemical recurrence-free survival were compared as a function of (1) the different criteria groupings for AS and (2) the biopsy core number (6, 12, or 21).

Results and limitations

Of the 1104 patients with PCa, the proportion eligible for AS ranged from 22.5% to 35.4% based on AS criteria. In men who fulfilled AS criteria only in a 12-core strategy, tumor length and percentage of cancer involvement on biopsy were significantly greater than in those who fulfilled AS criteria in a 21-core scheme. The rate of unfavorable disease on RP specimens was also higher in the former group, from 28.6% to 35.9% relative to AS criteria (p = 0.014, 0.044, and 0.113 in groups 2, 3, and 4, respectively).

Conclusions

Men eligible for AS based on a 21-core strategy have cancers with a lower extent of disease on biopsies and a lower risk of unfavorable disease on RP specimens regardless of how AS criteria are defined, compared with men eligible in a 12-core scheme.     

Active surveillance for prostate cancer

Many men diagnosed with localized prostate cancer can postpone definitive treatment without raising their risk of metastasis or death from disease. Active surveillance (AS) is a method of monitoring select men, with the option of switching to active treatment upon signs of progression, thereby avoiding the well-known side-effects of surgery and radiotherapy. This review analyzes the data from long-running AS cohorts to determine the safety and efficacy of AS. We conducted a narrative review of recently published data, including 14 articles from 13 AS cohorts. The cohorts used varying inclusion criteria, with reported differences in clinical T stage and Gleason Score (Grade Group), among other features. Some studies (n=5) limited their cohorts to low-risk patients, while others (n=8) also included intermediate-risk patients. The heterogeneity of the cohorts produced mixed results, with the risk of prostate cancer metastasis ranging from 0.1–1.0% at 10 years and the risk of prostate cancer mortality ranging from 0–1.9% at 10 years. However, the majority of studies reported risks of less than 0.5% at 10 years for both metastasis and death. For most cohorts, half of men remained untreated for 5–10 years, with estimates ranging from 37% receiving active treatment in the Toronto cohort to 73% in the Prostate Cancer Research International AS (PRIAS) study. Current data do not support the use of negative magnetic resonance imaging (MRI) to avoid scheduled biopsy. Taken together, the data collected from these AS cohorts suggests that AS is a safe approach for men with low-grade prostate cancer and some men with intermediate risk disease. AS should be more broadly implemented for eligible patients to avoid the decreases in quality of life from undergoing active treatment. Studies expanding the inclusion criteria and further defining a subset of men with favorable intermediate-risk prostate cancer who might safely benefit from AS are needed to assess the long-term outcomes of using AS in intermediate-risk groups.     

Can quantitative analysis of multi-parametric MRI independently predict failure of focal salvage HIFU therapy in men with radio-recurrent prostate cancer?

ObjectivesFocal salvage HIFU is a feasible therapeutic option in some men who have recurrence after primary radiotherapy for prostate cancer. We aimed to determine if multi-parametric quantitative parameters, in addition to clinical factors, might have a role in independently predicting focal salvage HIFU outcomes.MethodsA retrospective registry analysis included 150 consecutive men who underwent focal salvage HIFU (Sonablate500) (2006-2015); 89 had mpMRI available. Metastatic disease was excluded by nodal assessment on pelvic MRI, a radioisotope bone-scan and/or choline or FDG PET/CT scan. All men had mpMRI and either transperineal template prostate mapping biopsy or targeted and systematic TRUS-biopsy. mpMRI included T2‐weighted, diffusion‐weighted and dynamic contrast‐enhancement. Pre-HIFU quantitative mpMRI data was obtained using Horos DICOM Viewer v3.3.5 for general MRI parameters and IB DCE v2.0 plug-in. Progression-free survival (PFS) was defined by biochemical failure and/or positive localized or distant imaging results and/or positive biopsy and/or systemic therapy and/or metastases/prostate cancer‐specific death. Potential predictors of PFS were analyzed by univariable and multivariable Cox-regression.ResultsMedian age at focal salvage HIFU was 71 years (interquartile range [IQR] 65–74.5) and median PSA pre-focal salvage treatment was 5.8ng/ml (3.8-8). Median follow-up was 35 months (23-47) and median time to failure was 15 months (7.8–24.3). D-Amico low, intermediate and high-risk disease was present in 1% (1/89), 40% (36/89) and 43% (38/89) prior to focal salvage HIFU (16% missing data). 56% (50/89) failed by the composite outcome. A total of 22 factors were evaluated on univariable and 8 factors on multivariable analysis. The following quantitative parameters were included: Ktrans, Kep, Ve, Vp, IS, rTTP and TTP. On univariable analysis, PSA, prostate volume at time of radiotherapy failure and Ve (median) value were predictors for failure. Ve represents extracellular fraction of the whole tissue volume. On multivariable analysis, only Ve (median) value remained as an independent predictor.ConclusionsOne pharmacokinetic quantitative parameter based on DCE sequences seems to independently predict failure following focal salvage HIFU for radio-recurrent prostate cancer. This likely relates to the tumor microenvironment producing heat-sinks which counter the heating effect of HIFU. Further validation in larger datasets and evaluating mechanisms to reduce heat-sinks are required.     

Sensitivity of multiparametric MRI and targeted biopsy for detection of adverse pathologies (Cribriform gleason pattern 4 and intraductal carcinoma): Correlation of detected and missed prostate cancer foci with whole mount histopathology

PurposeAccurate preoperative detection of prostate cancer (PCa) exhibiting “cribriform” morphology (intraductal carcinoma [IDC-P] or cribriform Gleason pattern 4 [CrP4]) is important as it is independently associated with a variety of adverse clinical outcomes. The sensitivity of multiparametric magnetic resonance imaging (mpMRI) in the detection of PCa exhibiting “cribriform” morphology remains controversial.Materials and MethodsA total of 117 eligible men with prospectively reported mpMRI who underwent in-bore MRI targeted biopsy followed by whole-mount radical prostatectomy (RP) were analyzed for lesion-level imaging-pathology correlation.ResultsOf the 206 PCa foci at RP (117 index and 89 non-index), 74% (152/206) were detected by mpMRI. Of the 54 tumors missed by mpMRI, most were non-index (98%, 53/54), grade group (GG) 1 (68%, 37/54) or GG 2 (26%, 14/54), with a median size of 1.0 cm (range, 0.7-1.5 cm), and non-cribriform morphology (96%, 52/54). Cribriform morphology was detected in 26% (53/206) of all tumors, and although targeted biopsies identified 96% (51/53) of these cancers, the cribriform component was depicted in only 45% (24/53). Of these, mpMRI detected all (100%, 44/44) index and 78% (7/9) of the non-index tumors. At univariable analysis, tumor size greater than 5 mm, % pattern 4 > 5%, cribriform morphology, zone (transition versus peripheral zone), and region (apex versus mid/base) were significantly associated with tumor visibility at mpMRI. At multivariable analysis, only tumor size, presence of any pattern 4, and peripheral zone remained significant predictors for visibility by mpMRI.ConclusionAt a lesion level, mpMRI offers high sensitivity for the detection of cribriform morphologies, however, the cribriform component is frequently missed by targeted biopsies. The MRI visibility is significantly associated with larger tumor size, presence of Gleason pattern 4, and peripheral zone location.     

A MODEL FOR THE NUMBER OF CORES PER PROSTATE BIOPSY BASED ON PATIENT AGE AND PROSTATE GLAND VOLUME

Purpose

The systematic sextant biopsy is currently the gold standard for the tissue diagnosis of prostate cancer. However, it is unknown whether this 6 core approach provides optimal sampling of all prostate glands in men of all ages. The goal of the current study was to determine the appropriate number of cores per prostate biopsy based on patient age and prostate gland volume.

Materials and Methods

Patient age and tumor volume doubling time were used to calculate life threatening, clinically significant tumor volumes at diagnosis for 5-year intervals of patient age. A mathematical model was created to determine the minimum number of cores necessary to identify these life threatening tumor volumes in prostate glands 10 to 80 cm.³ without detecting clinically insignificant cancers.

Results

Younger men and men with larger prostate glands require more than 6 cores to ensure the diagnosis of life threatening prostate cancer. These prostates are currently under sampled by sextant biopsy. In a select group of older men who require fewer than 6 cores sextant biopsy may over sample these prostates and lead to over treatment.

Conclusions

The standard sextant biopsy provides optimal sampling of only a minority of prostate glands. An approach to prostate biopsy based on patient age and prostate gland volume maximizes the detection of clinically significant prostate cancer.     

Risk of adverse pathology at prostatectomy in the era of MRI and targeted biopsies; rethinking active surveillance for intermediate risk prostate cancer patients

PurposeMen with intermediate risk (IR) prostate cancer (CaP) are often excluded from active surveillance (AS) due to higher rates of adverse pathology (AP). We determined our rate of AP in men who underwent multiparametric MRI (MpMRI) with combined biopsy (CB) consisting of targeted biopsy (TB) and systematic biopsy (SB) prior to radical prostatectomy (RP).MethodsA retrospective review was conducted of men with Gleason Grade Group (GG) 2 disease who underwent RP after SB alone or after preoperative MRI with CB. AP was defined as either pathologic stage T3a (AP ≥ T3a) or pathologic stage T3b (AP ≥ T3b) and/or GG upgrading. Rates of AP were determined for both groups and those who fit the National Comprehensive Cancer Network (NCCN) definition of favorable IR (FIR) or the low volume IR (LVIR) criteria. Multivariable logistic regression was used to determine predictive factors.ResultsThe overall rate of AP ≥ T3b was 21.2% in the SB group vs. 8.6% in the MRI with CB group, P = 0.006. This rate was lowered to 6.8% and 5.6% when men met the definition of NCCN FIR or LVIR, respectively. Suspicion for extraprostatic extension (EPE) (OR 7.65, 95% CI 1.77−33.09, P = 0.006) and positive cores of GG 2 on SB (OR 1.43, 95% CI 1.05−1.96, P = 0.023) were significant for predicting AP ≥ T3b.ConclusionsRates of AP at RP after MRI with CB are lower than studies prior to the adoption of this technology, suggesting that more men with IR disease may be considered for AS. However, increasing cores positive on SB and MRI findings suggestive of EPE remain unsafe.