Kareem Rayn

New therapies in nonmuscle invasive bladder cancer treatment

Introduction: Nonmuscle invasive bladder cancer (NMIBC) remains a very challenging disease to treat with high rates of recurrence and progression associated with current therapies. Recent technological and biological advances have led to the development of novel agents in NMIBC therapy. Methods: We reviewed existing literature as well as currently active and recently completed clinical trials in NMIBC by querying PubMed.gov and clinicaltrials.gov. Results: A wide variety of new therapies in NMIBC treatment are currently being developed, utilizing recent developments in the understanding of immune therapies and cancer biology. Conclusion: The ongoing efforts to develop new therapeutic approaches for NMIBC look very promising and are continuing to evolve.

Follow-up of negative MRI-targeted prostate biopsies: when are we missing cancer?

IntroductionMultiparametric magnetic resonance imaging (mpMRI) has improved clinicians’ ability to detect clinically significant prostate cancer (csPCa). Combining or fusing these images with the real-time imaging of transrectal ultrasound (TRUS) allows urologists to better sample lesions with a targeted biopsy (Tbx) leading to the detection of greater rates of csPCa and decreased rates of low-risk PCa. In this review, we evaluate the technical aspects of the mpMRI-guided Tbx procedure to identify possible sources of error and provide clinical context to a negative Tbx.MethodsA literature search was conducted of possible reasons for false-negative TBx. This includes discussion on false-positive mpMRI findings, termed “PCa mimics,” that may incorrectly suggest high likelihood of csPCa as well as errors during Tbx resulting in inexact image fusion or biopsy needle placement.ResultsDespite the strong negative predictive value associated with Tbx, concerns of missed disease often remain, especially with MR-visible lesions. This raises questions about what to do next after a negative Tbx result. Potential sources of error can arise from each step in the targeted biopsy process ranging from “PCa mimics” or technical errors during mpMRI acquisition to failure to properly register MRI and TRUS images on a fusion biopsy platform to technical or anatomic limits on needle placement accuracy.ConclusionsA better understanding of these potential pitfalls in the mpMRI-guided Tbx procedure will aid interpretation of a negative Tbx, identify areas for improving technical proficiency, and improve both physician understanding of negative Tbx and patient-management options.

Clinical implications of PET/CT in prostate cancer management

Several imaging modalities exist for the investigation of prostate cancer (PCa). From ultrasound to computed tomography (CT) and magnetic resonance imaging (MRI), the role of imaging in detecting lesion foci, staging, and localizing disease after biochemical recurrence (BCR) is expanding. However, many of the conventional imaging modalities are suboptimal, particularly in the detection of metastasis. Positron emission tomography (PET) has recently emerged as a promising tool in PCa management. The ability to develop radiolabeled tracers for functional imaging based on characteristics of PCa cells can potentially provide more insight into management by utilizing key features of those cells, such as metabolic activity, increased proliferation, and receptor expression. 18-flurodeoxyglucose (FDG) is one of the earliest tracers used in PET imaging that takes advantage of increased metabolism of glucose. Its role in PCa has been somewhat limited due to poor resolution and confounders including noise resulting from the proximity of the prostate to the bladder. Choline, a precursor molecule for a major component of the cell membrane, phosphatidylcholine, shows increased uptake in cells with rapid proliferation. When compared to metabolic based imaging techniques with FDG, choline PET/CT was superior. Nevertheless, choline PET/CT was not equivocal to MRI in detection of local disease, but was superior to conventional imaging in localizing metastasis and lymph node metastasis (LNM). Fluciclovine is another novel marker that utilizes the increased proliferation seen in tumor cells. Studies have shown it to be superior to choline PET/CT in PCa management, particularly in patients with BCR. As with choline PET/CT, studies that have assessed the impact of fluciclovine on clinical practice have highlighted the impact of these new tracers on clinical decision making. Most recently, the newest molecular probe targeting prostate specific membrane antigen (PSMA) was developed. It offers higher detection rates compared to choline PET/CT and conventional imaging modalities and has shown promise in LNM and BCR. With the wide range of available PET tracers, this review aims to highlight the role of each in lesion foci detection, primary staging, disease recurrence and explore the potential clinical impact.

Predicting Gleason Group Progression for Men on Prostate Cancer Active Surveillance: The Role of a Negative Confirmatory MRI-US Fusion Biopsy

Purpose: Active surveillance has gained acceptance as an alternative to definitive therapy in many men with prostate cancer. Confirmatory biopsies to assess the appropriateness of active surveillance are routinely performed and negative biopsies are regarded as a favorable prognostic indicator. We sought to determine the prognostic implications of negative multiparametric magnetic resonance imaging-transrectal ultrasound guided fusion biopsy consisting of extended sextant, systematic biopsy plus multiparametric magnetic resonance imaging guided targeted biopsy of suspicious lesions on magnetic resonance imaging. Materials and Methods: All patients referred with Gleason Grade Group 1 or 2 prostate cancer based on systematic biopsy performed elsewhere underwent confirmatory fusion biopsy. Patients who continued on active surveillance after a positive or a negative fusion biopsy were followed. The baseline characteristics of the biopsy negative and positive cases were compared. Cox regression analysis was used to determine the prognostic significance of a negative fusion biopsy. Kaplan-Meier survival curves were used to estimate Grade Group progression with time. Results: Of the 542 patients referred with Grade Group 1 (466) or Grade Group 2 (76) cancer 111 (20.5%) had a negative fusion biopsy. A total of 60 vs 122 patients with a negative vs a positive fusion biopsy were followed on active surveillance with a median time to Grade Group progression of 74.3 and 44.6 months, respectively (p <0.01). Negative fusion biopsy was associated with a reduced risk of Grade Group progression (HR 0.41, 95% CI 0.22-0.77, p <0.01). Conclusions: A negative confirmatory fusion biopsy confers a favorable prognosis for Grade Group progression. These results can be used when counseling patients about the risk of progression and for planning future followup and biopsies in patients on active surveillance.PURPOSEnActive surveillance has gained acceptance as an alternative to definitive therapy in many men with prostate cancer. Confirmatory biopsies to assess the appropriateness of active surveillance are routinely performed and negative biopsies are regarded as a favorable prognostic indicator. We sought to determine the prognostic implications of negative multiparametric magnetic resonance imaging-transrectal ultrasound guided fusion biopsy consisting of extended sextant, systematic biopsy plus multiparametric magnetic resonance imaging guided targeted biopsy of suspicious lesions on magnetic resonance imaging.nnnMATERIALS AND METHODSnAll patients referred with Gleason Grade Group 1 or 2 prostate cancer based on systematic biopsy performed elsewhere underwent confirmatory fusion biopsy. Patients who continued on active surveillance after a positive or a negative fusion biopsy were followed. The baseline characteristics of the biopsy negative and positive cases were compared. Cox regression analysis was used to determine the prognostic significance of a negative fusion biopsy. Kaplan-Meier survival curves were used to estimate Grade Group progression with time.nnnRESULTSnOf the 542 patients referred with Grade Group 1 (466) or Grade Group 2 (76) cancer 111 (20.5%) had a negative fusion biopsy. A total of 60 vs 122 patients with a negative vs a positive fusion biopsy were followed on active surveillance with a median time to Grade Group progression of 74.3 and 44.6 months, respectively (p <0.01). Negative fusion biopsy was associated with a reduced risk of Grade Group progression (HR 0.41, 95% CI 0.22-0.77, p <0.01).nnnCONCLUSIONSnA negative confirmatory fusion biopsy confers a favorable prognosis for Grade Group progression. These results can be used when counseling patients about the risk of progression and for planning future followup and biopsies in patients on active surveillance.

Added Value of Multiparametric Magnetic Resonance Imaging to Clinical Nomograms for Predicting Adverse Pathology in Prostate Cancer

Purpose We examined the additional value of preoperative prostate multiparametric magnetic resonance imaging and transrectal ultrasound/multiparametric magnetic resonance imaging fusion guided targeted biopsy when performed in combination with clinical nomograms to predict adverse pathology at radical prostatectomy. Materials and Methods We identified all patients who underwent 3 Tesla multiparametric magnetic resonance imaging prior to fusion biopsy and radical prostatectomy. The Partin and the MSKCC (Memorial Sloan Kettering Cancer Center) preradical prostatectomy nomograms were applied to estimate the probability of organ confined disease, extraprostatic extension, seminal vesicle invasion and lymph node involvement using transrectal ultrasound guided systematic biopsy and transrectal ultrasound/multiparametric magnetic resonance imaging fusion guided targeted biopsy Gleason scores. With radical prostatectomy pathology as the gold standard we developed multivariable logistic regression models based on these nomograms before and after adding multiparametric magnetic resonance imaging to assess any additional predictive ability. Results A total of 532 patients were included in study. When multiparametric magnetic resonance imaging findings were added to the systematic biopsy based MSKCC nomogram, the AUC increased by 0.10 for organ confined disease (p <0.001), 0.10 for extraprostatic extension (p = 0.003), 0.09 for seminal vesicle invasion (p = 0.011) and 0.06 for lymph node involvement (p = 0.120). Using Gleason scores derived from targeted biopsy compared to systematic biopsy provided an additional predictive value of organ confined disease (&Dgr; AUC 0.07, p = 0.003) and extraprostatic extension (&Dgr; AUC 0.07, p = 0.048) at radical prostatectomy with the MSKCC nomogram. Similar results were obtained using the Partin nomogram. Conclusions Magnetic resonance imaging alone or in addition to standard clinical nomograms provides significant additional predictive ability of adverse pathology at the time of radical prostatectomy. This information can be greatly beneficial to urologists for preoperative planning and for counseling patients regarding the risks of future therapy.

Comparison of Elastic and Rigid Registration during Magnetic Resonance Imaging/Ultrasound Fusion-Guided Prostate Biopsy: A Multi-Operator Phantom Study

Purpose The relative value of rigid or elastic registration during magnetic resonance imaging/ultrasound fusion guided prostate biopsy has been poorly studied. We compared registration errors (the distance between a region of interest and fiducial markers) between rigid and elastic registration during fusion guided prostate biopsy using a prostate phantom model. Materials and Methods Four gold fiducial markers visible on magnetic resonance imaging and ultrasound were placed throughout 1 phantom prostate model. The phantom underwent magnetic resonance imaging and the fiducial markers were labeled as regions of interest. An experienced user and a novice user of fusion guided prostate biopsy targeted regions of interest and then the corresponding fiducial markers on ultrasound after rigid and then elastic registration. Registration errors were compared. Results A total of 224 registration error measurements were recorded. Overall elastic registration did not provide significantly improved registration error over rigid registration (mean ± SD 4.87 ± 3.50 vs 4.11 ± 2.09 mm, p = 0.05). However, lesions near the edge of the phantom showed increased registration errors when using elastic registration (5.70 ± 3.43 vs 3.23 ± 1.68 mm, p = 0.03). Compared to the novice user the experienced user reported decreased registration error with rigid registration (3.25 ± 1.49 vs 4.98 ± 2.10 mm, p <0.01) and elastic registration (3.94 ± 2.61 vs 6.07 ± 4.16 mm, p <0.01). Conclusions We found no difference in registration errors between rigid and elastic registration overall but rigid registration decreased the registration error of targets near the prostate edge. Additionally, operator experience reduced registration errors regardless of the registration method. Therefore, elastic registration algorithms cannot serve as a replacement for attention to detail during the registration process and anatomical landmarks indicating accurate registration when beginning the procedure and before targeting each region of interest.

MP57-20 DELINEATION OF PROSTATE CANCER FROM BPH BY EXCESS PSA RELATIVE TO PREDICTED: A STUDY IN MEN UNDERGOING MRI-TARGETED BIOPSY

(82/172), and 40.7% (70/172) for csPCa. In primary biopsies without previous biopsy PCa detection rate was 68.8% (11/16). Detection rates for any PCa with one, two, three and with four or more negative biopsies were 47.8% (33/69), 43.8% (21/48), 48.1% (13/27) and 33.3% (4/12), respectively (p1⁄4 0.388). Detection rates for csPCa were 68.8% (11/16), 42% (29/69), 37.5% (18/48), 33.3% and 25.5% (3/12) in patients without, with one, two, three and with four previous biopsies, respectively (p1⁄40.265). CONCLUSIONS: In this cohort, there were high detection rates for both any PCa and for csPCa up to fourth round biopsies, even when simultaneous systematic biopsies were omitted. This technique therefore is an appropriate approach for persistent PCa suspicion after negative prostate biopsy as well as a primary biopsy technique in selected cases when systematic biopsies are rejected by patients. Even though statistically not significant, detection rate decreases with four or more negative prior biopsies.

Super-active surveillance: MRI ultrasound fusion biopsy and ablation for less invasive management of prostate cancer.

Multiparametric magnetic resonance imaging (mpMRI) of the prostate has allowed clinicians to better visualize and target suspicious lesions during biopsy. Targeted prostate biopsies give a more accurate representation of the true cancer volume and stage so that appropriate treatment or active surveillance can be selected. Advances in technology have led to the development of MRI and ultrasound fusion platforms used for targeted biopsies, monitoring cancer progression, and more recently for the application of focal therapy. Lesions visualized on mpMRI can be targeted for ablation with a variety of energy sources employed under both local and general anesthesia. Focal ablation may offer an alternative option for treating prostate cancer as compared to the well-established interventions of whole-gland radiation or prostatectomy. Focal ablation may also be an option for patients on active surveillance who wish to be even more active in their surveillance. In this review, we describe the advancements and development of fusion biopsies, the rationale behind focal therapy, and introduce focal ablative techniques for indolent prostate cancers (super-active surveillance), including cryoablation and focal laser ablation (FLA) and the subsequent MRI/biopsy surveillance.

Incidental bladder cancers found on multiparametric MRI of the prostate gland: a single center experience

PURPOSEnIn the era of multiparametric magnetic resonance imaging (mpMRI) of the prostate gland, incidental findings are occasionally discovered on imaging. We aimed to report our experience of detecting incidental bladder cancers on mpMRI of the prostate in asymptomatic patients without irritative voiding symptoms or microscopic or gross hematuria.nnnMETHODSnA retrospective review was performed on a prospectively maintained database of all men who underwent prostate mpMRI at our institution from 2012 to 2018. Patients who were found to have incidental bladder lesions were identified and baseline demographics, imaging and histopathologic data were recorded. All patients with incidental bladder lesion detection on mpMRI, not attributable to extension of prostate cancer, underwent cystoscopy in addition to a biopsy and/or transurethral resection of bladder tumor (TURBT) if warranted on cystoscopy.nnnRESULTSnThere were 3147 prostate mpMRIs performed during this period and 25 cases (0.8%) of incidental bladder lesions were detected. These patients did not have any presenting symptoms such as gross or microscopic hematuria to prompt bladder lesion workup. The largest diameter of incidentally discovered bladder lesions ranged from 0.4 cm to 1.7 cm. Of the 25 cases of incidental bladder lesions, five were suspected to be due to prostate cancer invasion into the bladder. Only two of these five patients underwent biopsy, which confirmed prostate adenocarcinoma in both cases. Of the 20 patients without suspected prostate cancer invasion of the bladder, four had no suspicious lesions on cystoscopy to warrant a biopsy. The remaining 16 patients had bladder lesions seen on cystoscopy and underwent a biopsy and/or TURBT. Three of these patients had benign features on pathology (urachal remnant, amyloidosis and inflammation) and the remaining 13 had stage Ta urothelial carcinoma. Seven of these patients had low-grade Ta tumors and six had high-grade Ta tumors. All patients were treated with standard management of TURBT with or without intravesical BCG. There have been no reported cases of recurrence or progression in any of the patients in our cohort at the median follow-up of 26 months (interquartile range,19-40 months).nnnCONCLUSIONnmpMRI of the prostate may yield incidental findings, such as small bladder tumors. Awareness of the possibility of incidental bladder lesions is important as 65% of lesions reported in the bladder, not attributable to extension of prostate cancer, proved to be bladder cancer. This may allow for early intervention for asymptomatic patients with undetected bladder cancer prior to disease progression.