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Targeting the cancer lesion, not the whole prostate.

ABSTRACT: Modern cancer treatment aims to conserve as much healthy tissue as possible. This has been challenging in the treatment of prostate cancer due to the difficulty in imaging the gland and concerns over leaving multifocal cancer untreated. With improvements in imaging and understanding of multifocal prostate cancer evidence now shows accurate treatment of just the primary focus of cancer or the index lesion can control progression or recurrence of the disease. Many different energy sources are now available to target the cancer lesion within the prostate with less significant side-effects on urinary and sexual function compared to radical treatment. Evidence shows that men value these functions highly and would even trade years of life in exchange for preserved retention of continence or erectile function. Focal treatment of prostate cancer aims to provide both cancer control and preservation of sexual and urinary functions so that men do not have to make a choice between the two. This is a treatment option that men clearly want and deserve.

SUBMITTER: Bedi N

PROVIDER: S-EPMC7354301 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Targeting the cancer lesion, not the whole prostate.

Bedi Nishant N Reddy Deepika D Ahmed Hashim U HU

Translational andrology and urology 20200601 3

Modern cancer treatment aims to conserve as much healthy tissue as possible. This has been challenging in the treatment of prostate cancer due to the difficulty in imaging the gland and concerns over leaving multifocal cancer untreated. With improvements in imaging and understanding of multifocal prostate cancer evidence now shows accurate treatment of just the primary focus of cancer or the index lesion can control progression or recurrence of the disease. Many different energy sources are now ...[more]

PMID: 32676439

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Project description:ObjectivesTo determine the accuracy of nodal staging in patients with prostate cancer (PCa) when 99 m Tc-nanocolloid radiotracer is injected into an index lesion (IL).MethodsThis prospective study was conducted at our institution between June 2016 and October 2020. It included 64 patients with localized PCa with at least a 5% possibility for lymph node involvement in the Memorial Sloan Kettering Cancer Center nomogram, suitable for surgical treatment. All patients underwent magnetic resonance imaging (MRI) with IL and were pathologically confirmed. The day before surgery, transrectal ultrasound-guided injection (TRUS) of 99 m Tc-nanocolloid into the IL was performed. Surgical procedures included radical prostatectomy (RP), sentinel lymph node biopsy (SLNB), and extended pelvic lymphadenectomy (ePLND). Analysis was performed, including histopathological findings of RP, ePLND, and SLNB. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), false negative (FN), false positive (FP), diagnostic yield, and non-diagnostic rate were calculated.ResultsA total of 1,316 lymph nodes were excised, including 1,102 from the ePLND (83.7%) and 214 (16.3%) sentinel lymph nodes (SLN). 26 SLN were dissected outside the ePLND template. The final pathology demonstrated 46 (3.5%) lymph node metastasis, 31 (67.4%) in the SLNB and 15 (32.6%) in the non-SLN ePLND. At the patient level, 18 (28.1%) patients had pN1. With a mean follow-up of 33.1 months, 4/19 (21.1%) pN1 patients had undetectable PSA, and 3/19 (15.8%) had a PSA < 0.1 ng/mL. Lymph node dissection included 20.6 lymph nodes per patient (IQR 15-24.2), with 3.3 SLNB nodes per patient (IQR 2-4.2). PPV and NPV were 100 and 97.8%, respectively. Sensitivity and specificity were 94.4 and 100%, respectively. FN was 5.5% and FP was 4.3%. Diagnostic yields were 95.3% and the non-diagnostic rate was 4.7%.ConclusionRadiotracer injection into the prostate IL offers promising results for staging purposes in cases in which ePLND is considered. Negative SLNB is a predictor of negative ePLND. Patients with a limited burden of nodal metastasis have a significant chance of remaining free of biochemical recurrence at mid-term follow-up.

Project description:BackgroundBone biopsies in metastatic castrate-resistant prostate cancer (mCRPC) patients can be challenging. This study's objective was to prospectively validate a multiparametric bone MRI (mpBMRI) algorithm to facilitate target lesion selection in mCRPC patients with sclerotic bone disease for subsequent CT-guided bone biopsies.Methods20 CT-guided bone biopsies were prospectively performed between 02/2021 and 11/2021 in 17 mCRPC patients with only sclerotic bone disease. Biopsy targets were selected based on MRI, including diffusion-weighted (DWI) and T1-weighted VIBE Dixon MR images, allowing for calculation of the apparent diffusion coefficient (ADC) and the relative fat-fraction (rFF), respectively. Bone marrow with high DWI signal, ADC < 1100 µm2/s and rFF < 20% was the preferred biopsy target. Tumor content and NGS-feasibility was assessed by a pathologist. Prognostic routine laboratory blood parameters, target lesion size, biopsy tract length, visual CT density, means of HU, ADC and rFF were compared between successful and unsuccessful biopsies (p < 0.05 = significant).ResultsOverall, 17/20 (85%) biopsies were tumor-positive and next-generation genomic sequencing (NGS) was feasible in 13/18 (72%) evaluated samples. Neither laboratory parameters, diameter, tract length nor visual CT density grading showed significant differences between a positive versus negative or NGS feasible versus non-feasible biopsy results (each p > 0.137). Lesion mean HU was 387 ± 187 HU in NGS feasible and 493 ± 218 HU in non-feasible biopsies (p = 0.521). For targets fulfilling all MRI selection algorithm criteria, 13/14 (93%) biopsies were tumor-positive and 10/12 (83%) provided NGS adequate tissue.ConclusionsMultiparametric bone MRI can facilitate target lesion selection for subsequent CT-guided bone biopsy in mCPRC patients with sclerotic metastases.Trial registrationCommittee for Clinical Research of the Royal Marsden Hospital registration number SE1220.

Project description:Anoikis is a mode of apoptotic cell death, consequential to insufficient cell-matrix interactions and a critical player in tumor angiogenesis and metastasis. The events involved in tumor cell progression toward metastasis potential are mediated by integrins, which upon engagement with components of the extracellular matrix (ECM), reorganize to form adhesion complexes. Targeting apoptotic players is of immense therapeutic significance since resistance to apoptosis is not only critical in conferring therapeutic failure to standard treatment strategies, but anoikis (apoptosis upon loss of anchorage and detachment from ECM) also plays an important role in angiogenesis and metastasis. The ability to survive in the absence of adhesion to the ECM, enables tumor cells to disseminate from the primary tumor site, invade a distant site and establish a metastatic lesion. Tumor cells can escape from detachment-induced apoptosis by controlling anoikis pathways, including the extrinsic death receptor pathway and the ECM-integrin mediated cell survival pathway. Considering the functional promiscuity of individual signaling effectors, it is critical to dissect the molecular networks mechanistically driving tumor cells to evade anoikis and embark on a metastatic spread. Resistance to die via anoikis dictates tumor cell survival and provides a molecular basis for therapeutic targeting of metastatic prostate cancer. Further dissection of critical anoikis signaling events will enable the therapeutic optimization of anoikis targeting to impair prostate cancer metastasis prior to its initiation. This review will discuss the molecular understanding of anoikis regulation in the tumor microenvironment and the in vivo pharmacological implementation of a novel class of antitumor-drugs to optimize apoptotic-based therapeutic targeting, bypassing anoikis-resistance to impair prostate cancer progression to metastasis. Potential combination strategies targeting tumor vascularity (via anoikis) and impairing tumor initiation (via "classic" apoptosis), provide strong therapeutic promise for metastatic prostate cancer by preventing the onset of metastasis.

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Targeting the cancer lesion, not the whole prostate.

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Targeting the cancer lesion, not the whole prostate.

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