Patients with low and intermediate risk prostate cancer are the most frequently diagnosed group currently. In those with a life expectancy inferior to 10 years it is highly likely that treatment is not necessary so that observation must be the most appropriate approach.In patients in whom active therapy, in any of its forms, is indicated, it is necessary to balance between risk of dying or developing metastases from the disease and adverse effects of commonly accepted radical treatments, such as radical prostatectomy and external beam or interstitial radiotherapy. The significant incidence of associated morbidity, mainly erectile dysfunction and urinary incontinence, with high impact on quality of life, demands this approach in the field of decisions shared with patients.The risk of overtreatment in this group of patients has generated the introduction of more conservative approaches such as active surveillance and focal therapy. The first one tries to differ radical treatments as far as there are not enough aggressiveness criteria on the tumor or the patient requests them. The second, called to have a place between active surveillance and radical treatments, involves the performance of a partial ablation of the prostate to avoid the adverse effects of radical treatments, trying to achieve the closest oncological control to the radical options.We perform a review of the therapeutic options and their results in this type of patients.
Prostate Cancer (PCa) remains anexception among solid cancers since organ-sparingprocedures are not considered as a standard option.Despite most men harbour low to intermediate riskdisease at diagnosis, the vast majority are advisedtowards radical treatment. We performed a literaturereview to highlight and discuss why focal therapy (FT)would represent a feasible and attractive option inappropriately selected men. The rationale supporting this strategy relies in epidemiological, pathological,molecular and clinical findings. These include the shifttowards the diagnosis of less aggressive and unifocalPCas, the presence of an identifiable index lesion whichdrives the natural history of the disease together with theabsence of significant disease elsewhere in the glandin many patients. New diagnostic tools, especiallymultiparametric MRI, allow the detection of the indexlesion with good accuracy and high reliability. FT mightprovide acceptable disease control and at the sametime substantially reduce treatment related side-effects inthose men who are eligible for such strategy. To allowits adoption as a standard of care, future studies needto address current limitations such as the lack of directcomparative research against standard treatment, aswell as long-term disease-control outcomes.
OBJECTIVES: Prostate cancer (PCa) is the most common form of cancer among men in the US and the second most common cause of death. It has been observed that an increasing number of newly diagnosed patients exhibit low-risk features and that over-treatment with radical prostatectomy is a growing problem. The feasibility of focal therapy as an organsparing alternative, however, depends on the reliability of imaging techniques to identify, localize and monitor clinically relevant PCa lesions. The aim of this review is to investigate the potential of multiparametric ultrasound (mpUS) for focal therapy.METHODS: We briefly introduce the most common focal therapies and thoroughly discuss the ability of available ultrasound modalities to localize PCa and reflect tissue properties. The imaging requirements of the focal therapies are studied to put the performance of the US techniques into perspective.RESULTS: We found that transrectal greyscale echography, Doppler sonography, elastography, contrast-enhanced ultrasonography and computerized ultrasound have been studied for the purpose of prostate imaging. Several of these modalities are already frequently used in current clinical practice; to add to the diagnostic process of PCa, to guide and monitor the application of focal therapy or to perform follow-up after treatment. Despite their capability to detect a large fraction of the PCa lesions, none of these modalities is currently considered sufficiently accurate for stand-alone tumour detection and localization. However, although there are only few studies reporting on a combined use of different ultrasound modalities, the results of an mpUS approach seem promising.CONCLUSION: Several US modalities have been successfully applied as a viable alternative to monitor tissue destruction during and after treatment. In view of the advantages of US and the promising results of a multiparametric approach in PCa detection and localization, researchers are urged to further investigate mpUS for therapeutic purposes.
The use of prostatic multiparametric MRI (mpMRI) has increased significantly over the last years, and has emerged as a crucial test for diagnosis, staging and treatment of prostate cancer (PCa).The use of the various available sequences (T2W, T1W, diffusion, perfusion and spectroscopy), as well as the different parameters they associate, not only enables to determine the group of patients subsidiary of focal ablative therapy, but also to perform a proper determination of the áreas to treat, as well as to monitor the development of therapy and to evaluate both oncological results and possible therapeutic failures.Despite the excellent results showed in the different studies, it is necessary to reach a consensus about its use on the different features associated with focal therapy, since it is a technique that requires not only large experience in its operation but also standardization. All this make it a complex technique and not free of difficulties in its interpretation.
Despite advances in the diagnosis of prostate cancer over the past century, it remains a leading cause of cancer related death. A recent recommendation against screening has further complicated the diagnosis and management of this condition. It remains to be demonstrated if newer diagnostic modalities will have an impact on mortality rates. Most certainly, not all prostate cancers need to be diagnosed, and methods of accurately diagnosing those cancers that lead to death needs more work. In this review article, we describe the different techniques, approaches and diagnostic accuracies of the currently used biopsy methods.
High Intensity Focused Ultrasound(HIFU) is a heat based energy source used for tissueablation. HIFU has several clinical applications andprostate cancer ablation is one of the uses that havebeen explored for more than a decade. Focal therapyis an alternative treatment option for selected patientswith low/intermediate PCa, that is based on completeablation of tumor within the prostate with preservation ofnormal parenchyma and better preservation of Genitourinaryfunctions. In spite of PCa being predominantlya multi-centric disease, it is postulated that a specificdominant (large volume) ‘index lesion’ dictates thebiological behavior of the cancer and subsequent lethalityof the disease. The use of HIFU for focal ablation ofPCa, have demonstrated satisfactory cancer control withfewer morbidity and better preservation of continenceand erection. The aim of this article is to present thereaders with a brief review of the principles, devicesavailable for clinical uses, published clinical experienceand future directions and research opportunities in focalHIFU ablation of prostate cancer.
OBJECTIVE: To systematically review the oncological and functional outcomes of contemporary primary prostate focal cryotherapy for localized prostate cancer in the context of current developments in prostate focal therapy.METHODS: We performed a systematic search of the Pubmed, Cochrane and Embase databases to identify studies where primary prostate focal cryotherapy was performed to treat prostate cancer. These included reports on focal/ lesion/ sector ablation, hemi-ablation and partial prostate ablation. We excluded salvage focal therapy studies. Where multiple reports were published over time from a single cohort, the latest one was used.RESULTS: Our search yielded 290 publications, including 17 primary reports on eight single-center cohort studies and one multi-center registry report. Of 1,595 men identified, mean age was 60.5-69.5 years and mean PSA 5.1-7.8 ng/ml. When stratified by D’Amico risk criteria, 52% of the aggregate total number of men were low-risk, 38% intermediate-risk and 10% high-risk. Besides 12-core TRUS biopsy, 3 cohorts reported using TTMB and one included mpMRI to select men for focal treatment. Median follow-up ranged from 13-63 months. BPFS ranged from 71-98%. The overall post-treatment positive biopsy rate was 8-25%. Among 5 cohorts with a mandatory 6-12 month posttreatment biopsy, 216 of 272 men (79%) did undergo biopsy, with 47 positive (21.8%). Of these, 15 were infield, 26 outfield, 2 bilateral and 4 undeclared. Ten upgraded to Gleason≥7. Overall, two men had metastatic disease and none died of prostate cancer. Post-treatment continence rates were 96-100% and rates of erectile dysfunction ranged from 0-42%. The rate of post-treatment urinary retention ranged from 0-15%. The rate of recto-urethral fistula was 0-0.1%.CONCLUSION: Focal cryotherapy for localized prostate cancer is a safe and provides good preservation of sexual and urinary function. Accurate cancer localization and risk stratification is key to patient selection. In highly selected patients, focal therapy has good short to medium term oncological efficacy.
The increase of the diagnosis of low riskprostate cancer translates into a new clinical entity, forwhich active surveillance may not be always enoughand conventional therapies are clearly overtreatment.Faced with the necessity of giving a therapeutic answerto these patients, and facilitated by the technologicaladvances in the imaging field and new energy sources,the interest is centered in the clinical development offocal therapies as an alternative with minimal morbidityand oncologically safe.As a part of the review carried out in this monographicissue, this article focus on the features relative to thepreclinical and clinical development of laser ablativetherapy and the innovative photodynamic vasculartherapy with soluble TOOKAD®. With this aim weperformed an exhaustive bibliographic search, updated to February 2016, in the greater databases, includingoriginal articles and reviews in reference to the object ofthis review, without restrictions for year of publication. Thisarticle reviews the preclinical and clinical developmentof these innovative ablative techniques in the field offocal therapy for low risk prostate cancer
The extensive use of prostate-specific antigen (PSA) testing and improved imaging technologies have resulted in an increased diagnosis of prostate cancer. Early diagnosis is often accompanied by an increased number of localized (i.e. unifocal or unilateral), small-volume and low-grade prostate cancers. Focal therapy is an emerging treatment option in prostate cancer, targeting individual cancer areas while sparing important functional and anatomical urological structures. Irreversible electroporation is an innovative treatment modality in focal therapy based on Arch. Esp. Urol. 2016; 69 (6): 337-344337the process of cell membrane electroporation limiting damage to adjacent tissue and vital structures. The first phase I-II trials in humans have shown the safety of IRE for focal ablative therapy of prostate cancer and showed encouraging results considering functional preservation. Histological analysis after IRE showed fibrosis without glandular ducts and necrotic tissue with sharp demarcation between unaffected prostatic glandular tissue and the ablation zone. Short-term oncological results are promising; however more data on long-term oncological outcomes are necessary. New studies with IRE and other focal treatment modalities are initiated to explore opportunities for focal therapy in prostate cancer and to optimize current treatment protocols.
Focal therapy has settled as an alternative to radical treatment in selected cases of localized prostate cancer. The selection of patients who are candidates for focal therapy is based on imaging diagnosis relying on multiparametric MRI and image fusion techniques. Thanks to the oncological results and safety profiles of initial series, various energy sources have been developed over the last years. The availability of multiple types of energy sources for focal therapy, commits us to evaluate what type of energy would be the optimal depending on patient´s profile and type of lesion.A unique energy for focal therapy would be ideal, but facing the research of the various types of energy we must identify which one is recommended for each lesion. With the experience of our center in different approaches of focal therapy we propose the “A LA CARTE” MODEL based on localization of the lesion. We present the criteria the “a la carte” model is based on, supported by the published evidence on the use of different ablative therapies for the treatment of localized prostate cancer. Lesion localization, technical characteristics of each type of energy, patient`s profile and secondary effects must be considered in every choice of focal therapy.
FocalyxTM conceived as a response toemerging evidence data across numerous cancer lesionsthat questions current standard treatment approachesthat too often lead to detrimental quality of life yetdelivering limited survival benefit, especially in-lieu ofadvances in imaging technology applicable to cancerpatients. The Focalyx paradigm aims to control cancerwith improvement in quality of life. We initially devised5 milestones: 1- Consistently optimize Prostate MRIimaging using the novel published protocols adoptedas guidelines by societies such as the European Societyof Urology and Radiology; 2- Evaluate fusion platformsoftware solutions that existed; 3- Determine best fusion platform for Focalyx on practicality, precision, andworkflow premises; 4- Evaluate commercially availableFDA approved ablative technologies to implement ourtreatment vision; 5- Design a treatment option that canbe performed in the office setting under local anesthesia,which would not impact negatively QOL outcomes ofProstate Cancer patients and seamless constant nonintrusivepractical patient-physician interaction by theFocalyx app that facilitates follow up and providesearly warning signals shall any change in the diseasedynamics emerge. Prostate cancer was identified asthe pilot disease for Focalyx to deliver a “GPS” likesolution for the prostate gland that destroys identifiabledisease without adverse effects such as: cancer anxiety,urinary incontinence, loss of erections and ejaculation.Since September of 2013, over 300 men have beenaccrued in NCT02381990- clintrials.gov evaluatingthe feasibility of our solutions for imaging (FocalyxDx),Biopsy (FocalyxBx) and Treatment (FocalyxTx). In thisreview we detail the tools available to achieve theFocalyx paradigm for men with Prostate Cancer.
OBJECTIVE: Focal therapy (FT) is a tissuesparing treatment paradigm for localized prostate cancer (PCa) with the potential to improve functional outcomes while maintaining oncologic safety. This paper aims to provide an overview of important considerations and practical recommendations relating to the follow-up after FT.METHODS: Literature review of papers related to FT in PCa derived from Medline/Pubmed database. RESULTS: The recommended minimum follow-up period after FT is 5 years. Standard history taking should include: signs of disease progression, treatment-related complications and psychological aspects. Oncological outcome is based on serial prostate specific antigen monitoring, follow-up imaging (most commonly with multiparametric magnetic resonance imaging) and repeat biopsies (systematic from entire gland or targeted from treated zone). Significant PCa has been found at biopsy in up to 17% of patients after FT. Functional outcomes are evaluated using standardized questionnaires that relate to urinary function, erectile function and quality of life. A systematic review reports urinary continence in 83-100% of patients, erections sufficient for penetration in 54-100%. Outcomes differ between ablative energies and treatment templates. The most common side effects after FT are urinary retention (0-17%), urinary tract infection (UTI) (0-17%) and urinary stricture (0-5%). Rectal fistula is a rare complication occurring in up to 0.1-2% of patients. Clavien-Dindo Grade 3-4 complications are reported in 0-4% of patients. Type and rate vary with treatment modality. Complications should be reported using standardized reporting systems. Most data on FT outcomes come from small heterogeneous trials. Pooling of standardized data is necessary to advance the field of FT.CONCLUSION: Stringent follow-up after FT is required to confirm oncologic safety of the individual patient. Standardized data gathering and data pooling is necessary to evaluate whether FT can live up to its promise of improving functional outcomes while maintaining oncological safety.
Focal therapy is a novel treatment option in localised prostate cancer with or without a visible lesion on MRI. Treatment for low to intermediate risk prostate cancer with focal therapy has demonstrated good short to medium term outcomes with fewer undesirable genitourinary side effects. This has made focal therapy more appealing to men who find the implications of radical treatment unacceptable or are unable to tolerate active surveillance. In this paper we review the literature for treatment options in prostate cancer recurrence post focal therapy. We also cover the different definitions of failure agreed upon in previous consensus meetings, as well as their implications on future management focal therapy patients.