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Prostate cancer is a disease that presentsa wide spectrum from low aggressiveness localized todisseminated cancer. Locally advanced prostate cancer(LAPC) is a particularly difficult to manage phase of thisspectrum.OBJECTIVES: We review the definition, diagnosis andtreatment of this phase of the disease.METHODS: We performed a non systematic literaturereview of the most relevant features of this pathology.RESULTS: LAPC is more aggressive than organ confineddisease. Its clinical diagnosis is not always easy. Localtreatment, in spite of being aggressive with potential sequelae, seems to be advantageous in terms of patientsurvival.CONCLUSIONS: Prostate cancer local staging iscurrently based on multiparametric magnetic resonanceimaging (mpMRI). Local radical treatment with surgeryor radiotherapy, with probable addition of systemictreatment, offers promising results for disease control andquality of life improvement
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Oligometastatic prostate cancer has been proposed as an intermediate stage between localized and extensively disseminated disease. Oligometastatic disease is being diagnosed more frequently due to the advances in imaging tests. Nevertheless, there is no consensus definition yet of oligometastatic prostate cancer. The importance of this entity is that several studies have pointed out that local and metastasis directed treatment may improve survival in selected patients. However, we need the results of well controlled prospective randomized clinical trials to help a better understanding and management of oligometastatic prostate cancer.
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OBJECTIVE: To analyze the current available evidence of androgen deprivation therapy in hormone-sensitive metastatic prostate cancer, focused on the relevance of suppressing circulating testosterone levels and its prognostic significance. To assess the optimal value of castration levels and PSA reduction under hormone treatment.METHODS: We performed a bibliographic review through automatized search in the Pubmed bibliographic database and Clinical Key. The search strategy included the following terms: “prostate cancer” AND “hormones”, “metastatic prostate cancer”, “testosterone” AND “prostate cancer”, “hormone naive/sensitive” AND “prostate cancer”.RESULTS: Lower testosterone levels are associated with better survival and have prognostic significance. Values below 32-20 ng/dl, in accordance to different reported studies, have been established as optimal castration levels with clinical significance, with impact on cancer specific survival and time to castration resistance. Similarly, low PSA levels after starting hormone therapy have been suggested as a strong predictor of survival and treatment response. CONCLUSIONS: Close monitoring of PSA and testosterone levels is necessary in patients with metastatic prostate cancer during hormone deprivation treatment. Combination of both values allows to predict treatment response and early identification of tumor progression, and to put forward subsequent therapeutic strategies improving survival in this group of patients.
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OBJECTIVES: Prostate cancer is linked to bone disease by two different entities. On one hand, androgen deprivation therapy (ADT) usually causes osteoporosis, on the other a great number of patients with advanced prostate cancer will present bone metastases, that condition not only their vital prognosis but also an important quality of life deterioration. METHODS: We performed a bibliographic review on both the physiology and therapy of osteoporosis secondary to ADT and bone metastasis in prostatic neoplasias. RESULTS: Osteoporosis: Long term ADT is associated with osteopenia/osteoporosis in 80% of the patients, with a 5-20% incidence of osteoporotic fractures. We should monitor bone mineral density before starting ADT therapy and during treatment. Treatment is based on risk factors reduction, regular physical exercise, calcium and vitamin D supplements, and drugs such as biphosphonates or denosumab. Bone metastasis: Currently, both zolendronic acid and denosumab have approval for the prevention of skeletal events in patients with castration resistant prostate cancer (CPRC). Although the last one seems to be more effective, it is associated with a higher risk of hypocalcemia and jaw osteonecrosis so that the choice of drug must be individualized in every patient. The duration of treatment is not clear. Currently, the indication for the use of this drugs in earlier phases of advanced disease is not approved. CONCLUSIONS: Comprehensive management of the patient with advanced prostate cancer should include the study and treatment of osteoporosis and bone metastases. Currently, very effective therapies are available for both entities.
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OBJECTIVES: The treatment of metastaticprostate cancer has remained unchanged for more than70 years, based on androgen deprivation therapy (ADT).In 2015, following the CHAARTED and STAMPEDEtrials, it was established that the addition of 6 cyclesof docetaxel to ADT was associated with significantlyincreased survival. In June 2017, the LATITUDE trialand the G arm of the STAMPEDE trial showed that theaddition of Abiraterone with Prednisone (5 mg/day) toADT was also associated with a significant increase insurvival in metastatic patients. The present study analyzesthese two trials.RESULTS: LATITUDE demonstrated a 38% reduction inthe risk of death (HR=0.62, 95% CI, 0.61-0.76) inalmost all sub-groups. Risk reduction for radiologicalprogression was 53% (HR=0.47, 95% CI 0.39-0.55).Secondary objectives such as prostate specific antigenprogression, time to chemotherapy or a new skeletalevent are also significantly delayed.STAMPEDE also showed that the combination ofAbiraterone and Prednisone is associated with a37% increase in survival (HR=0.63, 95% CI, 0.52-0.76, p<0.001) in metastatic patients, but not in nonmetastaticpatients. Progression-free survival was greatlyimproved in this arm (HR=0.29, 95% CI 0.25-0.34,p<0.001). The side effects reported show the knownpattern of mineral corticosteroid excess with increasedblood pressure, hypokalemia, and of liver enzymeselevation.CONCLUSIONS: The indirect comparison of docetaxeland abiraterone studies confirms that both populationsand results are comparable. Two comparative indirectmetanalysis (>6000 patients) gave marginal superiorityto abiraterone. In favor of abiraterone we have that it isan oral, comfortable medication with a good toleranceprofile and side effects that are easy to manage,useful in patients who are old and fragile, in whomchemotherapy may not be indicated; the downsides areprolonged exposure to the drug and its current price.Future trials, currently in progress, will determine theideal patient profile, or a potential association of boththerapies.
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OBJECTIVE: Several studies haveassessed the role of adding chemotherapy to hormonaltreatment for metastatic hormone-sensitive prostatecancer (MHSPC). The objective of this manuscript is toreview these studies and to provide recommendationsfor the management of these patients.METHODS: We identified published clinical trialscomparing hormone blockade (HB) with HB plusdocetaxel as first-line treatment of HSMPC and weanalyzed their results in terms of efficacy and toxicity.RESULTS: Of the 3 trials published, two demonstratedincreased overall survival by adding docetaxel tothe first-line treatment of MHSPC (CHAARTED and Stampede-Docetaxel studies) and the third one didnot show such an advantage (GETUG-AFU15). In theCHAARTED study, the survival advantage was limitedto patients presenting high tumor volume. Toxicity wasincreased in patients who received docetaxel.CONCLUSIONS: The addition of docetaxel to treatmentwith HB should be considered in patients with MHSPC,especially in those with high tumor volume. However,the toxicity and recent results of trials performed withabiraterone in MHSPC should also be taken inconsideration.
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Prostate cancer is the most frequent malignanttumor in males in developed countries and representsthe second cause of cancer death.Over the last years, the number of treatments availablefor patients with advanced prostate cancer has improvedsignificantly, achieving better disease control andnotably better overall survival (1).Corticosteroids have been extensively used in the treatmentof castration resistant prostate cancer due to theirpalliative benefits on symptoms secondary to their potentanti-inflammatory activity and their demonstrated antitumoractivity. At present time, we have a wide therapeuadreticarsenal for patients with metastatic prostate cancerand concomitant medication with corticosteroids maycounteract adverse events of the main validated therapies.Nevertheless, long term exposition to corticosteroidtreatment required by prostate cancer patients mayhave negative implications in terms of development ofpotential adverse events and, in certain cases, even facilitatingdisease progression.
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OBJECTIVES: Metastatic prostate cancer is a very heterogeneous disease with several treatment options. In some cases of oligometastatic disease, local treatment of the primary tumor complemented by metastasis directed therapy seems to improve oncological results. The objectives of this study are to define and understand oligometastatic prostate cancer, to show the usefulness and rationale of cytoreductive surgery in this scenario and to review all published studies about radical prostatectomy in patients with initially metastatic prostate cancer. METHODS: We performed a Pubmed bibliographic search using the keywords: prostate cancer, metastatic, oligometastatic, local treatment, radical prostatectomy, and cytoreductive surgery. We included all published works on radical prostatectomy in initially metastatic patient. Furthermore, we reviewed published articles about cytoreductive surgery and biology of the oligometastatic disease in journals of different medical specialties. RESULTS: Oligometastatic prostate cancer is recognized as an intermediate clinical stage between local and disseminated disease that seems to benefit from local treatment of the primary tumor plus metastasis directed treatment. In this scenario, different retrospective studies have demonstrated that radical prostatectomy diminishes local complication rate and improves oncological results without increasing morbidity. Currently, there is no consensus definition about the number, location, and imaging techniques to employ to consider a patient oligometastatic. Thus, it is difficult to compare the results of the different studies and identification of a subgroup of patients that could benefit from this local treatment. CONCLUSIONS: In absence of prospective randomized data, radical prostatectomy seems to be useful for local treatment of the primary tumor in a selected group of patients with oligometastatic prostate cancer.
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OBJECTIVES: We elaborate the bases and rationale for the application of multimodal extended treatment including local radiotherapy in patients with oligometastatic prostate cancer (omPCa). We performed a bibliographic review on the state of the art in this field and propose a therapeutic strategy that incorporates ablative radiotherapy of the primary tumor +/- oligometastatic lesions.METHODS: We performed a comprehensive literature review consulting different sources that include data bases (Pubmed/Medline), and international treatment guidelines ((NCCN, NCI, EUA). Search criteria: Locally advanced prostate cancer, oligometastatic, disseminated and radiotherapy, ablative or stereotactic radiotherapy (SBRT). RESULTS: The most accepted definition for oligometastatic prostate cancer or oligotopic prostatic neoplasia is when we recognize at least 3 non-visceral metastatic lesions in an extrapelvic location. Whole body MRI and PET scan (Choline/PSMA) are non conventional useful tests for staging in the workup for oligometastatic disease. From a clinical point of view, omPCa behaves as an intermediate entity between locally advanced and disseminated or multimetastatic prostate cancer. Androgen deprivation therapy (ADT) represents the base of treatment for castration sensitive PCa. To date there is no biological marker/genetic sign identified that differentiate aggressiveness profiles in omPca. Most evidence on the use of radiotherapy for this entity comes from retrospective studies, showing a benefit in control and prevention of local symptoms. To date, the survival benefit derived from the application of local treatment to the primary tumor with demonstrable metastatic disease is uncertain, and it has not been shown in the available randomized prospective clinical trials.CONCLUSIONS: Primary tumor radiotherapy in omPca positively influences local control and prevention of local symptoms progression. The level of evidence to recommend prostatic radiotherapy as a therapeutic variable with impact on survival on omPca is limited (Level 2B-3 Category). Research lines in omPca deserve the inclusion of a multimodal systemic treatment including ADT, ablative radiotherapy for the tumor and consolidation radiotherapy in metastatic distant lesions
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OBJECTIVES: The therapeutic range inadvanced and castration resistant prostate cancer is widening.Therapies must offer real clinical efficacy, andthey also should be acceptable and desirable for patients,specially in advanced disease. We analyze thevalue of quality of life analysis in patients with advancedprostate cancer.METHODS: We performed a bibliographic review (Pubmed)with the various health related quality of life scalesavailable and different clinical trials on advanced prostatecancer.RESULTS: There are numerous therapeutic options but,due to variations in study design, a different evaluationof adverse events and different therapeutic regimens,comparisons are difficult. A common method to interpretresults is not available, so most of the times that interpretationis left to statistical significance, which is notalways well correlated with clinical significance.CONCLUSIONS: To propose the most adequate treatmentin patient`s interest, we need results focused onpatients that combine not only quantity or overall survivalbut also quality of life. Parameters such as QALY shouldbe included in clinical trials as evaluation objectives inorder to favor decision taking.
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In the last decade, prostate cancermanagement has dramatically evolved to such acomplexity that different medical specialties have toparticipate for its optimization, even making necessaryin many cases super specialization in every disciplinefor such aim.All Guidelines and every Scientific Association dorecommend multidisciplinary teams for its managementas a rule, but translation from multidisciplinary committeesto daily assistance is heterogeneous and faces, manytimes, particular interests and conflicts between differentspecialties implying that objective information of all thetherapeutic options does not reach the patient to enrollhim in his own therapeutic pathway.This is an opinion paper reviewing the advantages ofthe multidisciplinary team daily work as a prolongationof the multidisciplinary committee decisions, relyingin the literature to set the legal framework andrecommendations to generate an operative and realmodel of multidisciplinary teamwork for the benefit ofboth patient and all professionals involved in prostatecancer management.
