Metastatic patterns of prostate cancer: An autopsy study of 1,589 patients
Institute of Pathology and Urologic Clinics, University of Basel, Switzerland. Human Pathlogy
(Impact Factor: 2.77).
The prognosis of prostate cancer is mainly determined by the presence or absence of metastases. Nevertheless, the metastatic pathways in prostate cancer are not entirely understood. Among 19,316 routine autopsies performed from 1967 to 1995 on men older than 40 years of age, the reports from those 1,589 (8.2%) with prostate cancer were analyzed. Hematogeneous metastases were present in 35% of 1,589 patients with prostate cancer, with most frequent involvement being bone (90%), lung (46%), liver (25%), pleura (21%), and adrenals (13%). Several lines of evidence suggested the existence of a backward metastatic pathway through veins from the prostate to the spine in addition to classical hematogeneous tumor spread via the vena cava. First, there was an inverse relationship between spine and lung metastases, suggesting that metastasis to the spine is independent of lung metastasis. Second, the maximum frequency of spine involvement occurred in smaller tumors (4 to 6 cm) as compared with the maximum spread to lung (6 to 8 cm) and liver (>8 cm), suggesting that spine metastases precede lung and liver metastases in many prostate cancers. Third, there was a gradual decrease in spine involvement from the lumbar to the cervical level (97% v 38%), which is consistent with a subsequent upward metastatic spread along spinal veins after initial lumbar metastasis. The results of this study show that bone, lung, and liver are the most frequent sites of distant prostate cancer metastases. Besides the cava-type of metastasis through lung passage, there are strong arguments for the existence and clinical significance of a backward venous spread to the spine, which is likely to occur early in the metastatic process.
Available from: Hendrik Paul Van Poppel
- "Most patients who present with metastatic disease at diagnosis or with disease recurrence after potentially curative therapy with prostatectomy or radiation therapy respond to castration with androgen deprivation therapy ; however, progression to castration-resistant disease usually occurs within 2–3 yr  . Ultimately, almost all patients who progress after androgen deprivation therapy develop metastatic castration-resistant prostate cancer (mCRPC)  , and more than 90% of patients with mCRPC develop bone metastases, which produces significant morbidity in many men and is associated with increased mortality  . "
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ABSTRACT: Metastatic castration-resistant prostate cancer (mCRPC) often involves bone, and bone-targeted therapy (BTT) has become part of the overall treatment strategy.
Investigation of outcomes for concomitant BTT in a post hoc analysis of the COU-AA-302 trial, which demonstrated an overall clinical benefit of abiraterone acetate (AA) plus prednisone over placebo plus prednisone in asymptomatic or mildly symptomatic chemotherapy-naïve mCRPC patients.
This report describes the third interim analysis (prespecified at 55% overall survival [OS] events) for the COU-AA-302 trial.
Patients were grouped by concomitant BTT use or no BTT use.
Radiographic progression-free survival and OS were coprimary end points. This report describes the third interim analysis (prespecified at 55% OS events) and involves patients treated with or without concomitant BTT during the COU-AA-302 study. Median follow-up for OS was 27.1 mo. Median time-to-event variables with 95% confidence intervals (CIs) were estimated using the Kaplan-Meier method. Adjusted hazard ratios (HRs), 95% CIs, and p values for concomitant BTT versus no BTT were obtained via Cox models.
While the post hoc nature of the analysis is a limitation, superiority of AA and prednisone versus prednisone alone was demonstrated for clinical outcomes with or without BTT use. Compared with no BTT use, concomitant BTT significantly improved OS (HR 0.75; p=0.01) and increased the time to ECOG deterioration (HR 0.75; p<0.001) and time to opiate use for cancer-related pain (HR 0.80; p=0.036). The safety profile of concomitant BTT with AA was similar to that reported for AA in the overall intent-to-treat population. Osteonecrosis of the jaw (all grade 1/2) with concomitant BTT use was reported in <3% of patients.
AA with concomitant BTT was safe and well tolerated in men with chemotherapy-naïve mCRPC. The benefits of AA on clinical outcomes were increased with concomitant BTT.
Treatment of advanced prostate cancer often includes bone-targeted therapy. This post hoc analysis showed that in patients with advanced prostate cancer who were treated with abiraterone acetate and prednisone in combination with bone-targeted therapy, there was a continued trend in prolongation of life when compared with patients treated with prednisone alone.
Copyright © 2015. Published by Elsevier B.V.
Available from: Timur R Samatov
- "Bone is often a target for breast cancer metastases (Chambers et al., 2002) and up to 90% of metastatic prostate cancer patients have lesions in the bones upon autopsy (Bubendorf et al., 2000). "
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ABSTRACT: The metastatic cascade comprises the following steps in sequential manner: the future metastatic cell has to leave the primary tumor mass, degrade the surrounding extracellular matrix, extravasate and circulate within in the bloodstream. Thereafter it has to attach to the endothelium of a target organ, intravasate into the connective tissue and has to proliferate to form a clinically detectable metastasis. We overview the in vitro microfluidic platforms modelling the metastatic cascade and the evolution towards systems capable of recapitulating all the steps by a single comprehensive model.
Copyright © 2015. Published by Elsevier GmbH.
Available from: PubMed Central
- "Prostate cancer (PCa) is the most common malignancy and the second leading cause of cancer-related mortality in males in western countries. Advanced and metastatic stages of the disease were present in 35% of 1,589 patients with PCa diagnosed by autopsy (1). Among those patients with localized cancer who are able to receive radical prostatectomy (RP), ~35% will develop a recurrence (metastatic disease) within the 10 years following surgery (2,3). "
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ABSTRACT: Prostate cancer (PCa) remains a major cause of mortality among males in western countries, with little change in mortality rates observed over the past 25 years. Despite recent advances in therapy, treatment options for metastatic castration-resistant disease remain limited. In terms of chemotherapy, only the combination of docetaxel and prednisone has been shown to improve survival in these patients, but duration of response to therapy is short. There is a continuing unmet need for new systemic interventions that act either alone or synergistically with chemotherapy in patients with progressive PCa. Angiogenesis plays a critical role in tumor growth and metastasis in PCa. Several strategies have been used to target angiogenesis; however, it is becoming increasingly apparent that current anti-angiogenic therapies frequently achieve only modest effects in clinical settings. The RhoA/Rho kinase (ROCK) pathway plays a crucial role in the process of angiogenesis in PCa, and studies have demonstrated that ROCK inhibitors decrease VEGF-induced angiogenesis and tumor cell growth. However, further research is required to fully elucidate the molecular mechanisms involved in this pathway, and the potential value of modulating these mechanisms in the treatment of PCa. This study reviews the current understanding of the role of the RhoA/ROCK pathway in the process of angiogenesis in PCa, and the potential of this pathway as a therapeutic target in the future.
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