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1. Relationship Between Baseline Prostate-specific Antigen on Cancer Detection and Prostate Cancer Death: Long-term Follow-up from the European Randomized Study of Screening for Prostate Cancer

Author

Remmers, Sebastiaan, Bangma, Chris H., Godtman, Rebecka A., Carlsson, Sigrid V., Auvinen, Anssi, Tammela, Teuvo L.J., Denis, Louis J., Nelen, Vera, Villers, Arnauld, Rebillard, Xavier, Kwiatkowski, Maciej, Recker, Franz, Wyler, Stephen, Zappa, Marco, Puliti, Donella, Gorini, Giuseppe, Paez, Alvaro, Lujan, Marcos, Nieboer, Daan, Schröder, Fritz H., and Roobol, Monique J.

Published
2023
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2. A 16-yr Follow-up of the European Randomized study of Screening for Prostate Cancer

Author

Hugosson, Jonas, Roobol, Monique J., Månsson, Marianne, Tammela, Teuvo L.J., Zappa, Marco, Nelen, Vera, Kwiatkowski, Maciej, Lujan, Marcos, Carlsson, Sigrid V., Talala, Kirsi M., Lilja, Hans, Denis, Louis J., Recker, Franz, Paez, Alvaro, Puliti, Donella, Villers, Arnauld, Rebillard, Xavier, Kilpeläinen, Tuomas P., Stenman, Ulf H., Godtman, Rebecka Arnsrud, Stinesen Kollberg, Karin, Moss, Sue M., Kujala, Paula, Taari, Kimmo, Huber, Andreas, van der Kwast, Theodorus, Heijnsdijk, Eveline A., Bangma, Chris, De Koning, Harry J., Schröder, Fritz H., and Auvinen, Anssi

Published
2019
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3. Abstract C003: RAMP 205: A phase 1b/2a study of gemcitabine, nab-paclitaxel, avutometinib, and defactinib in untreated metastatic pancreatic ductal adenocarcinoma

Author

Lim, Kian-Haut, primary, Hidalgo, Manuel, additional, O'Hara, Mark H., additional, Spencer, Kristen R., additional, Garrido-Laguna, Ignacio, additional, DeNardo, David G., additional, Bhambhani, Vijeta, additional, Patrick, Gloria, additional, Cheng, Yaofeng, additional, Coma, Silvia, additional, Pachter, Jonathan A., additional, and Denis, Louis J., additional

Published
2024
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5. The Prevention of Prostate Cancer

Author

Griffiths, Keith, Prezioso, Domenico, Turkes, A., Denis, Louis J., Schlag, P. M., editor, Senn, H. -J., editor, Kleihues, P., editor, Stiefel, F., editor, Groner, B., editor, Wallgren, A., editor, Rentchnik, P., editor, Ramon, Jacob, editor, and Denis, Louis J., editor

Published
2007
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7. Relationship Between Baseline Prostate-specific Antigen on Cancer Detection and Prostate Cancer Death:Long-term Follow-up from the European Randomized Study of Screening for Prostate Cancer

Author

Remmers, Sebastiaan, Bangma, Chris H., Godtman, Rebecka A., Carlsson, Sigrid V., Auvinen, Anssi, Tammela, Teuvo L.J., Denis, Louis J., Nelen, Vera, Villers, Arnauld, Rebillard, Xavier, Kwiatkowski, Maciej, Recker, Franz, Wyler, Stephen, Zappa, Marco, Puliti, Donella, Gorini, Giuseppe, Paez, Alvaro, Lujan, Marcos, Nieboer, Daan, Schröder, Fritz H., Roobol, Monique J., Remmers, Sebastiaan, Bangma, Chris H., Godtman, Rebecka A., Carlsson, Sigrid V., Auvinen, Anssi, Tammela, Teuvo L.J., Denis, Louis J., Nelen, Vera, Villers, Arnauld, Rebillard, Xavier, Kwiatkowski, Maciej, Recker, Franz, Wyler, Stephen, Zappa, Marco, Puliti, Donella, Gorini, Giuseppe, Paez, Alvaro, Lujan, Marcos, Nieboer, Daan, Schröder, Fritz H., and Roobol, Monique J.

Abstract

Background: The European Association of Urology guidelines recommend a risk-based strategy for prostate cancer screening based on the first prostate-specific antigen (PSA) level and age. Objective: To analyze the impact of the first PSA level on prostate cancer (PCa) detection and PCa-specific mortality (PCSM) in a population-based screening trial (repeat screening every 2–4 yr). Design, setting, and participants: We evaluated 25 589 men aged 55–59 yr, 16 898 men aged 60–64 yr, and 12 936 men aged 65–69 yr who attended at least one screening visit in the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial (screening arm: repeat PSA testing every 2–4 yr and biopsy in cases with elevated PSA; control arm: no active screening offered) during 16-yr follow-up (FU). Outcome measurements and statistical analysis: We assessed the actuarial probability for any PCa and for clinically significant (cs)PCa (Gleason ≥7). Cox proportional-hazards regression was performed to assess whether the association between baseline PSA and PCSM was comparable for all age groups. A Lorenz curve was computed to assess the association between baseline PSA and PCSM for men aged 60–61 yr. Results and limitations: The overall actuarial probability at 16 yr ranged from 12% to 16% for any PCa and from 3.7% to 5.7% for csPCa across the age groups. The actuarial probability of csPCa at 16 yr ranged from 1.2–1.5% for men with PSA <1.0 ng/ml to 13.3–13.8% for men with PSA ≥3.0 ng/ml. The association between baseline PSA and PCSM differed marginally among the three age groups. A Lorenz curve for men aged 60–61 yr showed that 92% of lethal PCa cases occurred among those with PSA above the median (1.21 ng/ml). In addition, for men initially screened at age 60–61 yr with baseline PSA <2 ng/ml, further continuation of screening is unlikely to be beneficial after the age of 68–70 yr if PSA is still <2 ng/ml. No case of PCSM emerged in the sub

Published
2023

8. Supplementary Data from ASN004, A 5T4-targeting scFv-Fc Antibody–Drug Conjugate with High Drug-to-Antibody Ratio, Induces Complete and Durable Tumor Regressions in Preclinical Models

Author

Smith, Roger A., primary, Zammit, David J., primary, Damle, Nitin K., primary, Usansky, Helen, primary, Reddy, Sanjeeva P., primary, Lin, Jun-Hsiang, primary, Mistry, Mahesh, primary, Rao, Niranjan S., primary, Denis, Louis J., primary, and Gupta, Sandeep, primary

Published
2023
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11. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up

Author

Schröder, Fritz H, Hugosson, Jonas, Roobol, Monique J, Tammela, Teuvo L J, Zappa, Marco, Nelen, Vera, Kwiatkowski, Maciej, Lujan, Marcos, Määttänen, Liisa, Lilja, Hans, Denis, Louis J, Recker, Franz, Paez, Alvaro, Bangma, Chris H, Carlsson, Sigrid, Puliti, Donella, Villers, Arnauld, Rebillard, Xavier, Hakama, Matti, Stenman, Ulf-Hakan, Kujala, Paula, Taari, Kimmo, Aus, Gunnar, Huber, Andreas, van der Kwast, Theo H, van Schaik, Ron H N, de Koning, Harry J, Moss, Sue M, and Auvinen, Anssi

Published
2014
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13. ENGOT-ov60/GOG-3052/RAMP 201: A phase 2 study of VS-6766 (RAF/MEK clamp) alone and in combination with defactinib (FAK inhibitor) in recurrent low-grade serous ovarian cancer (LGSOC).

Author

Banerjee, Susana N., primary, Monk, Bradley J., additional, Van Nieuwenhuysen, Els, additional, Moore, Kathleen N., additional, Oaknin, Ana, additional, Fabbro, Michel, additional, Colombo, Nicoletta, additional, O'Malley, David M., additional, Coleman, Robert L., additional, Oza, Amit M., additional, Pachter, Jonathan A., additional, Patrick, Gloria, additional, Denis, Louis J., additional, Leonard, Lorna, additional, and Grisham, Rachel N., additional

Published
2022
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14. A phase 2 study of VS-6766 (RAF/MEK clamp) RAMP 202, as a single agent and in combination with defactinib (FAK inhibitor) in recurrent KRAS mutant (mt) and BRAF mt non–small cell lung cancer (NSCLC).

Author

Camidge, D. Ross, primary, Reuss, Joshua E., additional, Spira, Alexander I., additional, Janne, Pasi A., additional, Rehman, Muneeb, additional, Pachter, Jonathan A., additional, Patrick, Gloria, additional, Denis, Louis J., additional, and Spigel, David R., additional

Published
2022
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15. Phase I trial of the RAF/MEK clamp VS-6766 in combination with everolimus using an intermittent schedule with expansion in NSCLC across multiple KRAS variants.

Author

Minchom, Anna Rachel, primary, Sanchez Perez, Vicky, additional, Morton, Cienne, additional, Manickavasagar, Thubeena, additional, Nintos, George, additional, Lai-Kwon, Julia Elizabeth, additional, Guo, Christina, additional, Tunariu, Nina, additional, Parker, Tom, additional, Prout, Toby, additional, Parmar, Mona, additional, Turner, Alison Joanne, additional, Finneran, Laura, additional, Hall, Emma, additional, Pachter, Jonathan A., additional, Denis, Louis J., additional, Spicer, James F., additional, and Banerji, Udai, additional

Published
2022
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19. PD13-04 PROSTATE CANCER SPECIFIC MORTALITY IN THE ERSPC TRIAL: WHAT IS THE ROLE OF SCREENING RESULT AND ADHERENCE

Author

Wetterauer, Christian, primary, Remmers, Sebastiaan, additional, Prause, Lukas W., additional, Hugosson, Jonas, additional, Tammela, Teuvo L.J., additional, Zappa, Marco, additional, Nelen, Vera, additional, Lujan, Marcos, additional, Denis, Louis J., additional, Paez, Alvaro, additional, Puliti, Donella, additional, Villers, Arnauld, additional, Rebillard, Xavier, additional, Godtman, Rebecka Arnsrud, additional, Bangma, Chris, additional, Schröder, Fritz H., additional, Auvinen, Anssi, additional, Manka, Lukas, additional, Seifert, Helge H, additional, Wyler, Stephen F., additional, Roobol, Monique J, additional, and Kwiatkowski, Maciej, additional

Published
2021
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22. Screening and prostrate-cancer mortality in a randomized European study

Author

Schroder, Fritz H., Roobol, Monique J., Tammela , Teuvo L.J., Ciatto, Stefano, Hugosson, Jonas, Nelen, Vera, Kwiatkowski, Maciej, Lujan, Marcos, Lilja, Hans, Zappa, Marco, Denis, Louis J., Recker, Franz, Bereguer, Antonio, Maattanen, Liisa, Bangma, Chris H., Aus, Gunnar, Villers, Arnauld, Rebillard, Xavier, van der Kwast, Theodorus, Blinjenberg, Bert G., Moss, Sue M., de Koning, Harry J., and Auvinen, Anssi

Subjects
Mortality -- Control, Mortality -- Prevention, Cancer -- Prevention, Cancer -- Risk factors, Cancer -- Diagnosis, Cancer -- Usage, Cancer -- Health aspects
Abstract

The European randomized study attempts to investigate the efficacy of screening with prostrate-specific-antigen (PSA) on reducing the rate of mortality from prostrate cancer. The results indicate that PSA-based screening was effective in reducing the incidence of mortality by 20%, however, had a high risk of over diagnosis.

Published
2009

23. ASN004, A 5T4-targeting scFv-Fc Antibody–Drug Conjugate with High Drug-to-Antibody Ratio, Induces Complete and Durable Tumor Regressions in Preclinical Models

Author

Smith, Roger A., primary, Zammit, David J., additional, Damle, Nitin K., additional, Usansky, Helen, additional, Reddy, Sanjeeva P., additional, Lin, Jun-Hsiang, additional, Mistry, Mahesh, additional, Rao, Niranjan S., additional, Denis, Louis J., additional, and Gupta, Sandeep, additional

Published
2021
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24. Prostate-Cancer Mortality at 11 Years of Follow-up

Author

Schröder, Fritz H., Hugosson, Jonas, Roobol, Monique J., Tammela, Teuvo L.J., Ciatto, Stefano, Nelen, Vera, Kwiatkowski, Maciej, Lujan, Marcos, Lilja, Hans, Zappa, Marco, Denis, Louis J., Recker, Franz, Páez, Alvaro, Määttänen, Liisa, Bangma, Chris H., Aus, Gunnar, Carlsson, Sigrid, Villers, Arnauld, Rebillard, Xavier, van der Kwast, Theodorus, Kujala, Paula M., Blijenberg, Bert G., Stenman, Ulf-Hakan, Huber, Andreas, Taari, Kimmo, Hakama, Matti, Moss, Sue M., de Koning, Harry J., and Auvinen, Anssi

Published
2012

26. Estrogens and aspects of prostate disease

Author

Prezioso, Domenico, Denis, Louis J, Klocker, Helmut, Sciarra, Alexandria, Reis, Mario, Naber, Kurt, Lobel, Bernard, Pacik, Dalibor, and Griffiths, Keith

Published
2007

28. European randomized study of screening for prostate cancer: progress report of Antwerp and Rotterdam pilot studies

Author

Schroder, Fritz H., Denis, Louis J., Kirkels, Wim, De Koning, Harry J., and Standaert, Bo

Subjects
Prostate cancer -- Diagnosis, Europeans -- Testing, Clinical trials -- Europe, Health
Abstract

Background. The feasibility of screening and early detection of prostate cancer are controversial issues at this time. To conduct a randomized screening study with prostate cancer mortality as the major endpoint is one possible solution to the present controversy. Methods. Eight pilot studies have been conducted in the Netherlands (Rotterdam) and Belgium (Antwerp) to evaluate the feasibility of a large scale European randomized study of screening for prostate cancer. Randomization and all other administrative steps necessary to conduct a large scale screening study were evaluated in the two centers. Participation rates were from 30%--42%. Essential adjustments in pilot protocols were made during the study and led to significant changes. Results. Administrative procedures necessary to run a large scale randomized study were successfully established at the two centers. The experience can be used to establish similar procedures in other European countries. Follow-up in the no screening arm and information with relation to the major endpoint, prostate cancer mortality, are not yet available. In the screening arm, detection rates varied from 3.2% to 3.6%. Major changes in the application of the screening tests made during the course of the pilot studies were the use of random biopsies for prostate specific antigen (PSA) values between 4 and 10 ng/ml as well as the biopsy indication for all suspicious lesions in those men with a PSA below 4.0 ng/ml. One-third of all cancer cases were detected in this latter group. The application of the screening tests to men with low PSA values is still under evaluation. Conclusions. The pilot studies led to a common, agreed set of minimal requirements for participation in the European study. These features include randomization, PC mortality as major endpoint, age 55--70 years, biopsy policy, rescreening interval, treatment policies, and follow-up. A randomized screening study seems to be feasible in Europe. Cancer 1995; 76:129--34. Key words: prostate cancer, screening, randomized study, pilot studies, screening tests, general population.

Published
1995

31. Clinical activity, safety and tolerability of ASN002, a dual JAK/SYK inhibitor, in patients with non-Hodgkin lymphoma (NHL), myeolfibrosis (MF), chronic lymphocytic leukemia (CLL) and solid tumors.

Author

Barta, Stefan K., primary, Rasco, Drew W., additional, Chen, Andy I., additional, Elkins, Stephanie, additional, Wang, Michael, additional, Denis, Louis J., additional, Toker, Sarper, additional, Usansky, Helen, additional, Reddy, Sanjeeva, additional, and Rao, Niranjan Sathyanarayana, additional

Published
2018
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32. Abstract B147: A phase 1 PK/PD study of ASN003, a novel, highly selective BRAF and PI3K dual inhibitor, in patients with advanced solid tumors

Author

Rasco, Drew, primary, Lakhani, Nehal, additional, Sullivan, Ryan, additional, Mita, Monica, additional, Shah, Jaimini, additional, Usansky, Helena, additional, Reddy, Sanjeeva, additional, Rao, Niranjan, additional, Denis, Louis J., additional, Tolcher, Anthony, additional, and Flaherty, Keith, additional

Published
2018
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34. Clinical activity and safety of ASN001, a selective CYP17 lyase inhibitor, administered without prednisone in men with metastatic castration-resistant prostate cancer (mCRPC): A phase 1/2 clinical trial.

Author

Garcia, Jorge A., primary, Dreicer, Robert, additional, Pantuck, Allan J., additional, Haas, Naomi B., additional, Vaishampayan, Ulka N., additional, Rao, Niranjan Sathyanarayana, additional, Denis, Louis J., additional, and Tolcher, Anthony W., additional

Published
2017
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38. First International Conference on Chemoprevention of Prostate Cancer

Author

THOMPSON, IAN M., ALBANES, DEMETRIUS, BASLER, JOSEPH W., CRAWFORD, E. DAVID, DENIS, LOUIS J., DJAVAN, BOB, FLESHNER, NEIL, JOHNSON-PAIS, TERESA L., KLEIN, ERIC A., KRISTAL, ALAN R., LUCIA, M. SCOTT, PARNES, HOWARD L., PIAZZA, GARY A., PLATZ, ELIZABETH A., POLLOCK, BRAD H., PRICE, DOUGLAS K., REICHARDT, JUERGEN K., TANGEN, CATHERINE M., TOLCHER, ANTHONY W., and McMANN, MARY CAROLE

Published
2004
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39. Absolute Effect of Prostate Cancer Screening: Balance of Benefits and Harms by Center within the European Randomized Study of Prostate Cancer Screening

Author

Auvinen, Anssi, primary, Moss, Sue M., additional, Tammela, Teuvo L.J., additional, Taari, Kimmo, additional, Roobol, Monique J., additional, Schröder, Fritz H., additional, Bangma, Chris H., additional, Carlsson, Sigrid, additional, Aus, Gunnar, additional, Zappa, Marco, additional, Puliti, Donella, additional, Denis, Louis J., additional, Nelen, Vera, additional, Kwiatkowski, Maciej, additional, Randazzo, Marco, additional, Paez, Alvaro, additional, Lujan, Marcos, additional, and Hugosson, Jonas, additional

Published
2016
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40. Development of a Standardized Set of Patient-centered Outcomes for Advanced Prostate Cancer: An International Effort for a Unified Approach.

Author

UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service d'urologie, Morgans, Alicia K, van Bommel, Annelotte C M, Stowell, Caleb, Abrahm, Janet L, Basch, Ethan, Bekelman, Justin E, Berry, Donna L, Bossi, Alberto, Davis, Ian D, de Reijke, Theo M, Denis, Louis J, Evans, Sue M, Fleshner, Neil E, George, Daniel J, Kiefert, Jim, Lin, Daniel W, Matthew, Andrew G, McDermott, Ray, Payne, Heather, Roos, Ian A G, Schrag, Deborah, Steuber, Thomas, Tombal, Bertrand, van Basten, Jean-Paul, van der Hoeven, Jacobus J M, Penson, David F, Advanced Prostate Cancer Working Group of the International Consortium for Health Outcomes Measurement, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service d'urologie, Morgans, Alicia K, van Bommel, Annelotte C M, Stowell, Caleb, Abrahm, Janet L, Basch, Ethan, Bekelman, Justin E, Berry, Donna L, Bossi, Alberto, Davis, Ian D, de Reijke, Theo M, Denis, Louis J, Evans, Sue M, Fleshner, Neil E, George, Daniel J, Kiefert, Jim, Lin, Daniel W, Matthew, Andrew G, McDermott, Ray, Payne, Heather, Roos, Ian A G, Schrag, Deborah, Steuber, Thomas, Tombal, Bertrand, van Basten, Jean-Paul, van der Hoeven, Jacobus J M, Penson, David F, and Advanced Prostate Cancer Working Group of the International Consortium for Health Outcomes Measurement

Abstract

BACKGROUND: There are no universally monitored outcomes relevant to men with advanced prostate cancer, making it challenging to compare health outcomes between populations. OBJECTIVE: We sought to develop a standard set of outcomes relevant to men with advanced prostate cancer to follow during routine clinical care. DESIGN, SETTING, AND PARTICIPANTS: The International Consortium for Health Outcomes Measurement assembled a multidisciplinary working group to develop the set. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used a modified Delphi method to achieve consensus regarding the outcomes, measures, and case mix factors included. RESULTS AND LIMITATIONS: The 25 members of the multidisciplinary international working group represented academic and nonacademic centers, registries, and patients. Recognizing the heterogeneity of men with advanced prostate cancer, the group defined the scope as men with all stages of incurable prostate cancer (metastatic and biochemical recurrence ineligible for further curative therapy). We defined outcomes important to all men, such as overall survival, and measures specific to subgroups, such as time to metastasis. Measures gathered from clinical data include measures of disease control. We also identified patient-reported outcome measures (PROMs), such as degree of urinary, bowel, and erectile dysfunction, mood symptoms, and pain control. CONCLUSIONS: The international multidisciplinary group identified clinical data and PROMs that serve as a basis for international health outcome comparisons and quality-of-care assessments. The set will be revised annually. PATIENT SUMMARY: Our international group has recommended a standardized set of patient-centered outcomes to be followed during routine care for all men with advanced prostate cancer.

Published
2015

41. Development of a Standardized Set of Patient-centered Outcomes for Advanced Prostate Cancer: An International Effort for a Unified Approach

Author

Morgans, Alicia K., primary, van Bommel, Annelotte C.M., additional, Stowell, Caleb, additional, Abrahm, Janet L., additional, Basch, Ethan, additional, Bekelman, Justin E., additional, Berry, Donna L., additional, Bossi, Alberto, additional, Davis, Ian D., additional, de Reijke, Theo M., additional, Denis, Louis J., additional, Evans, Sue M., additional, Fleshner, Neil E., additional, George, Daniel J., additional, Kiefert, Jim, additional, Lin, Daniel W., additional, Matthew, Andrew G., additional, McDermott, Ray, additional, Payne, Heather, additional, Roos, Ian A.G., additional, Schrag, Deborah, additional, Steuber, Thomas, additional, Tombal, Bertrand, additional, van Basten, Jean-Paul, additional, van der Hoeven, Jacobus J.M., additional, and Penson, David F., additional

Published
2015
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42. Metastatic Prostate Cancer Incidence and Prostate-specific Antigen Testing: New Insights from the European Randomized Study of Screening for Prostate Cancer

Author

Buzzoni, Carlotta, primary, Auvinen, Anssi, additional, Roobol, Monique J., additional, Carlsson, Sigrid, additional, Moss, Sue M., additional, Puliti, Donella, additional, de Koning, Harry J., additional, Bangma, Chris H., additional, Denis, Louis J., additional, Kwiatkowski, Maciej, additional, Lujan, Marcos, additional, Nelen, Vera, additional, Paez, Alvaro, additional, Randazzo, Marco, additional, Rebillard, Xavier, additional, Tammela, Teuvo L.J., additional, Villers, Arnauld, additional, Hugosson, Jonas, additional, Schröder, Fritz H., additional, and Zappa, Marco, additional

Published
2015
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43. RAMP 202: A phase 2 study of avutometinib (VS-6766) ± defactinib, in patients with advanced KRAS G12V mutant non–small cell lung cancer (NSCLC).

Author

Reuss, Joshua E., Gandhi, Sunil G., Spigel, David R., Janne, Pasi A., Paz-Ares, Luis G., Gadgeel, Shirish M., Patel, Jyoti D., Passiglia, Francesco, Spira, Alexander I., Edelman, Martin Joseph, Blumenschein, George R., Shergill, Ardaman, Burns, Timothy F., Bhambhani, Vijeta, Patrick, Gloria, Pachter, Jonathan A., Denis, Louis J., and Camidge, D. Ross

Published
2023
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46. Development of a patient-reported outcome (PRO) measure for assessing non-small cell lung cancer (NSCLC) symptoms in clinical trials: Interim report from the PRO Consortium’s NSCLC Working Group (WG).

Author

Campbell, Alicyn K., primary, Martin, Mona L., additional, Arduino, Jean Marie, additional, Atkinson, Thomas Michael, additional, Lundy, J. Jason, additional, Lungershausen, Juliane, additional, Denis, Louis J., additional, and Liepa, Astra M., additional

Published
2014
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47. Endocrine treatment in prostate cancer

Author

Denis, Louis J. and Griffiths, Keith

Subjects
Human medicine
Abstract

Over its natural course, prostate cancer is a heterogeneous tumour with a generally slow but constant rate of growth. The androgen dependence of the prostate gland was demonstrated more than half a century ago by the landmark studies of Professor C. Huggins and colleagues. They established that androgens are implicated not only in growth regulation of the normal gland but also in the pathogenesis of prostate cancer, and that this malignant tissue retains some degree of androgen dependence. This concept was supported by studies of symptomatic clinical cancer, with androgen ablative therapy bringing relief to the patient in more than 80% of the cases. The classical treatment consisted of either bilateral orchiectomy, or administration of diethylstilbestrol (DES). Other forms of therapy followed, involving successive waves of new compounds that either withdrew androgen support from the cancer or blocked the androgens from their receptors in the prostate cancer cells. Chronologically, the progestagens can be well recognised, with one in particular: The successful derivative, cyproterone acetate (CPA). There also have been a number of oral vs. parenteral estrogens, the development of the luteinizing hormone-releasing hormone agonists (LH-RHA), the introduction of the non-steroidal anti-androgens characterised by flutamide and casodex, and more recently, the introduction of the LH-RHA. Moreover, there have been multiple possible forms of combination treatment to obtain maximal androgen blockade (MAB). However, no major differences in treatment outcome have been reported during the last 5 decades and most treatment choices have been based on tradition, associated side effects, the preferences of a particular doctor and patient, together with economic considerations. Furthermore, endocrine treatment has never been shown to curl clinical prostate cancer, which consequently has led to initiatives to defer endocrine treatment or to use it intermittently or use it as a form of neo-adjuvant or adjuvant treatment with surgery or radiotherapy. The history of endocrine therapy is replete with clinical trials that do not represent the patient population in general, and these trials share the clinical fact that they ignore the 20% to 30% of all patients who lack an initial response to a given endocrine treatment. Thus, it is no wonder that prognostic factors determine the outcome more than the treatment itself. Important to current endocrine treatment, however, is the shift to earlier stages of prostate cancer at initial diagnosis. Integration of endocrine treatment at this earlier phase in the pathogenesis of prostate cancer will substantially alter the treatment strategy in relation to long-term benefit with regard to survival, associated side effects, and costs. This complex adjustment is enhanced by recent discoveries in the molecular biology of the prostate which show, on the one hand, that the dihydrotestosterone-androgen receptor (DHT-AR) complex is important in the regulation of gene expression, but also that a number of intrinsic factors (e.g., peptide growth regulatory factors) can, through various paracrine, autocrine or intracrine interactions, exercise a major influence on cellular homeostasis and the regulation of prostatic growth. (C) 2000 Wiley-Liss, Inc.

Published
2000

48. Active surveillance for low-risk prostate cancer

Author

Bangma, Chris H., primary, Bul, Meelan, additional, van der Kwast, Theo H., additional, Pickles, Tom, additional, Korfage, Ida J., additional, Hoeks, Caroline M., additional, Steyerberg, Ewout W., additional, Jenster, Guido, additional, Kattan, Michael W., additional, Bellardita, Lara, additional, Carroll, Peter R., additional, Denis, Louis J., additional, Parker, Chris, additional, Roobol, Monique J., additional, Emberton, Mark, additional, Klotz, Laurence H., additional, Rannikko, Antti, additional, Kakehi, Yoshiyuki, additional, Lane, Janet A., additional, Schröder, Fritz H., additional, Semjonow, Axel, additional, Trock, Bruce J., additional, and Valdagni, Riccardo, additional

Published
2013
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