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Monday, February 19, 2007

Historical Developments in Prostate Cancer

[Updated June 4, 2008]


1593 - Andreas Vesalius illustrates prostate gland
1853 - prostate cancer identified as a disease
1895 - first orchiectomy performed but with limited success
[White JW. The results of double castration in hypertrophy of the
prostate. Ann Surg 1895. 22:1-80. [link]]
1904 - Hugh Young performs first radical perineal prostatectomy at John Hopkins [PMID: 11905922]
1909 - prostate cancer treated by radium implant for first time
1941 - Charles B. Huggins publishes studies showing relationship between
testosterone and prostate cancer [PMID: 12050481].
Also see this May 26, 2007 article that appeared in the Montreal Gazette.
1945 - First retropublic prostatectomy. [PMID: 11905927]
195? - TURP replaced radical prostatectomy for relief of obstruction
1966 - Huggins receives Nobel Prize
1966 - Gleason grading system is introduced
1970 - PSA discovered [PMID: 4986767] [PMID: 15023439]
1971 - Folkman proposes anti-angiogenesis to combat cancer. [PMID: 4938153].
Its unknown, even today, whether this will result in a breakthrough
in prostate cancer treatment but its listed here just in case.
1971 - Andrew Schally discovers and synthesizes LHRH, a factor in prostate
cancer growth
1977 - Andrzej W. Schally and Roger Guillemin win Nobel Prize for work in
GnRH reproduction (which led to the development of receptor
antagonists leuprolide and goserelin used to treat prostate cancer.
See the section on Testosterone Production in the Body in [link]
for a discussion.)
1980 - PSA found to be elevanted in men with prostate cancer
1981 - McNeal details zonal anatomy of the prostate. [PMID: 7279811].
1982 - Patrick Walsh performs first nerve sparing prostatectomy. Patient
is Robert E. Hastings. (Date of surgery was April 26, 1982.) See Nerve Sparing Turns 25.
1983 - Brachytherapy established as treatment for localized prostate cancer
1986 - PSA test approved by FDA for monitoring cancer recurrence
1987 - DVC bunching surgical technique introduced reducing blood loss significantly.
[PMID: 2625855] [PMID: 2681837]

1990 - studies prove heredity is a risk factor in prostate cancer
1990 - 3D conformal radiation treatment introduced
1992 - laparascopic radical prostatectomy introduced; however, it was not until 1998 that it was in regular use according to Touijer & Guillonneau, 2006
1994 - PSA test approved by FDA for screening [FDA Announcement]
1995 - lycopene shown to reduce risk of prostate cancer
1997 - IMRT introduced
1998 - FDA approves sildenafil (Viagra)
1998 - First laparascopic prostatectomy using modern techniques [PMID: 10799152] according to Rodrigues and Pow-Sang
1999 - US Medicare accepts cryosurgery

2000 - hormone therapy shown to be effective for advanced prostate cancer
2001 - three studies show fish consumption protects against prostate cancer
2005 - discovery of antibodies that act as a new biomarker for prostate cancer
2006 - European study discovers unique genetic variance in some men
2008 - Dr. Donald Gleason, developer of the Gleason score dies, Dec 28th. See LA Times article.


Mitchell Sokoloff

Forecast Mitchell H. Sokoloff

2008 - "(1) definitive prospective comparison studies of cancer control and quality-of-life outcomes in open and robotic prostatectomy; (2) expanded stratification of risk among patients with localized disease; (3) improved standardization of adjuvant and salvage therapies for preventing and treating recurrent disease; and (4) results from phase 3 trials investigating new systemic therapies for prostate cancer."

Fleshner and Zlotta

Prevention Trials Estimated to Complete Fleshner and Zlotta (2007)

2008 - 325 person NCIC soy, vitamin E and selenium PCa prevention trial
2010 - GTX toremifene (selective estrogen receptor modulator) PCa prevention trial. 8200 HGPIN men.
2010 - GSK dutasteride PCa prevention trial. 8200 high risk men.
2011 - SWOG selenium PCa prevention trial. 700 men.
2012 - SWOG selenium and vitamin E (SELECT) trial. 32,400 healthy men.


Robotic surgery will get sensory feedback technology. Intuitive Surgical already has access to the technology. See [this post].


At the AUA 2007 Buenos Aires meeting, Dr. Michael J. Zelefsky of Sloan Kettering mentioned Image Guided Radiation Therapy (IGRT) which uses markers placed within the prostate for image guidance is expected to become the next generation of radiotherapy after IMRT. Being precise to 1 mm it will allow higher dosages of radiation to be delivered to diseased tissue while reducing radiation to healthy tissue.


Greco (2007) forecasts that Proton therapy will be combined with IMRT-like computer control with the combination referred to as IMPT; however, at the AUA 2007 Buenos Aires meeting Michael Zelefsky cautioned that such development is not expected too soon due to the $100 million cost and space requirements of these platforms.

New York Times

The New York Times have a Dec 26, 2007 article that says:
On the horizon is therapy using beams of carbon ions, which are said to be even more powerful in killing tumors. Touro University says it will build a combined proton and carbon therapy center outside San Francisco, to open as early as 2011. The Mayo Clinic is also seriously considering one. Such centers will cost even more - as much as $300 million.


There are Phase II/III trials of HIFU (ultrasound therapy which kills prostate cells through the heat action of ultrasound without dangerous radiation) which should ultimately lead to availability of this therapy in the US. Currently it is available in many other countries but not the US. Furthermore, "technical improvements in HIFU are pending, including an MRI-guided HIFU treatment. MRI is now able to monitor the temperature achieved in the target volume during a HIFU pulse. An automated adjustment of the treatment parameters according to the temperature measured in the target volume could be done in real time to control the heat extension during the HIFU session, thus optimizing the treatment efficacy." See Murat et al (July, 2007).


Better biomarkers will be developed which may make active surveillance safer due to more accurate entry and exit criteria.


Alan Meyer, a patient, posted this summary of promising developments on March 7, 2008.

Prostate Cancer Research Foundation of Canada

Forecast (by Prostate Cancer Research Foundation of Canada)

2015 - molecular profiling replaces biopsy in diagnosis
2015 - prostate cancer gene is identified and diagnostics and preventive
drugs made available

Prostate Cancer Foundation

The Prostate Cancer Foundation founded by financier Michael Milken has used a portfolio approach for issuing $19 million in research grants and a review of the areas illustrates the topics thought to have the greatest upcoming promise. See Prostate Cancer Foundation Grants More Than $19 Million to Cancer Research Programs . The topics are:
  • Progression Biomarkers whose development would increase the pace of all future research since one would know sooner when experimental drugs are working
  • blocking ETS Gene Fusions to arrest prostate cancer, since it was found that tumors create their own androgens
  • since it was discovered that tumors produce their own androgens simply reducing them in the blood is insufficient so this project would look into reducing them in the tumor itself
  • better characterize models that predict when new drugs are working in order to speed up research
  • study nutrition, obesity, diabetes, bone fracture and heart disease for patients receiving treatment for advanced prostate cancer
  • epigenetic cellular alterations are genetic mutations that are independent of DNA sequence. Study and work toward the new medications which block these.
  • discover blood markers indicating an immune response to prostate cancer and use this to develop immunotherapy treatments
  • study prostate cancer stem cells


Johan Stranne, Inguinal Hernia after Urologic Surgery in Males with Special Reference to Radical Retropubic Prostatectomy, A Clinical, Epidemiological and Methodological Study. Department of Urology, Institute of Clinical Sciences, The Sahlgrenska Academy at Göteborg University, Sahlgrenska University Hospital, Göteborg 2006, pages 7-11. [link]

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