PSA Velocity, Helpful by Itself?

Current guidelines for the early detection of prostate cancer recommend a biopsy for men whose P.S.A. rises rapidly, no matter what the initial level. But a new study says that the practice does not help patients find aggressive cancers and that it results in many unnecessary biopsies.

P.S.A., or prostate-specific antigen, rises with age, and what is considered normal varies. In general, a level under 4 nanograms per milliliter is considered safe. But even with a normal reading, an increase of 0.35 nanograms per year is widely believed to be high enough to require a biopsy.

Researchers examined the records of 5,519 men with a base-line P.S.A. under 3. They followed them for seven years with yearly tests and a biopsy if the level rose above 4.

They also analyzed P.S.A. velocity — the rate of change in readings from year to year. But after adjusting for age, base-line P.S.A. and other factors, they found little evidence that giving a biopsy to men whose velocity was greater than 0.35 helped find prostate cancer. And it was particularly useless in uncovering the most aggressive types of cancer, the ones most important to treat.

The researchers, writing in the March 16 issue of The Journal of the National Cancer Institute, concluded that using P.S.A. velocity for prostate cancer detection is ineffective, that it leads to unnecessary biopsies and that references to it should be removed from professional guidelines and policy statements.

Andrew J. Vickers, the lead author, drew an analogy: A basketball player’s height, he said, is important to his ability to play, and it correlates very closely with his shoe size. But once you know his height, his shoe size is irrelevant to judging his value as a player.

Similarly, it is easy to demonstrate a statistical relationship between sharp rises in P.S.A. and cancer, but the correlation reveals no more information than is already available with a P.S.A. reading, a digital examination and a family history. It is irrelevant in deciding whether a biopsy is needed.

Not all experts agree. Dr. Anthony V. D’Amico, a professor of radiation oncology at Harvard, said that the methodology of Dr. Vickers’s study was sound, but that the data gathered were almost certainly flawed.

The problem, Dr. D’Amico said, is that many factors that have nothing to do with prostate cancer can cause a rapid increase in prostate-specific antigen. Sexual activity, riding on a bicycle or on horseback, a recent colonoscopy, a bladder or prostate infection, even variations in the ways laboratories perform the test can radically affect the readings.

“It may well be that the high velocity in your case is not important,” he said. “But before you reach that conclusion, I would get a repeat P.S.A.” If there is still a spike after eliminating those other possible causes, he continued, a biopsy should be the next step.

Dr. Vickers, a researcher at Memorial Sloan-Kettering Cancer Center in New York City, agreed that prostate cancer was only one of many reasons for a high P.S.A. “A doctor sees a high P.S.A. and says, ‘Could this be cancer or some other reason?’ ” he said. “Well, the thought was that P.S.A. velocity could help you think this through” — that measuring the rate of change would be decisive.

But in practice, Dr. Vickers said, it does not work. If he had strictly applied the guidelines to the men in his study, he said, one in every seven would have had to have a biopsy. This would mean millions of American men would need biopsies, he said, with almost none of them revealing a cancer.

Dr. Vickers and his colleagues acknowledged that there might be better methods of calculating P.S.A. velocity that could lead to more accurate predictions, and that some effect might have been found if the patients had been followed for more than seven years.

But at this point, he is firmly against biopsies on the basis of velocity alone. “If your P.S.A. is in the normal range, you shouldn’t get a biopsy,” he said. “Changes or spikes in P.S.A. are not something to worry about if your P.S.A. is still normal.”

sequencing the complete DNA of an individual organism's genome.

Today’s announcement regarding the sequencing of whole prostate cancer genomes is an historic development in the fight against prostate cancer. The ability to sequence whole genomes will spare some patients from unnecessary treatments and side effects while eliminating an estimated $1.5 billion that is spent each year on overtreatment. The complete research findings will be published in the February 10 issue of Nature.

What is whole genome sequencing?
It is the process of sequencing the complete DNA of an individual organism's genome.

How much information is this?
If the DNA sequence of the human genome were compiled into books, it would fill 200 volumes of a Manahattan-sized phone book (or one 35-foot high phone book.) People won't be carrying this data around on flash drives either - it would still take a significant hard drive to store all of this information.

What did this research do?
Researchers mapped the complete genome of prostate cancer. They took the genetic material from the tumors of seven patients with advanced prostate cancer and then compared these cancer genomes to the normal genomes of these same patients. This information is visually presented using a Circos plot.

What is a Circos plot?
A Circos plot is a diagram created with Circos software for visualizing data in a circular layout. It was originally designed to aid in the visualization of genomic data.

Here are the Circos plots of the seven prostate cancer patients' genomes:




What does this mean for men diagnosed with prostate cancer?
The data expands our fundamental understanding of the disease’s biology and provides the technical and clinical roadmap for improving patient treatment and outcomes. Ultimately, every patient with prostate cancer will get a Circos plot with the whole genome sequencing of their biopsy as a unique portrait of the code that makes their prostate cancer manifest as it does.

How much does it cost to sequence a whole genome?
The current estimated cost of sequencing a whole genome is $25,000 or less. Experts predict that the cost of routine sequencing will ultimately be around $5,000 per genome. (This figure compares favorably to the cost of $90,000-$150,000 per patient for a radical prostatectomy followed by several years of androgen deprivation therapy using Lupron.)

Research Background
Work conducted by lead institutions, The Broad Institute, Dana-Farber Cancer Institute and Weill Cornell Medical College, along with 15 other collaborating institutions, completed this initial project ahead of a planned NIH effort.

Teleconference
The Prostate Cancer Foundation (PCF) hosted a teleconference to provide insight and commentary from leading professionals in the field. Click on the image above right to listen to the teleconference.

Listen to the Teleconference



Teleconference Participants:

Dr. Jonathan W. Simons (moderator)
President & CEO, PCF
Dr. Levi Garraway (Co-lead investigator)
Dana-Farber Cancer Institute, The Broad Institute

Dr. Michael Berger
Memorial Sloan-Kettering Cancer Center
Dr. Mark Rubin (Co-lead investigator)
Weil Cornell Medical College

Dr. Ash Tewari
Weill-Cornell Medical College
Dan Zenka
VP of Communications & Patient Advocate, PCF


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Provenge Treatment Results to Date(Jan 2011)

Sipuleucel-T is an autologous active cellular immunotherapy used in the treatment of men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (CRPC). It is the first therapeutic cancer vaccine to receive US FDA approval. Approximately 3 days prior to each infusion of sipuleucel-T, patients undergo a leukapheresis procedure for collection of autologous peripheral blood mononuclear cells. Preparation of sipuleucel-T involves enrichment for antigen-presenting cells from the leukapheresis product and activation ex vivo with a recombinant fusion protein (PA2024). In the randomized, double-blind, placebo-controlled IMPACT study in patients with metastatic CRPC, sipuleucel-T was associated with a 22% relative reduction in the risk of death (hazard ratio 0.78; p = 0.03), which was the primary endpoint of the trial. After a median follow-up period of 34.1 months, median survival was 4.1 months longer with sipuleucel-T than placebo (25.8 vs 21.7 months). There was no significant between-group difference for the median time to objective disease progression (a secondary endpoint). Almost all patients treated with sipuleucel-T in clinical trials reported an adverse event, although these were mild or moderate in severity (grade 1 or 2) in most patients. The most common adverse events (e.g. infusion-related events, such as chills and fever) generally occurred within the first day after administration of sipuleucel-T and resolved within 2 days.

Written by:
Plosker GL. Are you the author?

Reference: Drugs. 2011 Jan 1;71(1):101-8.
doi: 10.2165/11206840-000000000-00000

PubMed Abstract
PMID: 21175243

RPP, the most cost-effective treatment for OCPCa.

Written by Lynda Coghlan
Wednesday, 02 February 2011 07:52
Urology Centre, Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.

sashurol@gmail.com

With the increasing prevalence of prostate cancer and evolving methods for the definitive treatment of OCPCa, health economic analyses will be critically important, albeit difficult to carry out. Preliminary studies point to RPP as the most cost-effective treatment for OCPCa. The quickest postoperative recovery, in experienced hands, occurs in RARP and RPP, with ORPP having a slightly, but statistically in significant, shorter hospital stay. It should be stressed that initial treatment costs are not the only important factor in healthcare costs. Readmission for early and late complications and the loss of productivity resulting from variation in time to return to work, need also to be considered. Loss of productivity may also vary in cost between different institutions and countries depending upon the proportion of patients employed. Further large-scale multicentre studies are necessary to assess this.

Written by:
Kommu SS, Eden CG, Luscombe CJ, Golash A, Persad RA. Are you the author?

Reference: BJU Int. 2011 Jan;107(1):1-3.
doi: 10.1111/j.1464-410X.2010.09885.x

PubMed Abstract
PMID: 21176067

UroToday.com Prostate Cancer Section

Active Surveillance & Ffocal Therapy Treat PCa

Written by Lynda Coghlan
Thursday, 03 February 2011 03:12
USC Institute of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

Active surveillance and focal therapy for prostate cancer have been proposed as treatment alternatives for prostate cancer. In this review, we track the emerging technologies that will support the viability of such management strategies.

Widespread prostate-specific antigen (PSA) testing and extended prostate biopsy practice patterns have resulted in a significant increase in the diagnosis of low-risk prostate cancer. As most low-risk prostate cancers may not require radical treatment, alternatives for appropriately selected patients have been proposed and implemented - namely, active surveillance and focal therapy. Both alternatives to radical therapy require accurate mapping and precise targeting of lesions within the prostate, for which current technological shortfalls limit their clinical utility. The emerging tools that will help overcome these challenges include refined imaging modalities, three-dimensional modeling for planning and tracking intervention, elastic fusion image technology, and automated mechanical delivery of the intervention needle.

Current prostate biopsy technologies have largely advanced as separate entities. Further refinement of these innovations continue, but the ultimate challenge will be integrating them into one comprehensive platform.

Written by:
Ukimura O, Hung AJ, Gill IS. Are you the author?
Reference: Curr Opin Urol. 2011 Mar;21(2):115-20.
PubMed Abstract
PMID: 21178631
UroToday.com Prostate Cancer Section



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