In addition to diagnostic scanning, there are several other tests that might be considered for selected patients to gain a better understanding of the biology and location of their cancer. These include a variety of blood tests, urine markers and invasive procedures.
Prostatic Acid Phosphatase (PAP)
PAP is an enzyme that may be released into the blood by the prostate or prostate cancer but is also produced by other tissue. It is not as specific as PSA and has mostly been replaced but PAP can be valuable for patients with higher Gleason grade cancer that might not produce a lot of PSA. Moul, et al  reported “PAP was not of value for predicting organ-confined PC or positive margins but was useful for predicting the biochemical failure. The Kaplan-Meier disease-free survival rate at 4 years was 78.8% for men with PAP less than 3 ng/ml and 38.8% for those with a PAP of 3 ng/ml or greater.”
1. Moul JW, Connelly RR, et al. The Contemporary Value of Pretreatment Prostatic Acid Phosphatase to Predict Pathological Stage and Recurrence in Radical Prostatectomy Cases. J Urology 159, 935-940,1998
For monitoring treatment in advanced prostate cancer, Steineck et al  evaluated 107 patients with androgen-independent prostate cancer (AIPC) who had been treated on seven different protocols at the Memorial Sloan-Kettering Cancer Center. For PAP and PSA, a minimum 50% or 80% decrease from baseline documented on three separate occasions a minimum of six weeks apart. The authors concluded that post-therapy declines in PSA and PAP represent reproducible endpoints for clinical trials in AIPC. The requirement of a repeated and parallel decline in both markers may improve the results observed by monitoring declines in PSA alone.
2. Steineck G, Kelly WK, et al. Acid phosphatase: defining a role in androgen-independent prostate cancer. Urology. 1996 May;47(5):719-26.
Gleason grades of 4 and 5 may not release much PSA into the blood stream. Along with PAP, three neuroendocrine biomarkers: CEA (carcinoembryonic acid), NSE (Neuron-specific enolase) CGA (chromogranin A) may help to uncover a more aggressive disease pattern and could be helpful in monitoring the course of treatment. While the initial values may be in the normal range, the change over time may be significant for evaluating your progress. When a progressive increase in any of these biomarkers is documented, there is a probability of mutated aggressive prostate cancer. For a detailed discussion, see A Primer on Prostate Cancer, The Empowered Patient's Guide by Strum & Pogliano.
Circulating Tumor Cells (CTC)
The CellSearch® Circulating Tumor Cell (CTC) Test from Veridex is a simple blood test that captures and assesses CTCs to determine the prognosis of patients with metastatic breast, colorectal or prostate cancer at any time. The test offers an objective, quantitative, real-time reading of tumor information so that oncologists can provide optimum care for their patients.
See Veridex website for additional information.
Prostate CAncer gene 3 (PCA3) is a new gene-based test carried out on a urine sample. PCA3 is highly specific to prostate cancer and, therefore, in contrast to PSA, not increased by conditions such as benign enlargement or inflammation of the prostate. The PCA3 (uPM3) is a urine test that predicts cancer in prostate biopsy with better accuracy than prostate specific antigen (PSA). Patients who receive the PCA3 test undergo an “attentive” digital rectal examination by a urologist, a standard procedure in prostate cancer detection. This exam causes cells from the patient's prostate to be shed into the urine, and the urine sample, containing the released cells, is sent to a specialty laboratory to be tested for genetic expression of the PCA3 gene. If the sample is positive for PCA3, then the patient has a significant likelihood of having prostate cancer. It is also useful in monitoring the disease during Active Surveillance. See our paper: PCA3: A Genetic Marker of Prostate Cancer
Also see: PCA3.org
Bone Resorption Urine Markers
Elevated bone resorption urine markers such as Pyrilinks-D (deoxypyridinoline or Dpd) and N-telopeptides have been shown to be associated with distant metastasis. These markers indicate the rate of bone breakdown (or resorption). The Pyrilinks-D or Dpd test is an inexpensive laboratory examination that measures a fragment of the bone matrix that is excreted into the urine. In situations of excessive bone resorption or breakdown, the Dpd is elevated. In men, this is greater than 5.4 nmoL Dpd per nmoL urine creatinine. Excessive bone resorption at diagnosis is associated with a greater risk of occult metastatic spread of PC. Takeuchi reported  that serial measurement of urinary pyridinoline and deoxypyridinoline was correlated with a positive response to treatment (decreased) and with clinical progression of disease (increased) before detection of new bone lesions by bone scan.
3. Takeuchi S, Arai K, et al. Urinary pyridinoline and deoxypyridinoline as potential markers of bone metastasis in patients with prostate cancer. J Urol. 1996 Nov;156(5):1691-5.
Prostate Px+ utilizes patient biopsy tissue to provide a new perspective that can enable more-informed decisions at diagnosis. Prostate Px+ assesses prostate cancer risk by examining tissue structure and molecular biomarkers to provide each patient with an objective, personalized risk assessment. Prostate Px+ combines existing clinical information with advanced molecular and cellular analysis of the cancer, enabling a deeper, and more comprehensive assessment of risk than traditional methods that rely exclusively on Gleason score or PSA. Upon completion of the test, a personalized report is sent to the patient’s physician for discussion with the patient. Each report provides a detailed risk analysis of the patient’s tumor, as well as a risk score for that patient between 1 and 100. The lower the patient’s Px+ SCORE, the lower their risk for serious disease progression. The test was developed by Aureon.
Pelvic Lymph Node Dissection
With a diagnosis of potentially high-risk prostate cancer, there is increased risk of spread to the pelvic lymph nodes. It may be suggested to sample these lymph nodes for review by a Pathologist before proceeding with a treatment or a treatment decision.
This may be done as the initial step in a radical prostatectomy. The lymph nodes are tested in the lab while you are still under anesthesia. The results will help the surgeon decide whether or not to go on with the surgery. It can be a separate procedure prior to selecting a local treatment. This is most commonly done using laparoscopy. A long, thin tube with a small camera on the end is put into the abdomen through a small incision. Other incisions are made to put in long instruments to remove lymph nodes. Recovery usually takes only 1 or 2 days and there is very little scarring from this operation.
Lymph nodes may also be sampled by fine needle aspiration (FNA). The doctor uses the CT scan to guide a long, thin needle through the skin and into the lymph nodes. This is an outpatient procedure and you can go home a few hours later.
Page updated 8/1/11