Hi, I don't know how to copy URL's but did manage to copy the message (see below).
It turned out that my husband has a very agressive second primary tumor, somewhere in the GI track. It has already spread to the liver. The situation is rather grim. Although it's a long shot, we'll probably start chemo tomorrow. These are trying times.
Dutchy,
Chemotherapy at this point would probably be the best bet. There is a
possibility that he has small cell prostate cancer given his spread to the
liver and lungs (usually there is a mix of "regular" hrpc disease and scpc.)
A combination of taxotere, carboplatin and emcyt might be used; usually a
cisplatin (carboplatin is an easier on the patient variant of cisplatin) is
used along with some other chemotherapy.
You don't give his Gleason Score, but if it was 8 or 9 or 10 then those very
undifferentiated prostate cancer often do not produce any PSA or only little
PSA. That doesn't jibe with his June 2007 PSA of 2000, however, so it might
be the case that the cancer has mutated into a different form or there was a
good mix of low Gleason score cancer (that produced a lot of PSA) and SCPC.
The hormone therapy combination of Lupron and Casodex removed the "regular"
HRPC disease, leaving mainly SCPC (realize that I am speculating on all this
as there isn't data given by you to support much beyond speculation. )
The SCPC, again, doesn't product much, if any PSA.
There is a whole body of literature on low PSA levels and disease
progression. Here are 3 abstracts of papers covering this aspect of HRPC
disease:
1. Eur Urol. 2000 Sep;38(3):250- 4.
Low PSA metastatic androgen- independent prostate cancer.Sella A, Konichezky
M, Flex D, Sulkes A, Baniel J.
Genitourinary Medical Oncology Unit and Department of Oncology, Rabin
Medical Center, Beilinson Campus, Petah Tikva, and Sackler Faculty of
Medicine, Tel Aviv University, Tel Aviv, Israel. avisella@netvision. net.il
OBJECTIVES: To describe the clinical parameters of low PSA, progressive
metastatic androgen-independen t prostate cancer. METHODS: From April 1995 to
May 1999, we selected 18 patients with clinically progressive
androgen-independen t prostate cancer and low PSA (</=10 ng/ml). Patients
received cisplatin-based therapy. Specimens from the primary tumor were
reviewed and neuroendocrine differentiation was determined with
chromogranin- A and neuron-specific enolase immunocytochemical staining.
RESULTS: The median initial PSA level was 1.6 ng/ml (0-9.5). Each patient
demonstrated elevation of at least one of the following markers:
carcinoembryonic antigen, CA 19-9, CA15-3 and CA 125 CA. Metastases involved
bone in 11 patients (61.1%) - 5 (27.7%) blastic, 2 (11.1%) lytic, and 4
(22.2%) combined - liver in 10 patients (55.5%), lymph nodes in 8 (44.4%),
and lung in 6 (33.3%); solitary sites as orbit, skin and spleen were noted
as well. A prostatic pelvic mass was detected in 13 patients (72.2%). Of the
12 patients who consented to chemotherapy, 8 (66.6%) achieved an objective
response (95% CI, 34. 8-90%), including 1 patient with complete response.
Hematoxylin and eosin evaluation revealed two major groups: neuroendocrine
tumors, either pure small cell cancer in 6 patients (37.5%) or combined
small cell cancer and adenocarcinoma in 8 (50%), and predominant poorly
differentiated prostate cancer in 2 (12.5%). Neuroendocrine immunoreactivity
was detected in all the specimens. CONCLUSIONS: Progressive
androgen-independen t prostate cancer with low serum PSA is characterized by
visceral metastases, high proportion of lytic bone disease, sensitivity to
cisplatin-based chemotherapy, and histological features of small cell or
poorly differentiated prostate cancer. In this subgroup of patients,
selection of the therapeutic approach can be based on clinical parameters.
The rise of the serum markers may aid in the diagnosis and follow-up of
these patients.
PMID: 10940696
2. Cancer. 2007 Jan 15;109(2):198- 204.
Prostate cancer progression in the presence of undetectable or low serum
prostate-specific antigen level.Leibovici D, Spiess PE, Agarwal PK, Tu SM,
Pettaway CA, Hitzhusen K, Millikan RE, Pisters LL.
Department of Urology, The University of Texas M. D. Anderson Cancer Center,
Houston, Texas 77030, USA.
BACKGROUND: The serum prostate-specific antigen (PSA) level after definitive
treatment for prostate cancer (PC) is a powerful predictor of outcome.
Occasionally, PC progression can occur despite low or undetectable PSA
levels. The authors report on the clinical and pathologic characteristics of
patients who experienced PC progression with undetectable or low PSA levels.
METHODS: From an electronic database of all patients with PC who were
treated at The University of Texas M. D. Anderson Cancer Center between 1999
and 2004, a group of 46 patients was identified who had progression to
metastatic PC detected with concomitant PSA levels from 0.1 ng/mL to 2
ng/mL. Patient charts were reviewed for tumor stage, Gleason score,
pretreatment PSA level, and the presence of atypical histologic variants
(ie, ductal, sarcomatoid, or small cell cancers). The nadir PSA level after
treatment and the PSA level at the time metastatic PC was detected were
determined. The patients were followed semiannually, and imaging studies
were obtained at the discretion of treating physicians. The sites of
metastasis and histologic confirmation were reported when available.
RESULTS: Twenty-three of 46 patients underwent radical prostatectomy, 11
patients received radiation therapy, and 12 received hormone treatment as
their initial form of therapy. Progression to metastatic disease with
concomitant, undetectable PSA levels occurred in 10 patients, including 3
patients who had not received treatment with hormones. The sites of
metastasis included bone (n = 35 patients), liver (n = 7 patients),
retroperitoneal lymph nodes (n = 5 patients), lungs (n = 4 patients), and
brain (n = 1 patient). Aggressive and locally advanced PC were common
features in these patients: Eighty-five percent had Gleason scores >or=7,
63% had clinical T3 or T4 tumors, and 41% had pretreatment PSA levels >10
ng/mL. Atypical histologic variants were observed in 21 patients (46%) and
in 8 of 10 patients who progressed with undetectable PSA levels. In 10
patients (22%), metastasis were detected in the presence of an undetectable
PSA level. Eight of those patients had small cell carcinoma. In 19 patients
(41%), progression to metastasis occurred without any increase in their PSA
from the nadir level. Thirty-one patients (67%) were asymptomatic at the
time metastasis was detected, and the detection of metastasis in these
patients occurred only because of routine imaging studies. CONCLUSIONS:
Progression of PC may occur despite undetectable or low PSA levels. Complete
physical evaluation and imaging studies may be indicated in the surveillance
of patients with high-grade, locally advanced tumors, especially when
atypical histologic variants are present. PMID: 17171704
There is also this study combining DES and Taxotere as a possible treatment
-- how effective it is for your husbands disease isn't apparent.
Cancer. 2007 Sep 1;110(5):996- 1002. Links
Diethylstilbestrol and docetaxel: a Phase II study of tubulin active agents
in patients with metastatic, androgen-independen t prostate cancer.Montgomery
RB, Nelson PS, Lin D, Ryan CW, Garzotto M, Beer TM.
Department of Medicine, Veterans Affairs Puget Sound Health Care System
(VAPSHCS), and University of Washington School of Medicine, Seattle, WA
98108, USA.
[email protected] on.edu
BACKGROUND: The addition of diethylstilbestrol to docetaxel modified tubulin
composition and improved the response of prostate cancer to chemotherapy in
preclinical models. An attempt was made to recapitulate the observations in
a clinical trial. METHODS: Twenty-nine patients with progressive,
metastatic, chemotherapy- naive androgen-independen t prostate cancer were
treated with diethylstilbestrol 1 mg daily and 5 mg on the day before
docetaxel and docetaxel 36 mg/m(2) intravenously weekly for 3 weeks of a
4-week cycle. Prophylactic anticoagulation was used in all patients.
Patients were assessed by prostate-specific antigen (PSA) monthly and
computed tomography (CT) and bone scans every 3 cycles. The Response
Evaluation Criteria in Solid Tumors (RECIST) criteria and PSA decline by
>50% maintained for 4 weeks were used to assess activity. RESULTS: The
median age was 68 years (range, 56-84 years), Southwest Oncology Group
performance status 0 (score range, 0-2), alkaline phosphatase 120 U/L
(range, 49-523), hemoglobin (Hgb) 12.6 g/dL (range, 9.2-16.3), PSA 66 ng/dL
(range, 4-1962). The median number of cycles administered was 6. Soft tissue
metastases were present in 51% of patients and bone metastases in 93%.
Twenty-nine patients are evaluable for response. Of these, 20 patients (69%,
95% confidence interval [CI], 49%-85%) had a PSA decline of >50% and the PSA
declined by >90% in 12 patients (41%, 95% CI, 23.1%-58.9%) . Of 15 patients
with measurable disease, 6 (40%, 95% CI, 23.5%-61%) had a partial response.
Median time to progression was 6 months (range, 3-19 months). Fifteen
patients (51%) suffered grade 3/4 toxicity. Two patients died of causes
unrelated to therapy and another died from a steroid-induced ulcer. Six
patients developed thrombosis and of those tested 75% had Factor V
mutations. Pretreatment PSA, performance status, Hgb, and alkaline
phosphatase had no impact on the likelihood of response. CONCLUSIONS: The
combination of diethylstilbestrol and docetaxel produces a significant level
of activity, measured by PSA decline and measurable disease response rate,
and except for venous thrombosis the toxicity appears similar to that seen
with docetaxel plus prednisone. These results suggest that tubulin
modulation with diethylstilbestrol may improve the therapeutic efficacy of
docetaxel and the combination is worthy of further study.
Your specific questions:
No it doesn't happen a lot, see the abstracts above for some idea of the
frequency of this happening.
There is of course, PSA, but do CgA, NSE, CEA, PAP.
Do frequent scans -- CT or MRI and Bone Scan to monitor/check for
progression.
Taxotere (and this would probably be better if carboplatin and emcyt were
also included) might attack the liver metastases. There are other possible
choices as well. I would move ahead with treatment as quickly as you can.
Take care,
Howard