Expectations of Survival for HRPCa Patients
As patients, we would all like to survive as long as
possible with the best quality of life (QOL). We do know that everyone
dies at some time, but HRPCa patients are faced with a greater certainty of our
Patients ask questions such as "When I became hormone
refractory three weeks ago my oncologist said there is no chemotherapy that will
significantly extend survival time. If that is true, why should I suffer the
toxic effects of the drugs?" Read on to get a better feel for
what increased survival means -- time-wise.
Many papers are published that start out with the statement that men
diagnosed with HRPCa have a poor prognosis with a median survival of less
than 12 months (sometimes 18 months) for symptomatic patients. In the pre-PSA
era, this may well have been true. Now many men fit the definition of HRPCa with only a rising PSA and are asymptomatic.
You should also know that there is no cure for HRPCa disease. This is the
stage of the disease that over 30,000 men die from
each year in the USA.
Just remember, the median means half die earlier than the median and half survive longer.
See Jay Gould's essay,
The Median Isn't the Message.
A paper by JC Cheville et al in Cancer 2002 Sept 1;95(5):1028-36 illustrates
this: In this study of 68 pts (all underwent surgery for metastatic prostate
cancer to the bone to stabilize a pathologic fracture or impending fracture.
Their results were the average time from surgery to death was 1.5 years, ±
1.9 years, ranging from 0 days to 10 years, with a median of 1 year. So
looking at only the 1 year would be misleading if that patient survived for
There is no survival benefit if you compare taking mitoxantrone/prednisone relative
to taking prednisone alone. These trials were not looking for survival
as much as just palliation of symptoms. The men on mitoxantrone/prednisone
felt much better than those on prednisone alone. They were small
If you compare taxotere/prednisone vs mitoxantrone/prednisone you find a
significant survival benefit for taxotere/prednisone of 2.5 months (1). That may not sound like much, but the change amounts to 24%
and it is
(1)Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S,
Theodore C, James ND, Turesson I, Rosenthal MA, Eisenberger MA; TAX 327
Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced
N Engl J Med. 2004 Oct 7;351(15):1502-12.
In reality, few people do only one chemotherapy. You do sequential
chemotherapy of which taxotere /prednisone is one, then
mitoxantrone/prednisone (with an adder of HDK/HC). The use of
intermittent chemo is similar to the off period of those doing intermittent
hormone therapy -- a time for recovery from chemotherapy. Furthermore,
combining multiple secondary hormonal manipulations plus
sequential/intermittent chemotherapy allows the possibility of longer
survival (vs just palliative treatment -- again, there is no trial data for this).
A thorough exploration of this category, requires a web page just devoted to
this subject. See chemo sequences and also
sequencing chemo (Aishman). Here's some
Re-exposure to taxotere(2nd line chemo) - 32% PSA response rate, median
overall survival of 9.6 months, median progression-free survival of 8.0
Re-exposure to taxotere plus high dose calcitriol had a PSA response rate of
31% and median survival of 9.3 months (9). Seven patients (27%) had a stable
PSA level for ≥ 12 weeks.Treatment cycles consisted of calcitriol (32 microg
orally as 0.5 microg tablets) on day 1 and docetaxel (30 mg/m(2)
intravenous) on day 2, administered for six consecutive weeks followed by a
2-week rest interval for a maximum of 24 cycles.
Taxotere (36mg/m2) 3 of 4 weeks, given with high dose calcitriol(DN-101, 45
mcg)(10) in an intermittent manner had PSA responses of 45.5%. A total of 250
patients were randomized 1:1. Overall, 18% of patients (20% in the high-dose
calcitriol group and 16% in the placebo group) entered the intermittent
chemotherapy arm. The median duration of the first chemotherapy holiday was
18 weeks (range, 4-70 weeks).
(10)On resumption of treatment after the first
holiday, 45.5% of evaluable patients responded with a ≥50% reduction in
serum PSA from their postholiday baseline, 45.5% met the criteria for stable
PSA for at least 12 weeks, and 9.1% of patients developed disease
progression. The paper indicates that 13 patients had taken ≥ 2 chemotherapy
holidays and 10 patients had completed their second chemo holiday. So, even
for a third line chemo, this combination works for some. Whether or not this
leads to longer survival of these particular patients isn't known, but one
would like to think that it might.
Nakabayashi et al (11) found that patients who failed
first line taxotere, also failed a second attempt with the taxotere/carboplatin
combination. Nakabayashi's paper is quite confusing on this, so I refer you
to the paper itself for more details. Other combinations such as taxotere
and capecitabine might work better.
Recent Studies on Survival of HRPCa Patients
Recently, a couple of papers/studies shed more light on the survival
question. Oefelein MG et al (2) survival result was:
Median Survival -- 40 months if initially staged with skeletal metastasis
and 68 months (5.5 years!) if initially staged without skeletal metastasis.
These were calculated from the time of first PSA increase while having
castrate levels of testosterone.
(2) Oefelein MG et al, "Survival of
Patients With Hormone Refractory Prostate Cancer in the Prostate Specific
Antigen Era, The Journal of Urology, Vol. 171, 1525-1528, April 2004.
Another study is from the AUA Annual Meeting 2004(3).
This paper contains several interesting statements -- including an
outcome with Radical Prostatectomy vs Radiation Therapy:
Definitions(this is an older system -- the TNM staging system is
Data was retrieved from the DoD-CPDR National Database active at 9
major US Military medical treatment facilities: Of 10,500 prostate cancer
patients enrolled, 398 men (3.8% overall) were classified with stage D3(HRPC) and
their results are what is discussed in this paper. HRPC/D3 disease was defined as two rises in
PSA level while on traditional HT.
The HRPC/D3 patients came from three groups (total 398
(group 1) patients who had a rising PSA while on HT but
before D2 disease - 178 (44.7%);
(group 2) patients who had progressive D2 disease - 139
(group 3) patients who initially had new D2 disease - 81
Disease-specific survival was evaluated by Kaplan-Meier methods.
The overall 5-year survival from (the PSA-based definition of) D3
was 44.8% illustrating the profound lead-time of PSA in the definition of HRPCa.
5-year survival for group 1 55.6%
and for group 2 5-year survival was 29.1%(p<0.0001) illustrating that PSA-Only HRPC
has a better outcome than more traditional HRPC.
The authors also found that men who
underwent radical prostatectomy(RP) and developed D3 disease had a 5 year
survival during this stage of 57.8% compared to only 37.8% for men who
underwent primary radiotherapy (XRT)(p=0.001).
(3)Yongmei Chen, Judd W Moul, Leon Sun, David G McLeod, Christopher L Amling,
Timothy F Donahue, Leo Kusuda, Wade J Sexton, Keith J O'Reilly, Javier
Hernandez, Andrew Chung, Karen Smith, Bethesda, MD; Contemporary Experience
With Hormone Refractory Prostate Cancer (HRPC - Stage D3) in the PSA-Era:
Report from the DOD CDPR National Database, AUA 2004,
Other Studies Related to Survival
Halabi et al (4), developed a nice nomogram that allows one to estimate
12-month and 24-month survival. The paper is free on-line at
Here also is
a paragraph from PCF's Report to the Nation on Prostate Cancer 2004;
Androgen Deprivation Therapy for PCa which relates to survival. In
contrast to (2) and (3), this paragraph paints a rather dismal survival for
HRPC patients. In the era of PSA, this is obviously changing (see 2 and 3
above). Note that these are median numbers.
prostate cancer is initially responsive to hormone
manipulation, the responsiveness of tumor cells to ADT in patients
with metastatic disease begins to wane rather quickly,
with a median time to disease progression of less than 2
years.[5,6] Secondary hormonal manipulation is still
this population because androgen-independent prostate
cancer (AIPC) remains somewhat responsive to
testosterone. Unfortunately, none of the available methods is curative,
and the median survival of patients with AIPC is 12-16 months
from the time that androgen independence is
established. Additional therapeutic options should therefore be explored
by the multidisciplinary care team."
At ASCO 2009, a
Danish group(7) retrospectively reviewed 8 years worth of data to determine
the significance of bone metastases and SREs (skeletal-related events) on survival.
They estimated the
incidence of bone metastases following diagnosis and the subsequent
occurrence of SREs which are defined as radiation and/or surgery to the
bone, fracture and spinal cord compression. The 23,087 patients were divided
into 3 subgroups and their survival compared -- no bone metastases, bone
metastases, and bone metastases with SREs.
||One Yr Survival
||1 Yr Mortality Rate compared to no bone mets.
|No bone metastases
|Bone metastases and no SREs
Bone metastases and at
least 1 SRE
Radiation to the bone was
most frequent SRE.
Less than 1% of prostate cancer patients who
developed bone metastases and suffered any SRE survived beyond five years.
summarize. Survival duration: No bone mets > bone mets > bone mets and SRE.
(4) Susan Halabi,
Eric J. Small, Philip W. Kantoff, Michael W. Kattan, Ellen B. Kaplan, Nancy
A. Dawson, Ellis G. Levine, Brent A. Blumenstein, Nicholas J. Vogelzang, Prognostic
Model for Predicting Survival in Men With Hormone-Refractory Metastatic
Prostate Cancer, Journal of Clinical Oncology, Vol 21, Issue 7 (April), 2003: 1232-1237.
CL, Gumerlock PH, Meyers FJ, Lara PN Jr. Current strategies in the
management of hormone refractory prostate cancer. Cancer Treat Rev.
SR, Isaacs JT. Development of prostate cancer treatment: the good
news. Prostate. 2004;58:211-224.
(7) J. P. Fryzek, K. Cetin, M. Nørgaard, A. Ø. Jensen,
J. Jacobsen, H. T. Sørensen, The prognostic significance of bone metastases and
skeletal-related events (SREs) in prostate cancer survival: A
population-based historical cohort study in Denmark (1999-2007), J Clin Oncol 27:15s, 2009 (suppl; abstract
(8) B. Jankovic, E.
Beardsley, K. N. Chi, Rechallenge with docetaxel as second-line chemotherapy
in patients with metastatic hormone refractory prostate cancer (HRPC) after
previous docetaxel: A population based analysis, 2008 Genitourinary Cancers
Symposium, abstract #196.
(9) Petrioli R,
Pascucci A, Francini E, Marsili S, Sciandivasci A, De Rubertis G, Barbanti
G, Manganelli A, Salvestrini F, Francini G., Weekly high-dose calcitriol and
docetaxel in patients with metastatic hormone-refractory prostate cancer
previously exposed to docetaxel, BJU Int. 2007 Oct;100(4):775-9. Epub 2007
(10) Beer TM, Ryan
CW, Venner PM, Petrylak DP, Chatta GS, Ruether JD, Chi KN, Young J, Henner
WD; Intermittent chemotherapy in patients with metastatic
androgen-independent prostate cancer: results from ASCENT, a double-blinded,
randomized comparison of high-dose calcitriol plus docetaxel with placebo
plus docetaxel, ASCENT(AIPC Study of Calcitriol ENhancing Taxotere)
Investigators. Cancer. 2008 Jan 15;112(2):326-30.
(11) Nakabayashi M,
Sartor O, Jacobus S, Regan MM, McKearn D, Ross RW, Kantoff PW, Taplin ME, Oh
WK, Response to docetaxel/carboplatin-based chemotherapy as first- and
second-line therapy in patients with metastatic hormone-refractory prostate
cancer, BJU Int. 2008 Feb;101(3):308-12.
Howard Hansen 12 Dec 2008; Updated 21 January 2010.