Expectations of Survival for HRPCa Patients
 

Introduction

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 mortality. 

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 HRPC disease. This is the stage of the disease that nearly 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 10 years.

Background

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 trials.

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 significant.

(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 Investigators, Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer, 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).

Sequential Chemotherapy
 

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 other information:

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 months(8).

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 HRPC 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 newer)

• D2=metastatic disease in bone and/or other organs.

• D3= HRPC disease.