Quality of life three years after diagnosis of localised prostate cancer: population based cohort study

We read with interest the paper by Smith and colleagues concerning
quality of life following diagnosis and treatment of localised prostate
cancer 1. The findings, however, are neither new nor unexpected with
landmark papers within the last decade demonstrating the detrimental
impact of radical prostatectomy and external beam radiotherapy on sexual,
urinary and bowel function 2 3.

Uro-oncologists have not been deaf to these calls. Much resource has
gone into refining both radiotherapeutic and surgical approaches to care.
For instance, the 2-dimensional planning employed in earlier radiotherapy
regimens has been largely replaced by 3-dimensional conformal radiotherapy
and Intensity Modulated Radiotherapy (IMRT). Some are advocating proton
therapy as a solution to the toxicity problem. Surgical technique has also
undergone dramatic change with more patients undergoing minimal access
prostatectomy with or without the assistance of robotic systems 6. These
novel techniques can be more time consuming and more expensive to
undertake 7-8.

The key question is: have they improved the toxicity of the
interventions? The answer appears to be that the increased specification
has not resulted in the benefits that might have been expected.

A recent study found that long-term incontinence and erectile
dysfunction was significantly higher following minimally invasive surgery
when compared to conventional open surgery 6. In addition, the long-term
treatment-associated gastrointestinal and genitourinary toxicity following
radiotherapy still remains as high as 12%, even with the use of IMRT 9.

The toxicity of prostate cancer treatment should also be considered
in light of the knowledge that many men with localised prostate cancer are
at risk of being over-treated for their disease. Evidence for this comes
from the recent European Prostate Screening Trial that identified that
1410 men need to be screened and 48 diagnosed and treated in order to save
one life over a 10 year period10.

Could it be that we have reached the limits of tolerability when
whole gland radical therapy is attempted? It would seem so as
technological advances are producing little gain at increased costs.

Is it time to consider an alternative strategy? In nearly all other
surgical treatment of cancer there has been a move away from whole organ
treatment to organ preservation. This was seen in breast cancer many
years ago 11 and more recently has become common place for other cancers
such as kidney cancer where partial nephrectomy is advocated for small
renal tumours 12.

There are early signs that such an approach could be considered in a
small organ such as the prostate 13-14. The move away from whole gland
treatment has been termed focal therapy 15-16 and appears, on face value
at least, to be tenable as most prostate cancers occupy only 5% of the
prostate volume. What is required however is the accurate
characterisation and localisation of the cancer.

Imaging is currently used to detect and direct biopsy in the vast
majority of solid organ cancers. Prostate cancer is unique in that the
diagnostic test - transrectal ultrasound guided prostate biopsy - uses
chance to rule in and rule out cancer. This is because grey-scale
ultrasound - used to guide needle placement during transrectal prostate
biopsy, is unable to accurately detect the presence of cancer 17. In
addition, such random deployment of the needle has lead to over-diagnosis
of clinically insignificant cancer foci. . If focal therapy is to be
adopted for localised prostate cancer treatment, a shift in the way we
currently diagnose and characterise prostate cancer is required.
Multifunctional MRI and advanced ultrasound techniques have demonstrated
promising results in this respect.

There is a strong argument to prioritise focal therapy for formal
evaluation as it is the only strategy currently on the table that might
result in an acceptable balance of harms and benefits for most patients.
Moreover, it is attractive from a resource allocation perspective as the
intervention can be done on a day case basis with technologies that are
widely available and used across disciplines.

References:

1. Smith DP, King MT, Egger S, Berry MP, Stricker PD, Cozzi P, Ward
J, O'Connell DL, Armstrong BK. Quality of life three years after diagnosis
of localised prostate cancer: population based cohort study. BMJ. 2009 Nov
27;339:b4817.

2. Steineck G, Helgesen F, Adolfsson J, Dickman PW, Johansson JE,
Norlén BJ,
Holmberg L; Scandinavian Prostatic Cancer Group Study Number 4.Quality of
life after radical prostatectomy or watchful waiting. N Engl J Med. 2002
Sep 12;347(11):790-6.

3. Madalinska JB, Essink-Bot ML, de Koning HJ, Kirkels WJ, van der
Maas PJ, Schröder FH. Health-related quality-of-life effects of radical
prostatectomy and primary radiotherapy for screen-detected or clinically
diagnosed localized prostate cancer. J Clin Oncol. 2001 Mar 15;19(6):1619-
28.

4. Cassileth BR, Soloway MS, Vogelzang NJ, Chou JM, Schellhammer PD
et al. Quality of Life and psychosocial status in stage D prostate cancer.
Zoladex Prostate Cancer Study group. Qual of Life Res 1992:1: 323-9

5. Kintzel P, Chase S, Schultz L, O’Rourke T. Increased risk of
metabolic syndrome, diabetes mellitus and cardiovascular disease in
receiving androgen suppression therapy for prostate cancer.
Pharmacotherapy 2008: 28(12): 1511-1522.

6. Hu JC, Gu X, Lipsitz SR, Barry MJ, D'Amico AV, Weinberg AC,
Keating NL.Comparative effectiveness of minimally invasive vs open radical
prostatectomy. JAMA. 2009 Oct 14;302(14):1557-64.

7. Bolenz C, Gupta A, Hotze T, Ho R, Cadeddu JA, Roehrborn CG, Lotan
Y. Cost Comparison of Robotic, Laparoscopic, and Open Radical
Prostatectomy for Prostate Cancer. Eur Urol. 2009 Nov 11.

8. Zietman AL. The Titanic and the Iceberg: prostate proton therapy
and health care economics. J Clin Oncol. 2007 Aug 20;25(24):3565-6.)

9. Martin JM, Bayley A, Bristow R, Chung P, Gospodarowicz M, Menard
C, Milosevic M, Rosewall T, Warde PR, Catton CN. Image guided dose
escalated prostate radiotherapy: still room to improve. Radiat Oncol. 2009
Nov 3;4:50. Erratum in: Radiat Oncol. 2009;4:65.

10. Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen
V, Kwiatkowski M, Lujan M, Lilja H, Zappa M, Denis LJ, Recker F, Berenguer
A, Määttänen L, Bangma CH, Aus G, Villers A, Rebillard X, van der Kwast T,
Blijenberg BG, Moss SM, de Koning HJ, Auvinen A; ERSPC Investigators
Screening and prostate-cancer mortality in a randomized European study. N
Engl J Med. 2009 Mar 26;360(13):1320-8. Epub 2009 Mar 18.

11. Jacobson J, Danforth D, Cowan K, D’Angelo B, Steinberg S, Pierce
L et al. Ten-year results of a comparison of conservation with mastectomy
in the treatment of stage I and II breast cancer. N Engl J Med. 1995 Apr
6:332 (14): 907-11

12. Breau RH, Crispen PL, Jimenez RE, Lohse CM, Blute ML, Leibovich
BC. Outcome of Stage T2 or Greater Renal Cell Cancer Treated With Partial
Nephrectomy.J Urol. 2010 Jan 16.

13. Onik G, Vaughan D, Lotenfoe R, Dineen M, Brady J. The “male
lumpectomy”. Focal therapy for prostate cancer using cryotherapy results
in 48 patients with at least 2-year follow-up Urol Oncol. 2008 26 (5): 500
-5

14. Ahmed HU, Moore C, Emberton M. Minimally-invasive technologies in
uro-oncology: the role of cryotherapy, HIFU and photodynamic therapy in
whole gland and focal therapy of localised prostate cancer. Surg Oncol.
2009 Sep;18(3):219-32. Epub 2009 Mar 5. Review.

15. Onik G, Narayan P, Vaughan D,Brunelle R. Focal “nerve-sparing”
cryosurgery for treatment of primary prostate cancer> a new approach to
preserving potency. Urology. 2002 60 (1):109-14

16. Eggener SE, Scardino PT, Carroll PR, Zelefsky MJ, Sartor O,
Hricak H, Wheeler TM, Fine SW, Trachtenberg J, Rubin MA, Ohori M, Kuroiwa
K, Rossignol M, Abenhaim L; International Task Force on Prostate Cancer
and the Focal Lesion Paradigm. Focal therapy for localized prostate
cancer: a critical appraisal of rationale and modalities. J Urol. 2007
Dec;178(6):2260-7. Epub 2007 Oct 15. Review.

17. Sedelaar JP, De La Rosette JJ, Beerlage HP, Wijkstra H, Debruyne
FM, Aarnink RG. Transrectal ultrasound imaging of the prostate: review and
perspectives of recent developments. Prostate Cancer Prostatic Dis. 1999
Dec;2(5/6):241-252

Competing interests:
Ahmed, Moore and Emberton are lead clinicians in 3 NCRI clinical trials evaluating the role of focal therapy for prostate cancer treatment