Surgery (Austin & Northern Health) - Theses
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ItemPrognostic factors in urological malignancies( 2014)BACKGROUND: The management of urologic cancers relies heavily on the implicit or explicit application of prognostic models. This may range from the appropriate selection of diagnostic tests based upon the pre-test probability of a positive finding, to an informed decision on choice of treatment modality or enrolment in suitable clinical trials. While some prognostic factors such as stage and grade are time-tested, others such as molecular and immunohistochemical markers or surgical approach are new and evolving. Furthermore, the literature abounds with nomograms, models, risk tables or groups which utilize varying combinations of predictor variables to prognosticate on myriad outcomes of interest. The aim of this body of work was to enhance our understanding of prognostication in urologic malignancies, particularly prostate cancer, renal cancer and urothelial cancer of the bladder, in various clinical settings. METHODS: Details of methodology vary – specifics are outlined in the relevant chapters. In general terms, an appropriate study population was defined based upon the hypothesis. Variables of interest were extracted from suitable database and / or clinical records, or assessed in the laboratory. Associations between predictors and outcomes were analysed using univariate and (where suitable) multivariate regression techniques. PRINCIPAL RESULTS: • PSA kinetics provide important prognostic information in various clinical settings, including prior to surgical treatment and after hormonal therapy • A persistently detectable PSA following radical prostatectomy is associated with a greater risk of progression and death, but with a long natural history • Younger patients with prostate cancer have less aggressive features, but a proportionately greater risk of progression and death despite curative surgical treatment • Obese patients with prostate cancer have more adverse pathologic features, but similar oncological outcomes compared to those of normal weight • A positive family history is associated with an increased risk of developing prostate cancer, but similar oncologic outcomes following surgical treatment • Gleason scoring has evolved over time, with consequent changes in the prognostic implications thereof • So-called “insignificant” prostate cancer has similar oncological outcomes to low-risk cancers overall, following surgical treatment • Patient suitability for brachytherapy as a single modality can be judged based on the clinically assessed risk of lymph node or seminal vesicle involvement • Clinical factors can predict the risk of nodal metastasis, thus allowing the rational selection of patients for pelvic lymphadenectomy at the time of radical prostatectomy • RALRP is associated with a lower rate of +SM compared to ORP, even after adjusting for known clinical and pathological risk factors • Renal cancers in solitary kidneys associated with vena caval extension may be treated by nephron-sparing surgery where technically suitable, although a high risk of disease progression and death remains • The pre-operative erythrocyte sedimentation rate provides independent prognostic information in patients with renal cancer • Renal lesions with low nephrometry score as measured using the R.E.N.A.L. have a greater likelihood of having benign or indolent histology • Histologic coagulative tumour necrosis within renal cancers is associated with poorer oncological outcomes after surgical treatment • Expression of the oncogene c-kit is rare within high-grade or sarcomatoid renal cancers • Muscle invasive urothelial cancers of the bladder are often infiltrated by profuse numbers of lymphocytes with a variety of phenotypes, although they appear not to impact on the risk of progression or death after surgical treatment • Peri-operative chemotherapy has been increasing in its use over recent years, and appears to reduce the risk of recurrence after surgical treatment of urothelial cancer of the bladder CONCLUSIONS: Many of the findings summarized above have had important implications for practice. For instance: • PSA kinetics are now in widespread use at various stages of prostate cancer management • Gleason scores from patients treated some time ago are often re-interpreted according to revised criteria