Lucianna Russo

Psychological distress in men with prostate cancer receiving adjuvant androgen-deprivation therapy

OBJECTIVES To compare the occurrence of depression, anxiety, self body image perception, sleep disturbances, and diminished quality of life in prostate cancer patients undergoing adjuvant androgen-deprivation therapy (ADT) as opposed to patients in follow-up alone. METHODS AND MATERIALS Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index, Restless Legs Syndrome Study Group essential diagnostic criteria, Body Image Scale and Functional Assessment of Cancer Therapy Prostate were administered to consecutive prostate cancer patients who underwent radical prostatectomy or radiation therapy and are presently either under adjuvant ADT or included in a follow-up program. RESULTS Of the 103 patients enrolled, 49 (47.6%) were receiving adjuvant ADT and 54 (52.4%) were not. Compared with the controls, the patients undergoing ADT showed higher levels of depression (P = 0.002), worse self body image perception (P = 0.001), worse quality of life (P = 0.0001) and worse sleep quality (P = 0.04). ADT was significantly associated with depression at multivariate analysis after adjustment for age, stage, Gleason score, as well as demographic and social variables (P = 0.001). Depression scores showed a strong inverse correlation with quality of life scores (P < 0.01). CONCLUSIONS Adjuvant ADT is associated with depression, worse quality of life, and altered self body image in prostate cancer patients.

Prognostic significance of disordered calcium metabolism in hormone-refractory prostate cancer patients with metastatic bone disease

Bone metabolic disruption that occurs in bone metastatic prostate cancer could lead to disturbances of calcium metabolism. The prognostic role of either hypocalcemia or hypercalcemia was assessed in a consecutive series of hormone-refractory bone metastatic prostate cancer patients. Serum calcium was measured in 192 patients. The presence of hypocalcemia and hypercalcemia was related with baseline biochemical and clinical characteristics and the role of these two calcium disturbances in predicting prognosis and adverse skeletal-related events (SREs) was assessed. As compared to normocalcemic patients, hypocalcemic patients (n=51) had higher tumor load in bone (P=0.005), higher plasma chromogranin A (CgA, P=0.01), serum alkaline phosphatase (P=0.01), urinary N-telopeptide (NTX, P=0.002) and lower hemoglobin values (P=0.01), while hypercalcemic patients (n=16) had higher plasma CgA (P=0.001) and serum lactate dehydrogenase values (P=0.001), higher bone pain (P=0.003) and a lower frequency of pure osteoblastic lesions (P=0.001). Hypercalcemia was significantly associated with poor prognosis: hazard ratio (HR), 1.9 (95% confidence Interval (CI) 1.2–3.3) and higher risk to develop SREs HR, 2.5 (95% CI 1.2–5.2, P=0.01), while hypocalcemia was not associated with poor prognosis. The prognostic role of hypercalcemia was maintained in multivariate analysis after adjusting for validated prognostic parameters: HR, 2.72 (95% CI 1.1–6.8, P=0.03). These data suggest that serum calcium levels should be taken into account in the clinical decision-making process of bone metastatic prostate cancer patients. Patients with asymptomatic hypercalcemia could benefit of a strict follow-up and an immediate bisphosphonate treatment. Further prospective clinical trials are needed to confirm this finding.

Trimodality treatment in the conservative management of infiltrating bladder cancer: A critical review of the literature

Although radical cystectomy is still the treatment of choice for patients with infiltrating bladder cancer, there is growing evidence of the effectiveness of a conservative approach. Developed as a treatment of need for elderly or unfit patients unable to undergo radical cystectomy, conservative therapy is becoming a true alternative to surgery for highly selected patients. Although transurethral bladder resection, external radiotherapy and systemic chemotherapy can control the disease as single treatments, the best results have been observed when they are combined. Moreover, new irradiation techniques and new-generation drugs are now being tested in an attempt to improve disease control further. Conservative management requires the multidisciplinary involvement of different specialties in order to give patients a real alternative to surgical treatment.

Prognostic role of neuroendocrine differentiation in prostate cancer, putting together the pieces of the puzzle

Neuroendocrine (NE) differentiation is a common feature in prostate cancer (PC). The clinical significance of this phenomenon is controversial; however preclinical and clinical data are in favor of an association with poor prognosis and early onset of a castrate resistant status. NE PC cells do not proliferate, but they can stimulate the proliferation of the exocrine component through the production of paracrine growth factors. The same paracrine signals may favor the outgrowth of castrate adapted tumors through androgen receptor dependent or independent mechanisms. Noteworthy, NE differentiation in PC is not a stable phenotype, being stimulated by several agents including androgen deprivation therapy, radiation therapy, and chemotherapy. The proportion of NE positive PC, therefore, is destined to increase during the natural history of the disease. This may complicate the assessment of the prognostic significance of this phenomenon. The majority of clinical studies have shown a significant correlation between NE differentiation and disease prognosis, confirming the preclinical rationale. In conclusion the NE phenotype is a prognostic parameter in PC. Whether this phenomenon is a pure prognostic factor or whether it can influence the prognosis by favoring the onset of a castrate resistance status is a matter of future research.

Why castration-resistant prostate cancer patients with neuroendocrine differentiation should be addressed to a cisplatin-based regimen

Why castration-resistant prostate cancer patients with neuroendocrine differentiation should be addressed to a cisplatinbased regimen / Vignani F; Russo L; Tucci M; Motta M; Vellani G; Tampellini M; Papotti M; Dogliotti L; Berruti A.. In: ANNALS OF ONCOLOGY. ISSN 0923-7534. 20:12(2009), pp. 2019-2020. Original Citation: Why castration-resistant prostate cancer patients with neuroendocrine differentiation should be addressed to a cisplatin-based regimen

Clinical outcomes and toxicity of estramustine phosphate (EP) addition to docetaxel (D) as first-line therapy for castration-resistant prostate cancer (CRPC): A cumulative analysis on 243 patients (pts) from two randomized phase II trials.

208 Background: Although EP exerts a synergism with D and a meta-analysis suggested a survival advantage in combining EP to chemotherapy, D+EP combination is usually discouraged due to a marginal improvement in disease control at cost of an enhanced toxicity compared to D alone. In order to assess the role of EP added to D we have analyzed data from pts enrolled in two randomized trials with D ± EP conducted by our group (BJU Int 2008 - ASCO GU 2012). METHODS All patients received D 70 mg/m2IV q 3 wks ± E 280 mg/TID PO for 5 days starting 1 day prior to D. Ninety-five pts of the first study (started in 2002) were treated until progression; 148 pts of the second study received 8 D courses in continuous or intermittent fashion. We evaluated PSA response, PFS according to PCWG2, OS and toxicity. RESULTS We shared the clinical data from all 243 pts (123 D, 120 D+EP): the median baseline PSA values were 53 and 60 respectively; 49.5% and 59.1% of the D and D+EP pts presented visceral metastases, respectively. Clinical outcomes and main toxicities are summarized in the Table. CONCLUSIONS The addition of EP to D was tolerable with a mild toxicity profile; it was able to double the biochemical responses which did not translate in any PFS or OS advantage. From our data the addition of EP addition to D should not further role in first line of CRPC, while it may help to overcome D resistance in selected cases according to our previously published data (Urol Oncol 2010). However, this statement should be critically considered at the light of new drugs availabile and active after D failure. CLINICAL TRIAL INFORMATION 2006-005728-17. [Table: see text].

Preliminary results of a factorial phase II randomized trial of continuous (C) or intermittent (I) docetaxel (DOC) with or without estramustine (E) as first-line treatment for castration-resistant prostate cancer (CRPC) (HOPLITE trial).

220 Background: DOC given for 8 consecutive courses is considered a standard first line treatment for CRPC pts and I administration could reduce its impact on quality of life (QL). E is considered synergistic with DOC. Aim of this study was to evaluate in a 2 × 2 factorial design, if I DOC could improve QL compared to C DOC and whether E added to DOC could improve its activity. METHODS CRPC pts were randomized to: C DOC 70 mg/m2 i.v. q 3 wks for 8 courses, alone (arm A) or with E 280 mg/TID p.o. for 5 days starting on -1 day (arm B), or the same treatments given with a 3-month rest period after the first 4 courses (arm C and D, respectively). The primary end points were QL (EORTC QLQ C30 and BPI) of A+B vs C+D and 1-y PFS (according to PCWG2) of A+C vs B+D. RESULTS From 11/06 to 10/10, 148 CRPC pts were enrolled and 124 pts are presently evaluable (24 too early). The median age was 69 (range 42-81) and the median baseline PSA was 55.6 (range 0.33-4212). The major hematological toxicities were: anemia G3 (3 pts), neutropenia G3 (4 pts) - G4 (5 pts), febrile neutropenia (5 pts). QL outcomes of C and I groups, were not statistically different in terms of general QL items. 1-y PFS was also superimposable (10% and 13.5%, respectively) for DOC and DOC+E groups. The 2-y overall survival was also evaluated with no differences between I and C groups (42.5% and 53.7% respectively) and between DOC and DOC+E groups (42.8% and 53.5% respectively). CONCLUSIONS These preliminary results seem to indicate that I treatment may not improve QL compared to C treatment. Moreover, the addition of E to DOC did not improve 1-y PFS of CRPC pts. Updated data with the complete sample analysis will be presented.