Symptomatic Local Progression Research Articles

Palliative surgery for metastatic prostate cancer

Androgen deprivation in combination with novel hormonal agents, docetaxel, or in combination with abiraterone/prednisone plus docetaxel or darolutamid plus docetaxel represent the standard therapeutic approach in metastatic hormone-sensitive prostate cancer (mHSPC). Patients with low-risk prostate cancer also benefit from additional radiation therapy or radical prostatectomy in terms of progression-free and overall survival. Despite favorable response rates, basically all patients will develop castration resistant prostate cancer (CRPC) within 2.5to 4years. In addition to systemic chemotherapy, second-line hormonal treatment of systemic application of radionuclides such as radium223 or 177Lu-PSMA represent salvage management options. However, nowadays about 50-65% of patients will develop symptoms due to local progression of prostate cancer which is the result of improved oncological outcomes with significantly prolonged survival times due to the new medical treatment options. Management of such symptomatic local progression will become more important in upcoming years so that all uro-oncologists need to be aware of the various surgical management options. Complications of the lower urogenital tract such as recurrent gross hematuria ± bladder clotting and with the necessity for red blood cell transfusions, subvesical obstruction and acute urinary retention, rectourethral or rectovesical fistulas might be managed by palliative surgery such as palliative transurethral resection of the prostate (TURP), radical cystectomy, radical cystoprostatectomy with urinary diversion, and pelvic exenteration. Symptomatic or asymptomatic obstruction of the upper urinary tract might be managed by endoluminal or percutaneous urinary diversion, ureteral reimplantation, ileal ureter replacement, or implantation of the Detour® system (Coloplast GmbH, Hamburg, Germany).

Palliative urologic surgery for metastatic prostate cancer: what needs to be considered in the future?

Androgen deprivation in combination with novel hormonal agents, docetaxel or the combination of abiraterone/prednisone plus docetaxel or darolutamide plus docetaxel represent the standard therapeutic approach in metastatic hormone-sensitive prostate cancer (mHSPC). Patients with low-risk prostate cancer also benefit from additional radiation therapy or radical prostatectomy in terms of progression-free and overall survival. Despite favourable response rates, basically all patients will develop castration-resistant prostate cancer (CRPC) within 2.5 to 4 years. Systemic chemotherapy, second-line hormonal treatment or systemic application of radionuclides such as Radium-223 or 177Lu-PSMA represent salvage management options. As the new medical treatment options have led to an improved oncological outcome with significantly prolonged survival times, about 50% to 65% of patients will develop symptoms due to local progression of prostate cancer. The management of such symptomatic local progression will become more important in upcoming years, which means that all uro-oncologists need to be aware of the various surgical management options. If complications of the lower urogenital tract occur, for example repetitive gross haematuria with or without bladder clotting and with the necessity for red blood cell transfusions, subvesical obstruction, acute urinary retention or rectourethral or rectovesical fistulas, these may be managed by palliative surgery such as palliative TURP, radical cystectomy, radical cystoprostatectomy with urinary diversion, and pelvic exenteration. Symptomatic or asymptomatic obstruction of the upper urinary tract can be managed by endoluminal or percutaneous urinary diversion, ureteral reimplantation, ileal ureter replacement, or implantation of a Detour system. However, an individualised and risk-adapted treatment strategy needs to be developed for each single patient to achieve an optimal therapeutic outcome with improvement of both symptoms and quality of life. In specific clinical situations, best supportive care may be an adequate option.

Change in Blood Counts after Palliative Radiotherapy for Multiple Myeloma

Radiation therapy (RT) can provide effective palliation and prevent symptomatic local progression of multiple myeloma (MM). However, RT is sometimes avoided due to concerns for secondary impact to bone marrow, potentially decreasing blood cell counts and precluding ability to receive future systemic therapies. We reviewed a series of MM patients who received palliative RT to assess changes in blood counts from pre-RT to post-RT, hypothesizing that blood counts would not significantly decline after treatment with modern RT volumes and techniques. We utilized a prospectively maintained departmental database and included patients who received palliative RT for MM from 2015 to 2020. Lab values immediately pre-RT (within one month of RT start date) and post-RT (within three months of RT completion) including hemoglobin, lymphocytes, neutrophils, and platelets were collected. Statistical differences from pre-RT to post-RT were assessed using t-tests. ANOVA was used to compare change in blood counts between common dose fractionation regimens (30 Gy in 10 Fractions, 20 Gy in 5, and 8 Gy in 1). A total of 334 MM patients receiving 424 courses of RT were included in this analysis. The median age at start of first treatment was 67 (IQR: 60-76) years. One-hundred ninety-five (58%) were male. Median RT dose was 20 (IQR: 8-24.5) Gy delivered over a median 5 (IQR: 1-5) fractions. Between pre-RT and post-RT, there was no significant change in hemoglobin (+0.1 g/dL (IQR: -0.8, +0.5), p = .076), lymphocyte counts (-0.3*10^9 cells/L (IQR: -0.6, 0), p = .435), or neutrophil counts (-0.1*10^9 cells/L (IQR: -1.1, +0.9), p = .310). In contrast, platelet counts significantly decreased from pre-RT (median 165*10^9 cells/L, IQR: 112-210) to post-RT (median 146, IQR: 93-194) by a median of 17.5 *10^9 cells/L (IQR: -52.5, +14.0, p<0.0001). There were no differences in changes in hemoglobin, neutrophils, or platelets between the common dose fractionations. However, there was a significantly greater drop in lymphocytes after 30 Gy in 10 fractions (p = .039, mean lymphocyte count change (in 10^9 cells/L) for 30 Gy in 10: -0.87, 20 Gy in 5: -0.47, and 8 Gy in 1: -0.27). In this large dataset of patients receiving modern palliative RT for MM, hemoglobin, lymphocytes, and neutrophils did not significantly decline from pre-RT to post-RT. In contrast, there was a statistically significant drop in platelet count by a median 17.5*10^9 cells/L from pre-RT to post-RT, which may or may not be clinically significant depending on clinical context. Patients receiving 30 Gy in 10 fractions had greater drops in lymphocytes than those receiving lower doses. Further analyses will be performed to determine clinical, dosimetric, and volumetric predictors of decline in blood counts after radiation.

Radiotherapy as a Bridging Approach in High-Grade B-Cell Lymphomas before CD19-Targeted CAR T-Cell Therapy

<h3>Purpose/Objective(s)</h3> To evaluate the safety and efficacy of bridging radiation therapy (RT) in patients with relapsed/refractory high-grade B cell lymphomas (HGBCL) undergoing CD19-targeted chimeric antigen receptor (CAR) T-cell therapy. <h3>Materials/Methods</h3> A multi-institutional retrospective study was performed for 352 patients with HGBCL treated with CAR T-cell therapy. 140 of 352 patients (40%) received bridging therapy prior to CAR T infusion: systemic therapy alone in 98 patients, and RT +/- systemic therapy in 42 patients. This report focuses on the outcome of the 42 patients who received bridging RT. Overall survival (OS) from the date of CAR T infusion was estimated with the Kaplan-Meier method. The time to in-field progression was defined as the time from the start date of bridging RT until the time of in-field progression. <h3>Results</h3> The median follow-up from the date of CAR T infusion was 5.2 months (range, 9 days-33.6 months). Thirty-four patients (81%) received RT within 30 days of CAR T infusion, while 8 patients (19%) received RT at least 30 days before infusion. The most common indication for bridging RT was symptomatic local progression, with 16 patients starting RT prior to apheresis due to clinical urgency. Sites of RT include: head and neck (12), central nervous system (8), chest (5), pelvis (5), abdomen (4), extremities (2), paraspinal area (3), and multiple sites (3). The median dose/fractionation were 24 Gy (range, 8-37.5 Gy) and 8 fractions (range, 2-15 fractions). Three patients (7%) had in-field progression at a median time of 3.2 months (range, 1.2-4.6 months), all of whom had bulky disease (≥5 cm) at the time of apheresis. Superior median OS was observed among the 38 patients (90%) who achieved objective in-field responses after bridging-RT (25.6 months vs. 2.1 months; p=<0.001). Only 2 patients experienced grade 3-4 RT-related toxicities. <h3>Conclusion</h3> Our data supports that RT is an effective bridging approach for patients with locally progressive HGBCL prior to CAR T-cell therapy. It is associated with limited toxicity, and offers excellent in-field control in the immediate post-CAR T timeframe. Patients with in-field response to bridging RT have significantly better survival outcome.

Radical cytoreductive prostatectomy in men with prostate cancer and oligometastatic disease.

Local treatment of the primary by either radical prostatectomy or radiation therapy is discussed controversially. The role of cytoreductive radical prostatectomy has been evaluated in few retrospective clinical studies but data of prospective randomized clinical phase-III trials are lacking. It is the purpose of this review to reflect the current knowledge on indication, functional and oncological outcomes of cytoreductive radical prostatectomy to objectively highlight what can be expected from this approach. Cytoreductive radical prostatectomy (cRP) is associated with a long overall survival of more than 7 years and it is associated with a clinical progression-free survival of more than 6 years. When compared with nonsurgical approaches it becomes evident that about one-third of the patients will develop symptomatic local progression within 3 years whereas none of the surgically treated patients will experience such symptoms. cRP is associated with a low rate of significant complications and good functional outcome in well selected patients which do not differ from the results of a radical prostatectomy in treatment-naïve patients. Patients with low-volume/low-risk metastatic prostate cancer (mPCA), good response to neoadjuvant androgen deprivation therapy and a good Eastern Cooperative Onology Group performance status appear to be the best candidates for surgery. cRP might be an individualized treatment option in the multimodality management of mPCA. It is the purpose of the current to highlight the indication, surgical technique, treatment associated complications, functional and oncological outcome for cytoreductive radical prostatectomy.

Role of surgery in oligometastatic prostate cancer.

Androgen deprivation therapy as single modality therapy was the standard management for oligometastatic prostate cancer (PCa). Current paradigm shifts toward a multimodality therapy approach, targeting all sites of disease, including treatment of the primary in the form of radical prostatectomy or radiation therapy. The objective of this article was to reveiw the literature regarding the role of surgery in oligometastatic PCa. PubMed and MEDLINE electronic databases were queried for English language articles from January 1, 1980 to March 31, 2019. Keywords use included oligometastatic PCa, metastatic prostate cancer (mPCa), radical prostatectomy, and cytoreductive prostatectomy. Preclinical, prospective, and retrospective studies were included. There is no published randomized controlled trials, evaluating the role of surgery in mPCa. Preclinical and retrospective data suggest benefit of primary tumor treatment in mPCa. Current literature supports the concept of cytoreductive surgery as it can prevent late symptomatic local progression, has acceptable complications, and may prolong survival in patients with mPCa. Surgery is a feasible procedure in mPCa which may improve outcome in mPCa. However, there is no Level 1 evidence, yet that support the role of surgery in mPCa. The results from well-organized prospective, randomized controlled trials are awaited before performing radical prostatectomy for mPCa in clinical practice.

Radiation therapy for the management of patients with HTLV-1–associated adult T-cell leukemia/lymphoma

AbstractHuman T-cell leukemia virus type 1–associated adult T-cell leukemia/lymphoma (ATL) typically has survivals measured in months with chemotherapy. One prior published series (1983-1991) assessed local radiotherapy for ATL. Ten consecutive patients with pathologically confirmed ATL treated with radiotherapy were reviewed. Subtypes included acute (n = 7), smoldering (n = 2), and lymphomatous (n = 1). Patients received an average of 2.5 systemic therapy regimens before radiotherapy. Twenty lesions (cutaneous = 10, nodal = 8, extranodal = 2) were treated to a mean of 35.4 Gy/2-3 Gy (range, 12-60 Gy). At 9.0-month mean follow-up (range, 0.1-42.0 months), all lesions symptomatically and radiographically responded, with in-field complete responses in 40.0% (nodal 37.5% vs cutaneous 50.0%; P = .62). No patient experienced in-field progression. Nine patients developed new/progressive out-of-field disease. Median survival was 17.0 months (3-year survival, 30.0%). No Radiation Therapy Oncology Group acute grade ≥ 3 or any late toxicity was noted. This report is the first to use modern radiotherapy techniques and finds effective local control across ATL subtypes. Radiotherapy should be considered for symptomatic local progression of ATL.

Excision of the Primary Tumour in Patients with Metastatic Breast Cancer: A Clinical Dilemma

Approximately 10% of new breast cancer patients will present with overt synchronous metastatic disease. The optimal local management of those patients is controversial. Several series suggest that removal of the primary tumour is associated with a survival benefit, but the retrospective nature of those studies raises considerable methodologic challenges. We evaluated our clinical experience with the management of such patients and, more specifically, the impact of surgery in patients with synchronous metastasis. We reviewed patients with primary breast cancer and concurrent distant metastases seen at our centre between 2005 and 2007. Demographic and treatment data were collected. Study endpoints included overall survival and symptomatic local progression rates. The 111 patients identified had a median follow-up of 40 months (range: 0.6-71 months). We allocated the patients to one ot two groups: a nonsurgical group (those who did not have breast surgery, n = 63) and a surgical group (those who did have surgery, n = 48, 29 of whom had surgery before the metastatic diagnosis). When compared with patients in the nonsurgical group, patients in the surgical group were less likely to present with T4 tumours (23% vs. 35%), N3 nodal disease (8% vs. 19%), and visceral metastasis (67% vs. 73%). Patients in the surgical group experienced longer overall survival (49 months vs. 33 months, p = 0.01) and lower rates of symptomatic local progression (14% vs. 44%, p < 0.001). In our study, improved overall survival and symptomatic local control were demonstrated in the surgically treated patients; however, this group had less aggressive disease at presentation. The optimal local management of patients with metastatic breast cancer remains unknown. An ongoing phase iii trial, E2108, has been designed to assess the effect of breast surgery in metastatic patients responding to first-line systemic therapy. If excision of the primary tumour is associated with a survival benefit, then the preselected subgroup of patients who have responded to initial systemic therapy is the desired population in which to put this hypothesis to the test.

P2-15-05: Excision of the Primary Tumour in Patients with Metastatic Breast Cancer – Will E2108 Provide the Definitive Answer?

Abstract Background: Approximately 10% of new breast cancer patients will present with overt synchronous metastatic disease. Controversy exists about the optimal local management of these patients. While several series suggest that removal of primary tumour is associated with a survival benefit, the retrospective nature of these studies raises considerable methodological challenges. We decided to evaluate the experience at our centre around the impact of surgery in patients with synchronous metastasis. Method: Case records of all patients seen with primary breast cancer and concurrent distant metastases between 2005 to 2007 were reviewed. Demographic and treatment data was collected. The study endpoints compared both overall survival and symptomatic local progression rates between patients who had breast surgery and those who did not. RESULTS: 111 patients were identified. Median follow-up 40 months (0.6-71 months). Patients were divided into two groups: those patients who underwent breast surgery (n=48; 29/48 had surgery immediate prior to metastatic diagnosis) and those that did not have surgery(n = 63). The surgical group were less likely to present with T4 tumours (20% vs 36%), N3 nodal disease (8% vs 19%) and visceral metastasis (67% vs 73%)when compared with non-surgical group. Improved overall survival (49 months vs 33 months; p=0.01) and less symptomatic local progression rates ( 15% vs 43%, p &amp;lt; 0.001 ) were seen in the surgical group compared to the non-surgical group. CONCLUSIONS: The optimal local management of patients with metastatic breast cancer is unknown. Despite the surgery group demonstrating an improved overall survival and symptomatic local control, this group had less aggressive disease at presentation. These results confirm the need for prospective randomized studies. E2108, an ongoing Phase III Trial, was designed to assess the effect of breast surgery in metastatic patients responding to first line systemic therapy. If excision of the primary tumour is associated with a survival benefit, then the pre-selected subgroup of patients that have responded to initial systemic therapy is the desired population to put this hypothesis to test. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-15-05.

Surgical management of lymph‐node‐positive prostate cancer: improves symptomatic control

Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? There is a paucity of data regarding symptomatic local progression of patients treated with radical prostatectomy in the setting of lymph-node-positive prostate cancer. Our retrospective study shows that radical prostatectomy with adjuvant hormonal therapy improves local control of patients in this cohort. • To assess the impact of primary surgical therapy on local control for patients with lymph-node-positive prostate cancer. • A retrospective analysis from January 1982 to January 2001 identified 192 patients treated by radical retropubic prostatectomy (RRP, N= 87), hormonal ablative therapy (ADT, N= 74), or RRP plus adjuvant hormones (RRP + ADT, N= 31). • Statistical analyses were conducted using the Kruskal-Wallis test, chi-squared or Fisher's exact test, log-rank test and logistic regression with the statistical significance level set at P < 0.05. • The incidence of local relapse in the three treatment groups (RRP, ADT and RRP + ADT) was 40.2%, 59.5% and 12.9%, respectively. • Among those with local relapse, the incidence of symptomatic local relapse (defined as local symptoms secondary to locally recurrent prostate cancer) was 25.7%, 75.0% and 50.0%, respectively. • Logistic regression analysis used to identify predictors of local relapse indicated that patients treated with ADT (OR = 1.96; P= 0.270) had higher odds of having a local relapse whereas patients treated with RRP + ADT (OR = 0.20; P= 0.032) had significantly lower odds of having a local relapse compared with patients treated with RRP (reference group) after adjusting for other significant predictors such as increases in serum PSA at diagnosis (OR = 1.09; P= 0.018) and biochemical failure after primary therapy (OR = 48.3; P < 0.001). • Logistic regression analysis used to identify predictors of symptomatic local relapse, among patients having had a relapse, indicated that patients treated with RRP + ADT (OR = 2.90; P= 0.322) had higher odds of having a symptomatic local relapse whereas patients treated with ADT alone (OR = 8.67; P < 0.001) had significantly higher odds of having a symptomatic local relapse compared with patients treated with RRP (reference group). • Radical prostatectomy (with adjuvant hormonal therapy) provides improved local control in patients with lymph-node-positive prostate cancer. • This important endpoint must be considered when determining the optimal treatment of patients with node-positive disease.

Evidence-Based Medicine, Conscience-Based Medicine, and the Management of Low-Risk Prostate Cancer

Evidence-Based Medicine, Conscience-Based Medicine, and the Management of Low-Risk Prostate Cancer

Update on the management of prostate cancer with goserelin acetate: patient perspectives

The guidelines for the use of androgen deprivation therapy (ADT) have changed significantly over the last 5 years. This paper reviews the current recommendations and documents the reasons for these changes, in a review of the world's literature on ADT over the last 5 years. Special emphasis on randomized controlled trials and high-impact journals was included in the Medline search and review. One hundred articles on this topic written in the last 5 years were reviewed. Fifty-nine contained nonindustry-biased findings in major-impact journals and were available in English. The benefits of ADT are evident in several areas, including neoadjuvantly and adjuvantly in patients treated with external beam radiation therapy for intermediate- and high-risk disease; in patients who have undergone prostatectomy and who are found to have lymph node involvement on surgical resection; in high-risk patients after definitive therapy; and in patients who have developed symptomatic local progression or metastasis. This paper reviews the risks and benefits in each of these scenarios and the risks of androgen deprivation in general, and delineates the areas where ADT was previously recommended, but has been found to no longer be of benefit.

Radiosensitization of Chemotherapy-Refractory, Locally Advanced or Locally Recurrent Breast Cancer With Trastuzumab: A Phase II Trial

Trastuzumab (Herceptin), an anti-human epidermal growth factor receptor 2 (HER2) antibody, has been shown to be an effective radiosensitizer in preclinical studies. The present Phase II trial evaluated trastuzumab plus radiotherapy in patients with HER2-positive, chemotherapy-refractory, locally advanced or locoregionally recurrent breast cancer. Eligible patients had measurable disease, normal cardiac function, and biopsy-confirmed residual HER2-positive disease. Patients received weekly trastuzumab (2 mg/kg intravenously), concurrent with radiotherapy (50 Gy) to the breast and regional lymph nodes for 5 weeks. If feasible, surgery followed radiotherapy. The primary endpoint was safety, and the secondary endpoint was efficacy (pathologic response and interval to symptomatic local progression). Of the 19 patients enrolled, 7 were ineligible and received radiotherapy alone and 12 received therapy per protocol. Of these 12 patients, 11 had a Stage T4 diagnosis. Grade 3 toxicities included skin (n = 2) and lymphopenia (n = 1). One patient experienced delayed wound healing after surgery. No patients developed symptomatic cardiac dysfunction. Of the 7 patients who had undergone mastectomy, 3 (43%) had a substantial pathologic response (complete response or microscopic residual disease), significantly more than a comparison cohort (2 of 38 or 5%, p = .02). The median interval to symptomatic local progression was not reached. The median overall survival was 39 months. This is the first prospective trial providing evidence for a radiosensitizing effect of trastuzumab in breast cancer. The combination of trastuzumab and radiotherapy was well tolerated.